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acrac_69443_0

Suspected Physical Abuse Child

Introduction/Background Based on reports to child and protective service agencies, an estimated 3.2 million children were investigated for maltreatment (neglect, emotional abuse, sexual abuse, and physical abuse) in the United States in 2013, and an estimated 679,000 (9.1/1000 children) were victims of abuse [1]. The youngest children are most vulnerable; children in their first year of life had the highest rate of victimization at 23.1/1000. An estimated 1520 children died from abuse, with three-fourths of these under 3 years of age. However, the full extent of child abuse is not known because of underreporting [2,3]. Overview of Imaging Modalities X-ray skeletal survey The radiographic skeletal survey is the primary imaging examination for detecting fractures [11]. The skeletal survey should be composed of frontal and lateral views of the skull, lateral views of the cervical spine and thoracolumbosacral spine, and single frontal views of the long bones, hands, feet, chest, and abdomen. Oblique views of the ribs should be obtained to increase the accuracy of diagnosing rib fractures [12,13], which are strong positive predictors and may be the only skeletal manifestation of abuse [14,15]. The images should be obtained using high-detail imaging systems and coned to the specific area of interest for each of the body parts, with separate views of each arm, forearm, thigh, leg, hand, and foot to improve image quality and diagnostic accuracy [16] (see Appendix 1). Fractures most often involve the long bones and ribs, with lesser involvement of the skull and clavicles and even less frequent involvement of the pelvis, spine, hands, and feet [17]. It has therefore been questioned whether the radiation exposure outweighs the potential benefit of imaging the pelvis, spine, hands, and feet on initial skeletal survey [17-20]. Although not part of American Reprint requests to: [email protected]

Suspected Physical Abuse Child. Introduction/Background Based on reports to child and protective service agencies, an estimated 3.2 million children were investigated for maltreatment (neglect, emotional abuse, sexual abuse, and physical abuse) in the United States in 2013, and an estimated 679,000 (9.1/1000 children) were victims of abuse [1]. The youngest children are most vulnerable; children in their first year of life had the highest rate of victimization at 23.1/1000. An estimated 1520 children died from abuse, with three-fourths of these under 3 years of age. However, the full extent of child abuse is not known because of underreporting [2,3]. Overview of Imaging Modalities X-ray skeletal survey The radiographic skeletal survey is the primary imaging examination for detecting fractures [11]. The skeletal survey should be composed of frontal and lateral views of the skull, lateral views of the cervical spine and thoracolumbosacral spine, and single frontal views of the long bones, hands, feet, chest, and abdomen. Oblique views of the ribs should be obtained to increase the accuracy of diagnosing rib fractures [12,13], which are strong positive predictors and may be the only skeletal manifestation of abuse [14,15]. The images should be obtained using high-detail imaging systems and coned to the specific area of interest for each of the body parts, with separate views of each arm, forearm, thigh, leg, hand, and foot to improve image quality and diagnostic accuracy [16] (see Appendix 1). Fractures most often involve the long bones and ribs, with lesser involvement of the skull and clavicles and even less frequent involvement of the pelvis, spine, hands, and feet [17]. It has therefore been questioned whether the radiation exposure outweighs the potential benefit of imaging the pelvis, spine, hands, and feet on initial skeletal survey [17-20]. Although not part of American Reprint requests to: [email protected]

69443

acrac_69443_1

Suspected Physical Abuse Child

College of Radiology (ACR) or American Academy of Pediatrics guidelines, some add lateral radiographs of the long bones, which have been shown to increase detection of metaphyseal fractures by 50% [21]. A repeat skeletal survey performed approximately 2 weeks after the initial examination can provide additional information on the presence and age of child abuse fractures [22] in up to 12% of children and should be performed when abnormal or equivocal findings are found on the initial study and when abuse is suspected on clinical grounds [23]. To limit radiation exposure, pelvis, spine, and skull radiographs can be omitted if no injury was initially seen in these regions [24-26]. However, it is not possible to exactly date fractures by radiography [27]. Tc-99m bone scan whole body In experienced hands, bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries [28,29] but is usually not considered an alternative to skeletal survey. It should be used when the radiographic skeletal survey is negative but clinical suspicion remains high and a search for further evidence of skeletal trauma is warranted. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs, but it requires venipuncture and often requires sedation. In addition to standard images, the use of pinhole collimators [29] and differential counts of the metaphyses may improve sensitivity. A bone scan is especially good for detecting periosteal reaction and rib, spine, pelvic, and acromion fractures [23,30]. However, skull fractures and fractures near the growth plates, because of normally increased activity in the growth plate, may be difficult to appreciate [31,32]. Bone scan is also not useful in dating of fractures, as the scan may be active for up to a year after injury [29]. CT head without contrast Unenhanced computed tomography (CT) of the head is the examination of choice to evaluate children with suspected abusive head trauma (AHT) [33].

Suspected Physical Abuse Child. College of Radiology (ACR) or American Academy of Pediatrics guidelines, some add lateral radiographs of the long bones, which have been shown to increase detection of metaphyseal fractures by 50% [21]. A repeat skeletal survey performed approximately 2 weeks after the initial examination can provide additional information on the presence and age of child abuse fractures [22] in up to 12% of children and should be performed when abnormal or equivocal findings are found on the initial study and when abuse is suspected on clinical grounds [23]. To limit radiation exposure, pelvis, spine, and skull radiographs can be omitted if no injury was initially seen in these regions [24-26]. However, it is not possible to exactly date fractures by radiography [27]. Tc-99m bone scan whole body In experienced hands, bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries [28,29] but is usually not considered an alternative to skeletal survey. It should be used when the radiographic skeletal survey is negative but clinical suspicion remains high and a search for further evidence of skeletal trauma is warranted. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs, but it requires venipuncture and often requires sedation. In addition to standard images, the use of pinhole collimators [29] and differential counts of the metaphyses may improve sensitivity. A bone scan is especially good for detecting periosteal reaction and rib, spine, pelvic, and acromion fractures [23,30]. However, skull fractures and fractures near the growth plates, because of normally increased activity in the growth plate, may be difficult to appreciate [31,32]. Bone scan is also not useful in dating of fractures, as the scan may be active for up to a year after injury [29]. CT head without contrast Unenhanced computed tomography (CT) of the head is the examination of choice to evaluate children with suspected abusive head trauma (AHT) [33].

69443

acrac_69443_2

Suspected Physical Abuse Child

These include children who had skeletal survey for suspected child abuse, children with neurological changes, and children with facial injuries raising concern for abuse. Multiplanar reformations and 3-D volume rendering of the skull increase sensitivity for fracture and intracranial hemorrhage [34,35]. MRI head without contrast Magnetic resonance imaging (MRI) is sensitive for the detection of small-volume extra-axial hemorrhage and for evolving parenchymal injury [36]. In addition to standard sequences, diffusion-weighted imaging and susceptibility-weighted imaging increase sensitivity for detection of parenchymal ischemia, diffuse axonal injury, and microhemorrhage and can provide prognostic information in AHT. The addition of contrast-enhanced MRI sequences can be used in select cases to improve evaluation of extra-axial collections [37] as it increases the sensitivity for the detection of membranes in subdural collections, a finding that indicates a chronic component [37]. Care must be taken when attempting to date subdural collections, however, as the imaging appearance depends not just on the age of blood products but also on the potential presence of cerebrospinal fluid accumulation in the subdural space through an arachnoid laceration (hematohygroma) [38]. Thrombosis of bridging veins in the subdural space also suggest abusive trauma [39,40]. The MRI should include T1- and T2-weighted imaging as well as T2 FLAIR and T2* (gradient-echo or susceptibility-weighted imaging) sequences. Diffusion-weighted sequences are required to indicate whether acute cerebral injury is present [36]. Susceptibility-weighted imaging may be useful in detection of blood products in the brain as well as retinal hemorrhages [41,42]. MRI is a particularly good choice to image children at high risk for AHT in the nonemergent setting but is a lengthy scan often requiring sedation, so it is typically not utilized in the emergent setting.

Suspected Physical Abuse Child. These include children who had skeletal survey for suspected child abuse, children with neurological changes, and children with facial injuries raising concern for abuse. Multiplanar reformations and 3-D volume rendering of the skull increase sensitivity for fracture and intracranial hemorrhage [34,35]. MRI head without contrast Magnetic resonance imaging (MRI) is sensitive for the detection of small-volume extra-axial hemorrhage and for evolving parenchymal injury [36]. In addition to standard sequences, diffusion-weighted imaging and susceptibility-weighted imaging increase sensitivity for detection of parenchymal ischemia, diffuse axonal injury, and microhemorrhage and can provide prognostic information in AHT. The addition of contrast-enhanced MRI sequences can be used in select cases to improve evaluation of extra-axial collections [37] as it increases the sensitivity for the detection of membranes in subdural collections, a finding that indicates a chronic component [37]. Care must be taken when attempting to date subdural collections, however, as the imaging appearance depends not just on the age of blood products but also on the potential presence of cerebrospinal fluid accumulation in the subdural space through an arachnoid laceration (hematohygroma) [38]. Thrombosis of bridging veins in the subdural space also suggest abusive trauma [39,40]. The MRI should include T1- and T2-weighted imaging as well as T2 FLAIR and T2* (gradient-echo or susceptibility-weighted imaging) sequences. Diffusion-weighted sequences are required to indicate whether acute cerebral injury is present [36]. Susceptibility-weighted imaging may be useful in detection of blood products in the brain as well as retinal hemorrhages [41,42]. MRI is a particularly good choice to image children at high risk for AHT in the nonemergent setting but is a lengthy scan often requiring sedation, so it is typically not utilized in the emergent setting.

69443

acrac_69443_3

Suspected Physical Abuse Child

MRI spine Recent evidence supports that spine injury is common in children with AHT. In recent retrospective studies [43- 45], ligamentous injury at the craniocervical junction and spinal subdural hemorrhage (SDH) are reported in 36% to 78% and 44% to 63% of AHT cases, respectively. MRI of the cervical spine, including fat-suppressed fluid- sensitive sequences, a sagittal short tau inversion recovery or T2 fat-saturated sequence, should be performed in all cases where the skeletal survey demonstrates any fractures or when clinical concern for craniocervical junction or spinal injury is high. The prevalence of spine fracture is increased to almost 10% in the setting of a positive skeletal survey and is significantly associated with intracranial injury [18]. The high incidence of cervical injuries in abused children with bilateral hypoxic-ischemic brain injuries suggests a causal relationship [44]. The value of routine screening of the whole spine in suspected AHT is still debated. In a subgroup of 38 children with AHT who underwent thoracolumbar spine imaging, 24 (63%) had thoracolumbar SDH, whereas only 1 of 70 patients with accidental trauma had spinal SDH in the same study [43]. None of the children had spinal cord compression or long-term complications from the presence of the spinal SDH, and that imaging was performed mostly because of concern for thoracic or abdominal injury. Although not usually prompting change in management, detection of spinal SDH is significantly increased when imaging is extended through the thoracolumbar spine [45]. The presence of thoracolumbar SDH does not imply direct trauma to the thoracolumbar spine and may be related to redistribution of blood products. Nevertheless, this finding has medicolegal implications as it may document otherwise undetected injury and may help distinguish between abusive and accidental injury.

Suspected Physical Abuse Child. MRI spine Recent evidence supports that spine injury is common in children with AHT. In recent retrospective studies [43- 45], ligamentous injury at the craniocervical junction and spinal subdural hemorrhage (SDH) are reported in 36% to 78% and 44% to 63% of AHT cases, respectively. MRI of the cervical spine, including fat-suppressed fluid- sensitive sequences, a sagittal short tau inversion recovery or T2 fat-saturated sequence, should be performed in all cases where the skeletal survey demonstrates any fractures or when clinical concern for craniocervical junction or spinal injury is high. The prevalence of spine fracture is increased to almost 10% in the setting of a positive skeletal survey and is significantly associated with intracranial injury [18]. The high incidence of cervical injuries in abused children with bilateral hypoxic-ischemic brain injuries suggests a causal relationship [44]. The value of routine screening of the whole spine in suspected AHT is still debated. In a subgroup of 38 children with AHT who underwent thoracolumbar spine imaging, 24 (63%) had thoracolumbar SDH, whereas only 1 of 70 patients with accidental trauma had spinal SDH in the same study [43]. None of the children had spinal cord compression or long-term complications from the presence of the spinal SDH, and that imaging was performed mostly because of concern for thoracic or abdominal injury. Although not usually prompting change in management, detection of spinal SDH is significantly increased when imaging is extended through the thoracolumbar spine [45]. The presence of thoracolumbar SDH does not imply direct trauma to the thoracolumbar spine and may be related to redistribution of blood products. Nevertheless, this finding has medicolegal implications as it may document otherwise undetected injury and may help distinguish between abusive and accidental injury.

69443

acrac_69443_4

Suspected Physical Abuse Child

CT chest without contrast CT of the chest is more sensitive than chest radiography in detection of rib fractures; chest radiography defines only about 60% of the fractures that are detected by CT [46]. Anterior and posterior fractures are better seen by CT, as are bilateral fractures. However, the need for sedation in noncooperative children makes this test a useful adjunct rather than a first-line test in the imaging workup of nonaccidental trauma (NAT). A reduced-dose chest CT may detect rib fractures in infants with high suspicion for NAT and a normal initial 4-view chest, with a sub- millisievert radiation dose equaling twice that of a 4-view chest [47]. Multiplanar reformatted images may aid in rib fracture detection [48]. In addition, chest CT may detect scapular and spine fractures not evident on skeletal survey [47]. CT chest with contrast A CT scan of the chest with intravenous (IV) contrast is reserved for children with clinical suspicion of intrathoracic traumatic injury. IV contrast allows for detection of vascular injuries. CT abdomen and pelvis with contrast CT of the abdomen and pelvis with IV contrast is utilized for children with suspected intra-abdominal and/or intrapelvic injury [49]. Portal venous phase imaging is most helpful for detecting solid-organ injury. Delayed excretory-phase imaging may be useful in a few selected cases when imaging findings suggest disruption of the genitourinary tract. Noncontrast abdominal CT is not recommended. The need for oral contrast is at the discretion of the radiologist, and its use may be considered when there is concern for duodenal hematoma [23]. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries [28,29] but is usually not considered an alternative to skeletal survey. It should be used when the radiographic skeletal survey is negative but clinical suspicion remains high and search for further evidence of skeletal trauma is warranted.

Suspected Physical Abuse Child. CT chest without contrast CT of the chest is more sensitive than chest radiography in detection of rib fractures; chest radiography defines only about 60% of the fractures that are detected by CT [46]. Anterior and posterior fractures are better seen by CT, as are bilateral fractures. However, the need for sedation in noncooperative children makes this test a useful adjunct rather than a first-line test in the imaging workup of nonaccidental trauma (NAT). A reduced-dose chest CT may detect rib fractures in infants with high suspicion for NAT and a normal initial 4-view chest, with a sub- millisievert radiation dose equaling twice that of a 4-view chest [47]. Multiplanar reformatted images may aid in rib fracture detection [48]. In addition, chest CT may detect scapular and spine fractures not evident on skeletal survey [47]. CT chest with contrast A CT scan of the chest with intravenous (IV) contrast is reserved for children with clinical suspicion of intrathoracic traumatic injury. IV contrast allows for detection of vascular injuries. CT abdomen and pelvis with contrast CT of the abdomen and pelvis with IV contrast is utilized for children with suspected intra-abdominal and/or intrapelvic injury [49]. Portal venous phase imaging is most helpful for detecting solid-organ injury. Delayed excretory-phase imaging may be useful in a few selected cases when imaging findings suggest disruption of the genitourinary tract. Noncontrast abdominal CT is not recommended. The need for oral contrast is at the discretion of the radiologist, and its use may be considered when there is concern for duodenal hematoma [23]. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries [28,29] but is usually not considered an alternative to skeletal survey. It should be used when the radiographic skeletal survey is negative but clinical suspicion remains high and search for further evidence of skeletal trauma is warranted.

69443

acrac_69443_5

Suspected Physical Abuse Child

It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs, but it requires venipuncture and often requires sedation. CT head and MRI head There are varying opinions on how to image suspected abuse victims who show no evidence suggesting intracranial injury. Although skull radiographs may detect fractures associated with intracranial pathology, they do not provide adequate screening, since significant traumatic intracranial pathology may occur in the absence of skull fractures [58,59]. Children, especially those <12 months of age, may have significant intracranial injury without signs or symptoms of head injury or retinal hemorrhage [60-62]. Unenhanced CT of the head is the examination of choice for initial evaluation for intracranial injury in child abuse [33]. MRI is a good choice to image children for abusive head injury in the nonemergent setting. A study of abused children without clinical suspicion of intracranial injury showed that 11 (29%) of the 51 children had positive neuroimaging including subdural hematoma, epidural hematoma, or cerebral edema; most of them had negative skeletal surveys and no retinal hemorrhage. Eight of the 11 children were <12 months of age [60]. In another prospective study of infants <6 months of age evaluated for possible physical abuse, the presence of apparently isolated bruises (seen in 146 children) at presentation correlated with new injury on neuroimaging in 40 children (27%) [50]. In yet another study [61], 37% of children <2 years of age with high-risk criteria (defined as rib fractures, multiple fractures, facial injury, or <6 months of age) and without overt signs of head injury who underwent head CT or MRI had occult head injury; nearly all with occult head injury were <1 year of age. Intracranial injury is also associated with spinal trauma seen on skeletal survey [18].

Suspected Physical Abuse Child. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs, but it requires venipuncture and often requires sedation. CT head and MRI head There are varying opinions on how to image suspected abuse victims who show no evidence suggesting intracranial injury. Although skull radiographs may detect fractures associated with intracranial pathology, they do not provide adequate screening, since significant traumatic intracranial pathology may occur in the absence of skull fractures [58,59]. Children, especially those <12 months of age, may have significant intracranial injury without signs or symptoms of head injury or retinal hemorrhage [60-62]. Unenhanced CT of the head is the examination of choice for initial evaluation for intracranial injury in child abuse [33]. MRI is a good choice to image children for abusive head injury in the nonemergent setting. A study of abused children without clinical suspicion of intracranial injury showed that 11 (29%) of the 51 children had positive neuroimaging including subdural hematoma, epidural hematoma, or cerebral edema; most of them had negative skeletal surveys and no retinal hemorrhage. Eight of the 11 children were <12 months of age [60]. In another prospective study of infants <6 months of age evaluated for possible physical abuse, the presence of apparently isolated bruises (seen in 146 children) at presentation correlated with new injury on neuroimaging in 40 children (27%) [50]. In yet another study [61], 37% of children <2 years of age with high-risk criteria (defined as rib fractures, multiple fractures, facial injury, or <6 months of age) and without overt signs of head injury who underwent head CT or MRI had occult head injury; nearly all with occult head injury were <1 year of age. Intracranial injury is also associated with spinal trauma seen on skeletal survey [18].

69443

acrac_69443_6

Suspected Physical Abuse Child

Given these studies, clinicians should have a relatively low threshold for performing either CT (emergent setting and more sensitive for detection of nondisplaced fractures) or MRI of the head in children with suspected abuse. In summary, there is no strong evidence to recommend universal screening with neuroimaging. However, clinicians should have low threshold for performing head CT or MRI in young children with suspected child abuse. Variant 2: Suspected physical abuse. Child >24 months of age. Neurological or visceral injuries not clinically suspected. Initial imaging evaluation. X-ray area of interest Children >2 years of age are often able to verbalize the area(s) of injury or pain during clinical examination. Thus, initial imaging should focus on the areas of clinical concern. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs, but the study requires venipuncture and often requires sedation. CT head and MRI head Unenhanced CT of the head is the examination of choice for acute evaluation for intracranial injury in child abuse [33]. However, there is no strong evidence to recommend universal screening with neuroimaging in the absence of clinical suspicion for AHT. This is particularly true in older children where the neurological examination is typically more reliable, except for children with chronic disabilities. MRI is a good choice to image children for abusive head injury in the nonemergent setting. MRI is useful in the detection of small-volume extra-axial hemorrhage and for evolving parenchymal injury [36]. Diffusion-weighted imaging and susceptibility-weighted imaging increase the sensitivity for detection of parenchymal ischemia, diffuse axonal injury, and microhemorrhage. The addition of contrast-enhanced MRI sequences can be utilized in select cases to improve evaluation of extra-axial fluid collections.

Suspected Physical Abuse Child. Given these studies, clinicians should have a relatively low threshold for performing either CT (emergent setting and more sensitive for detection of nondisplaced fractures) or MRI of the head in children with suspected abuse. In summary, there is no strong evidence to recommend universal screening with neuroimaging. However, clinicians should have low threshold for performing head CT or MRI in young children with suspected child abuse. Variant 2: Suspected physical abuse. Child >24 months of age. Neurological or visceral injuries not clinically suspected. Initial imaging evaluation. X-ray area of interest Children >2 years of age are often able to verbalize the area(s) of injury or pain during clinical examination. Thus, initial imaging should focus on the areas of clinical concern. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs, but the study requires venipuncture and often requires sedation. CT head and MRI head Unenhanced CT of the head is the examination of choice for acute evaluation for intracranial injury in child abuse [33]. However, there is no strong evidence to recommend universal screening with neuroimaging in the absence of clinical suspicion for AHT. This is particularly true in older children where the neurological examination is typically more reliable, except for children with chronic disabilities. MRI is a good choice to image children for abusive head injury in the nonemergent setting. MRI is useful in the detection of small-volume extra-axial hemorrhage and for evolving parenchymal injury [36]. Diffusion-weighted imaging and susceptibility-weighted imaging increase the sensitivity for detection of parenchymal ischemia, diffuse axonal injury, and microhemorrhage. The addition of contrast-enhanced MRI sequences can be utilized in select cases to improve evaluation of extra-axial fluid collections.

69443

acrac_69443_7

Suspected Physical Abuse Child

Variant 3: Child with one or more of the following: neurologic signs or symptoms, apnea, complex skull fracture, other fractures, or injuries highly suspicious for child abuse. Initial imaging evaluation. X-ray skeletal survey The skeletal survey is the primary examination for detecting fractures [11]. Fractures occur in up to 55% of physically abused children [29]; 80% of abused children with fractures are <18 months of age [4]. Thus, skeletal survey is recommended in all children <2 years of age in whom there is suspicion of abuse [51,52]. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs. Skull fractures and fractures near the growth plates, however, may be difficult to appreciate [31,32]. In children with skull fractures or clinical signs and symptoms of intracranial injury, an immediate noncontrast CT scan of the head should be performed. Contrast administration for the head CT examination is not indicated. If the CT scan does not detect significant lesions that require rapid neurosurgical intervention and the clinical presentation warrants further assessment, a MRI scan of the head should be performed. MRI head Additional diagnostic information will be found on MRI over CT in about 25% of patients [36], and MRI can also contribute to prognosis. In a child with an abnormal CT, additional assessment with MRI should be considered to further assess the extent of post-traumatic injury. Care should be taken in trying to determine the age of subdural hematomas by CT or MRI [67,68]. Although hyperdense blood products can be considered acute, collections of low or intermediate density do not indicate necessarily chronic blood products, as lacerations of the arachnoid may result in subdural hygromas or hematohygromas in the early or late post-traumatic periods.

Suspected Physical Abuse Child. Variant 3: Child with one or more of the following: neurologic signs or symptoms, apnea, complex skull fracture, other fractures, or injuries highly suspicious for child abuse. Initial imaging evaluation. X-ray skeletal survey The skeletal survey is the primary examination for detecting fractures [11]. Fractures occur in up to 55% of physically abused children [29]; 80% of abused children with fractures are <18 months of age [4]. Thus, skeletal survey is recommended in all children <2 years of age in whom there is suspicion of abuse [51,52]. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs. Skull fractures and fractures near the growth plates, however, may be difficult to appreciate [31,32]. In children with skull fractures or clinical signs and symptoms of intracranial injury, an immediate noncontrast CT scan of the head should be performed. Contrast administration for the head CT examination is not indicated. If the CT scan does not detect significant lesions that require rapid neurosurgical intervention and the clinical presentation warrants further assessment, a MRI scan of the head should be performed. MRI head Additional diagnostic information will be found on MRI over CT in about 25% of patients [36], and MRI can also contribute to prognosis. In a child with an abnormal CT, additional assessment with MRI should be considered to further assess the extent of post-traumatic injury. Care should be taken in trying to determine the age of subdural hematomas by CT or MRI [67,68]. Although hyperdense blood products can be considered acute, collections of low or intermediate density do not indicate necessarily chronic blood products, as lacerations of the arachnoid may result in subdural hygromas or hematohygromas in the early or late post-traumatic periods.

69443

acrac_69443_8

Suspected Physical Abuse Child

MR venography utilizing unenhanced 2-dimensional time-of-flight technique can be used to assess patency of the dural venous sinuses and deep venous system. Neuroimaging should not be performed as a screening examination in all children but should be used for further evaluation of all abnormal initial examinations and in cases of clinical suspicion [36]. The clinician should have a relatively low threshold for performing either CT (emergent setting) or MRI of the head (nonemergent setting), especially in children under 1 year of age [60,61]. MRI cervical spine MRI of the cervical spine should be strongly considered at the time of MRI brain imaging, as unsuspected spinal injuries may be demonstrated in >36% of cases [44]. Cervical spine injury, particularly at the craniocervical junction, is highly associated with bilateral hypoxic-ischemic injury. Most cervical spine injury detected by MRI in abused infants is ligamentous. MRI complete spine MRI of the entire spine may show thoracolumbar SDH, most commonly from redistribution of blood products; however, it rarely results in cord compression or alters clinical management. An MRI of the total spine should be reserved for cases where the distinction between abusive and accidental trauma is not clear, since thoracolumbar SDH is more commonly seen with abusive trauma [43]. Variant 4: Child. Suspected physical abuse. Suspected thoracic or abdominopelvic injuries (eg, abdominal skin bruises, distension, tenderness, or elevated liver or pancreatic enzymes). Initial imaging evaluation. X-ray skeletal survey As most children with thoracic or abdominopelvic injury from child abuse have polytrauma [69], skeletal survey is recommended in all children 24 months of age or younger and should be considered in older children. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs.

Suspected Physical Abuse Child. MR venography utilizing unenhanced 2-dimensional time-of-flight technique can be used to assess patency of the dural venous sinuses and deep venous system. Neuroimaging should not be performed as a screening examination in all children but should be used for further evaluation of all abnormal initial examinations and in cases of clinical suspicion [36]. The clinician should have a relatively low threshold for performing either CT (emergent setting) or MRI of the head (nonemergent setting), especially in children under 1 year of age [60,61]. MRI cervical spine MRI of the cervical spine should be strongly considered at the time of MRI brain imaging, as unsuspected spinal injuries may be demonstrated in >36% of cases [44]. Cervical spine injury, particularly at the craniocervical junction, is highly associated with bilateral hypoxic-ischemic injury. Most cervical spine injury detected by MRI in abused infants is ligamentous. MRI complete spine MRI of the entire spine may show thoracolumbar SDH, most commonly from redistribution of blood products; however, it rarely results in cord compression or alters clinical management. An MRI of the total spine should be reserved for cases where the distinction between abusive and accidental trauma is not clear, since thoracolumbar SDH is more commonly seen with abusive trauma [43]. Variant 4: Child. Suspected physical abuse. Suspected thoracic or abdominopelvic injuries (eg, abdominal skin bruises, distension, tenderness, or elevated liver or pancreatic enzymes). Initial imaging evaluation. X-ray skeletal survey As most children with thoracic or abdominopelvic injury from child abuse have polytrauma [69], skeletal survey is recommended in all children 24 months of age or younger and should be considered in older children. Tc-99m bone scan whole body Bone scintigraphy is a complementary/adjunctive examination for detecting bone injuries. It may aid by detecting bony injury that is occult, equivocal, or subtle on plain radiographs.

69443

acrac_69443_9

Suspected Physical Abuse Child

CT head and MRI head CT or MRI of the head should also be performed in children with neurologic symptoms or risk factors for intracranial injuries (see variant 3). CT of the abdomen and pelvis Nonskeletal injuries to the chest, abdomen, and pelvis can occur as the result of child abuse. Child abuse should be considered in any child with thoracoabdominal injuries that are not consistent with the provided history. Up to 10% of abused children have intra-abdominal injury [49]; 15% of children aged 0 to 4 years hospitalized for abdominal injury are victims of child abuse [70,71]. Victims of nonaccidental abdominal trauma tend to be younger and have a more delayed presentation than those who experience accidental trauma [72]. Clinical findings of abdominal pain, abdominal distension, vomiting, abdominal wall bruising, and hypoactive or absent bowel sounds may suggest intra-abdominal injury [73-75]. Abnormal liver transaminases and pancreatic enzymes may be seen with occult abdominal trauma [74,75]. One series suggested that nearly half of abused children with abdominal injury require surgical intervention [76]. In addition, independent of concomitant injury, blunt trauma due to child abuse is associated with a 6-fold increase in odds of death compared to children whose injuries resulted from accidental trauma [70]. Nonskeletal abdominopelvic injuries include pancreatitis, pancreatic pseudocysts, and lacerations and contusions of the liver, adrenal gland, spleen, kidneys, and bowel (especially duodenum) [77,78]. Bowel injuries and pancreatic injuries are seen disproportionately more often in child abuse compared to accidental trauma [49]. Contrast-enhanced CT of the abdomen is indicated in acute evaluation of the child with suspected abdominopelvic injuries. The use of ultrasound in the acute setting is limited, as both focused abdominal scan in trauma and standard abdominopelvic ultrasound are less sensitive than CT in detection of hemoperitoneum and solid-organ injuries [79,80].

Suspected Physical Abuse Child. CT head and MRI head CT or MRI of the head should also be performed in children with neurologic symptoms or risk factors for intracranial injuries (see variant 3). CT of the abdomen and pelvis Nonskeletal injuries to the chest, abdomen, and pelvis can occur as the result of child abuse. Child abuse should be considered in any child with thoracoabdominal injuries that are not consistent with the provided history. Up to 10% of abused children have intra-abdominal injury [49]; 15% of children aged 0 to 4 years hospitalized for abdominal injury are victims of child abuse [70,71]. Victims of nonaccidental abdominal trauma tend to be younger and have a more delayed presentation than those who experience accidental trauma [72]. Clinical findings of abdominal pain, abdominal distension, vomiting, abdominal wall bruising, and hypoactive or absent bowel sounds may suggest intra-abdominal injury [73-75]. Abnormal liver transaminases and pancreatic enzymes may be seen with occult abdominal trauma [74,75]. One series suggested that nearly half of abused children with abdominal injury require surgical intervention [76]. In addition, independent of concomitant injury, blunt trauma due to child abuse is associated with a 6-fold increase in odds of death compared to children whose injuries resulted from accidental trauma [70]. Nonskeletal abdominopelvic injuries include pancreatitis, pancreatic pseudocysts, and lacerations and contusions of the liver, adrenal gland, spleen, kidneys, and bowel (especially duodenum) [77,78]. Bowel injuries and pancreatic injuries are seen disproportionately more often in child abuse compared to accidental trauma [49]. Contrast-enhanced CT of the abdomen is indicated in acute evaluation of the child with suspected abdominopelvic injuries. The use of ultrasound in the acute setting is limited, as both focused abdominal scan in trauma and standard abdominopelvic ultrasound are less sensitive than CT in detection of hemoperitoneum and solid-organ injuries [79,80].

69443

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Suspected Physical Abuse Child

Noncontrast CT of the abdomen is not adequately sensitive in detection of intrathoracic or intra-abdominal trauma. Routine CT scan screening for abdominal or chest injury is not recommended [72]. CT of the chest Injuries to the chest (other than the ribs) are uncommon and include hemopericardium, cardiac contusions and lacerations, pleural effusion, and lung contusions [23,64,77,81]. Contrast-enhanced CT of the chest is indicated in acute evaluation of the child with these types of suspected nonskeletal intrathoracic injury; noncontrast CT of the chest is not adequately sensitive. Routine CT scan screening for chest injury is not recommended [72]. In children <24 months of age, a repeat skeletal survey performed approximately 2 weeks after the initial examination can detect fractures not seen on initial skeletal survey, can clarify equivocal findings, and can provide information on the age of child abuse fractures [22,26,83]. Nine to 12% of infants have healing fractures on follow-up survey after a negative initial survey [82,84], and up to one-third of follow-up surveys yield new information [84]. Half to three-fourths of these newly detected fractures are rib fractures [26,82,84]; classic metaphyseal lesions are the second most common [83]. As such, many authors have suggested a more limited follow-up skeletal survey, as described above. However, it is not possible to exactly date fractures by radiography [27]. Tc-99m bone scan whole body In selected cases, when it is not possible to wait 2 weeks for a follow-up skeletal survey radiograph, a bone scan can be considered. Bone scan is sensitive in detecting radiographically occult fractures. It is particularly useful in detection of fractures of the ribs, scapula, spine, and pelvis [30]. It is not sensitive, however, in the detection of skull fractures [29]. Metaphyseal injury may be difficult to see because of the adjacent normal metabolically active physis. Radiation exposure is higher than a skeletal survey [29].

Suspected Physical Abuse Child. Noncontrast CT of the abdomen is not adequately sensitive in detection of intrathoracic or intra-abdominal trauma. Routine CT scan screening for abdominal or chest injury is not recommended [72]. CT of the chest Injuries to the chest (other than the ribs) are uncommon and include hemopericardium, cardiac contusions and lacerations, pleural effusion, and lung contusions [23,64,77,81]. Contrast-enhanced CT of the chest is indicated in acute evaluation of the child with these types of suspected nonskeletal intrathoracic injury; noncontrast CT of the chest is not adequately sensitive. Routine CT scan screening for chest injury is not recommended [72]. In children <24 months of age, a repeat skeletal survey performed approximately 2 weeks after the initial examination can detect fractures not seen on initial skeletal survey, can clarify equivocal findings, and can provide information on the age of child abuse fractures [22,26,83]. Nine to 12% of infants have healing fractures on follow-up survey after a negative initial survey [82,84], and up to one-third of follow-up surveys yield new information [84]. Half to three-fourths of these newly detected fractures are rib fractures [26,82,84]; classic metaphyseal lesions are the second most common [83]. As such, many authors have suggested a more limited follow-up skeletal survey, as described above. However, it is not possible to exactly date fractures by radiography [27]. Tc-99m bone scan whole body In selected cases, when it is not possible to wait 2 weeks for a follow-up skeletal survey radiograph, a bone scan can be considered. Bone scan is sensitive in detecting radiographically occult fractures. It is particularly useful in detection of fractures of the ribs, scapula, spine, and pelvis [30]. It is not sensitive, however, in the detection of skull fractures [29]. Metaphyseal injury may be difficult to see because of the adjacent normal metabolically active physis. Radiation exposure is higher than a skeletal survey [29].

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acrac_69443_11

Suspected Physical Abuse Child

If used in follow-up, radiographs of areas of abnormal uptake should also be performed. CT chest Low-dose noncontrast CT of the chest also offers a time advantage over repeat skeletal survey. It is useful in the detection of rib, scapula, and thoracic spine fractures not seen on skeletal survey [47]. Anterior and posterior rib fractures are detected more often by CT than by skeletal survey [46]. Fractures may also be dated as acute, subacute, or chronic [46,85]. It would not replace contrast-enhanced chest CT in initial evaluation of nonskeletal thoracic injuries, such as hemopericardium, cardiac contusions and lacerations, pleural effusion, and lung contusions [23,64,77,81]. CT head and MRI head Follow-up neuroimaging is usually not indicated in the setting of a negative skeletal survey and absence of clinical suspicion of AHT. If there is suspicion for injury after the initial evaluation, neuroimaging should be considered. Noncontrast CT is useful in the evaluation of healing skull fractures, whereas MRI is the method of choice to evaluate the intracranial compartment. Summary of Recommendations The appropriate imaging of pediatric patients being evaluated for suspected physical abuse depends upon the age of the child, the presence of neurological signs and symptoms, and evidence of visceral thoracic or abdominopelvic injuries. A skeletal survey is indicated in the initial imaging evaluation of a child 24 months of age or younger. In older children, it is usually appropriate to target imaging to the area(s) of suspected injury. Skeletal survey and CT head without contrast are indicated in the emergent/initial imaging evaluation of a child with neurologic signs and symptoms, complex skull fracture, apnea, multiple fractures, spine trauma, or facial injury. These examinations are not indicated for general screening. MRI head may provide additional diagnostic information to head CT in about 25% of children.

Suspected Physical Abuse Child. If used in follow-up, radiographs of areas of abnormal uptake should also be performed. CT chest Low-dose noncontrast CT of the chest also offers a time advantage over repeat skeletal survey. It is useful in the detection of rib, scapula, and thoracic spine fractures not seen on skeletal survey [47]. Anterior and posterior rib fractures are detected more often by CT than by skeletal survey [46]. Fractures may also be dated as acute, subacute, or chronic [46,85]. It would not replace contrast-enhanced chest CT in initial evaluation of nonskeletal thoracic injuries, such as hemopericardium, cardiac contusions and lacerations, pleural effusion, and lung contusions [23,64,77,81]. CT head and MRI head Follow-up neuroimaging is usually not indicated in the setting of a negative skeletal survey and absence of clinical suspicion of AHT. If there is suspicion for injury after the initial evaluation, neuroimaging should be considered. Noncontrast CT is useful in the evaluation of healing skull fractures, whereas MRI is the method of choice to evaluate the intracranial compartment. Summary of Recommendations The appropriate imaging of pediatric patients being evaluated for suspected physical abuse depends upon the age of the child, the presence of neurological signs and symptoms, and evidence of visceral thoracic or abdominopelvic injuries. A skeletal survey is indicated in the initial imaging evaluation of a child 24 months of age or younger. In older children, it is usually appropriate to target imaging to the area(s) of suspected injury. Skeletal survey and CT head without contrast are indicated in the emergent/initial imaging evaluation of a child with neurologic signs and symptoms, complex skull fracture, apnea, multiple fractures, spine trauma, or facial injury. These examinations are not indicated for general screening. MRI head may provide additional diagnostic information to head CT in about 25% of children.

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acrac_3094199_0

Tinnitus

Introduction/Background Tinnitus is a symptom defined by the perception of sound in the absence of external stimuli. It affects more than 50 million Americans, equally among men and women, and is most commonly noted in patients between 40 and 70 years of age [1]. Tinnitus may range from innocuous to devastating, with significant negative impacts on psychosocial well-being and quality of life. In a survey conducted in 2008, approximately 10% of the United States adult population experienced endorsed at least 1 episode of tinnitus lasting more than 5 minutes in the preceding year [2]. It is important to know the otoscopy examination findings in patients with PT because it guides the imaging algorithm. In the setting of PT, the possibility of a vascular retrotympanic lesion leads to a different set of differential diagnostic considerations compared to the absence thereof and therefore influences the decision for which imaging studies to pursue and in what order. However, the detection of retrotympanic lesions can be difficult without appropriate equipment. The American Academy of Otolaryngology and Head and Neck Surgery Foundation (AAO-HNS) guidelines recommend targeted history and clinical examination as the initial evaluation and determination as to whether the tinnitus is bothersome or not, before any imaging. The guidelines also recommend a prompt and comprehensive audiological examination in patients with hearing problems or with unilateral persistent tinnitus. The guidelines make a strong recommendation against any imaging studies of the head and neck for the subset of patients in whom tinnitus does not localize to 1 ear, is nonpulsatile, and is not associated with focal neurological abnormalities or an asymmetric hearing loss. The guidelines also suggest that some patients with severe anxiety, depression, or psychological disturbances may need prompt identification and intervention [6,7]. aMetroHealth Medical Center, Cleveland, Ohio.

Tinnitus. Introduction/Background Tinnitus is a symptom defined by the perception of sound in the absence of external stimuli. It affects more than 50 million Americans, equally among men and women, and is most commonly noted in patients between 40 and 70 years of age [1]. Tinnitus may range from innocuous to devastating, with significant negative impacts on psychosocial well-being and quality of life. In a survey conducted in 2008, approximately 10% of the United States adult population experienced endorsed at least 1 episode of tinnitus lasting more than 5 minutes in the preceding year [2]. It is important to know the otoscopy examination findings in patients with PT because it guides the imaging algorithm. In the setting of PT, the possibility of a vascular retrotympanic lesion leads to a different set of differential diagnostic considerations compared to the absence thereof and therefore influences the decision for which imaging studies to pursue and in what order. However, the detection of retrotympanic lesions can be difficult without appropriate equipment. The American Academy of Otolaryngology and Head and Neck Surgery Foundation (AAO-HNS) guidelines recommend targeted history and clinical examination as the initial evaluation and determination as to whether the tinnitus is bothersome or not, before any imaging. The guidelines also recommend a prompt and comprehensive audiological examination in patients with hearing problems or with unilateral persistent tinnitus. The guidelines make a strong recommendation against any imaging studies of the head and neck for the subset of patients in whom tinnitus does not localize to 1 ear, is nonpulsatile, and is not associated with focal neurological abnormalities or an asymmetric hearing loss. The guidelines also suggest that some patients with severe anxiety, depression, or psychological disturbances may need prompt identification and intervention [6,7]. aMetroHealth Medical Center, Cleveland, Ohio.

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Tinnitus

bPanel Chair, University of Iowa Hospitals and Clinics, Iowa City, Iowa. cPanel Vice-Chair, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. dThe Ohio State University Wexner Medical Center, Columbus, Ohio; American Academy of Otolaryngology-Head and Neck Surgery. eFroedtert Memorial Lutheran Hospital Medical College of Wisconsin, Milwaukee, Wisconsin. fHouston Methodist Hospital, Houston, Texas. gHouston Methodist Hospital, Houston, Texas. hThe University of Texas MD Anderson Cancer Center, Houston, Texas. iNew York University Langone Medical Center, New York, New York. jMayo Clinic, Rochester, Minnesota; Commission on Nuclear Medicine and Molecular Imaging. kSentara Norfolk General Hospital/Eastern Virginia Medical School, Norfolk, Virginia; American College of Emergency Physicians. lJohns Hopkins University School of Medicine, Baltimore, Maryland; American Geriatrics Society. mMayo Clinic Arizona, Phoenix, Arizona. nColumbia University Medical Center, New York, New York; American Academy of Neurology. oEvansville Primary Care, Evansville, Indiana; American Academy of Family Physicians. pGeorge Washington University Hospital, Washington, District of Columbia. qUniversity of Colorado Denver, Denver, Colorado. rSpecialty Chair, Montefiore Medical Center, Bronx, New York. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Special Imaging Considerations CT angiography (CTA) can be performed to include a mixed arterial and venous phase through the head and neck in selected clinical scenarios.

Tinnitus. bPanel Chair, University of Iowa Hospitals and Clinics, Iowa City, Iowa. cPanel Vice-Chair, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. dThe Ohio State University Wexner Medical Center, Columbus, Ohio; American Academy of Otolaryngology-Head and Neck Surgery. eFroedtert Memorial Lutheran Hospital Medical College of Wisconsin, Milwaukee, Wisconsin. fHouston Methodist Hospital, Houston, Texas. gHouston Methodist Hospital, Houston, Texas. hThe University of Texas MD Anderson Cancer Center, Houston, Texas. iNew York University Langone Medical Center, New York, New York. jMayo Clinic, Rochester, Minnesota; Commission on Nuclear Medicine and Molecular Imaging. kSentara Norfolk General Hospital/Eastern Virginia Medical School, Norfolk, Virginia; American College of Emergency Physicians. lJohns Hopkins University School of Medicine, Baltimore, Maryland; American Geriatrics Society. mMayo Clinic Arizona, Phoenix, Arizona. nColumbia University Medical Center, New York, New York; American Academy of Neurology. oEvansville Primary Care, Evansville, Indiana; American Academy of Family Physicians. pGeorge Washington University Hospital, Washington, District of Columbia. qUniversity of Colorado Denver, Denver, Colorado. rSpecialty Chair, Montefiore Medical Center, Bronx, New York. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Special Imaging Considerations CT angiography (CTA) can be performed to include a mixed arterial and venous phase through the head and neck in selected clinical scenarios.

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acrac_3094199_2

Tinnitus

In these cases, imaging can be performed after peak arterial timing and can be obtained approximately 20 to 25 seconds after injection of intravenous (IV) contrast material. This allows for a single test with lower total radiation dose when compared to separate CTA and CT venography (CTV) examinations. Overlapping of vessels is not problematic, and it shows not only both arterial and venous anatomy and pathology adequately in this balanced phase but also the bony details of the temporal bone when reconstructed in thin bone window settings [1,11,12]. MR brain, when performed for temporal bone/skull base evaluation of tinnitus, is usually performed using specialized internal auditory canal (IAC) protocols, which include thin-section, heavily T2-weighted sequences to evaluate for vascular loops and small vestibular schwannomas. Volumetric postcontrast T1-weighted images are also increasingly becoming a part of this protocol, which has the added benefit of assessment of the transverse and sigmoid sinuses. Functional MRI in patients with tinnitus is still a research tool and is not used in routine applications [13,14]. Venous arterial spin-labeling technique has a high sensitivity and specificity for the presence of a dural arteriovenous fistula (dAVF), and the addition of spin-labeling increases confidence in the diagnosis of this entity on MRI [15]. Time-resolved gadolinium-enhanced MR angiography (MRA) is a technique which combines many factors like T1 shortening effect of gadolinium, digital subtraction technique, dynamic imaging, and parallel imaging to provide high temporal resolution MRA images. Use of intelligent k-space sampling technique can further improve the spatial and temporal resolution. The rapid acquisition of multiple 3-D volumes with high temporal and spatial resolution renders excellent depiction of the vessels to detect dAVFs [16-18]. OR Discussion of Procedures by Variant Variant 1: Pulsatile tinnitus, unilateral or bilateral; no retrotympanic lesion on otoscopy. Initial imaging.

Tinnitus. In these cases, imaging can be performed after peak arterial timing and can be obtained approximately 20 to 25 seconds after injection of intravenous (IV) contrast material. This allows for a single test with lower total radiation dose when compared to separate CTA and CT venography (CTV) examinations. Overlapping of vessels is not problematic, and it shows not only both arterial and venous anatomy and pathology adequately in this balanced phase but also the bony details of the temporal bone when reconstructed in thin bone window settings [1,11,12]. MR brain, when performed for temporal bone/skull base evaluation of tinnitus, is usually performed using specialized internal auditory canal (IAC) protocols, which include thin-section, heavily T2-weighted sequences to evaluate for vascular loops and small vestibular schwannomas. Volumetric postcontrast T1-weighted images are also increasingly becoming a part of this protocol, which has the added benefit of assessment of the transverse and sigmoid sinuses. Functional MRI in patients with tinnitus is still a research tool and is not used in routine applications [13,14]. Venous arterial spin-labeling technique has a high sensitivity and specificity for the presence of a dural arteriovenous fistula (dAVF), and the addition of spin-labeling increases confidence in the diagnosis of this entity on MRI [15]. Time-resolved gadolinium-enhanced MR angiography (MRA) is a technique which combines many factors like T1 shortening effect of gadolinium, digital subtraction technique, dynamic imaging, and parallel imaging to provide high temporal resolution MRA images. Use of intelligent k-space sampling technique can further improve the spatial and temporal resolution. The rapid acquisition of multiple 3-D volumes with high temporal and spatial resolution renders excellent depiction of the vessels to detect dAVFs [16-18]. OR Discussion of Procedures by Variant Variant 1: Pulsatile tinnitus, unilateral or bilateral; no retrotympanic lesion on otoscopy. Initial imaging.

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acrac_3094199_3

Tinnitus

PT has many causes, and no single imaging study is appropriate for all patients. A diagnostic algorithm based on a detailed history and clinical evaluation should progress from less invasive to more invasive imaging studies. The history and clinical assessment have implications on the choice of imaging modality [12,19]. For example, an otoscopic examination is extremely useful to help guide optimal imaging evaluation of PT. Tinnitus Sigmoid sinus wall dehiscence and sigmoid sinus diverticulum are collectively called sigmoid sinus wall abnormalities (SSWA) and are increasingly recognized causes of PT [19,25-27]. Structural and anatomic causes of PT can be found in up to 44% to 91% of patients; however, in some studies, many patients remained idiopathic even after extensive workup [28,29]. The history and physical examination may also suggest PT due to systemic causes such as pregnancy-related hemodynamic changes, anemia, thyrotoxicosis, or due to mechanical causes like palatal or tympanic myoclonus, Eustachian tube contractions, or temporomandibular joint problems [30-34]. Arteriography Cervicocerebral Arteriography is an invasive test, which can diagnose many conditions causing PT, and is used when noninvasive tests like CTA and MRA are inconclusive and there is persistent clinical suspicion for a vascular lesion. It is particularly useful for detecting dAVFs and other lesions with arteriovenous shunts such as AVM and carotid cavernous sinus fistulas [35]. These lesions may cause PT, and arteriography has a higher sensitivity and specificity than MRA or CTA, which are used for screening. Therefore, arteriography is still useful if CTA/MRA is negative but dAVF remains suspected to be the cause of PT [23,29]. It is also useful for preoperative planning and embolization for paragangliomas [36]. A study found an incidence of 24% for arteriovenous shunts in patients who were referred for digital subtraction angiography (DSA) for evaluation of PT.

Tinnitus. PT has many causes, and no single imaging study is appropriate for all patients. A diagnostic algorithm based on a detailed history and clinical evaluation should progress from less invasive to more invasive imaging studies. The history and clinical assessment have implications on the choice of imaging modality [12,19]. For example, an otoscopic examination is extremely useful to help guide optimal imaging evaluation of PT. Tinnitus Sigmoid sinus wall dehiscence and sigmoid sinus diverticulum are collectively called sigmoid sinus wall abnormalities (SSWA) and are increasingly recognized causes of PT [19,25-27]. Structural and anatomic causes of PT can be found in up to 44% to 91% of patients; however, in some studies, many patients remained idiopathic even after extensive workup [28,29]. The history and physical examination may also suggest PT due to systemic causes such as pregnancy-related hemodynamic changes, anemia, thyrotoxicosis, or due to mechanical causes like palatal or tympanic myoclonus, Eustachian tube contractions, or temporomandibular joint problems [30-34]. Arteriography Cervicocerebral Arteriography is an invasive test, which can diagnose many conditions causing PT, and is used when noninvasive tests like CTA and MRA are inconclusive and there is persistent clinical suspicion for a vascular lesion. It is particularly useful for detecting dAVFs and other lesions with arteriovenous shunts such as AVM and carotid cavernous sinus fistulas [35]. These lesions may cause PT, and arteriography has a higher sensitivity and specificity than MRA or CTA, which are used for screening. Therefore, arteriography is still useful if CTA/MRA is negative but dAVF remains suspected to be the cause of PT [23,29]. It is also useful for preoperative planning and embolization for paragangliomas [36]. A study found an incidence of 24% for arteriovenous shunts in patients who were referred for digital subtraction angiography (DSA) for evaluation of PT.

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acrac_3094199_4

Tinnitus

Other retrospective studies showed a prevalence of 2% to 27% for arteriovenous shunts in patients with PT undergoing DSA [35]. Cervical artery dissection (carotid or vertebral) can also cause PT in 8% to 10% of patients with PT and can be diagnosed by CTA, MRA, or catheter arteriography. Catheter arteriography is rarely required for this indication; however, because of the excellent accuracy of CTA and MRA [37,38]. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Temporal Bone With IV Contrast There is no relevant literature to support the use of CT temporal bone with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. IV contrast is not needed in the assessment of semicircular canal dehiscence, enlarged vestibular aqueduct, SSWA, jugular bulb dehiscence, or glomus jugulare paraganglioma. This may detect transverse sinus stenosis and some cases of dAVFs but cannot assess the neck vessels. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Temporal Bone Without IV Contrast CT temporal bone without IV contrast does not show the arterial abnormalities in the neck, or intracranial vascular abnormalities such as dAVF, AVM, and transverse sinus stenosis, which are potential causes in this setting.

Tinnitus. Other retrospective studies showed a prevalence of 2% to 27% for arteriovenous shunts in patients with PT undergoing DSA [35]. Cervical artery dissection (carotid or vertebral) can also cause PT in 8% to 10% of patients with PT and can be diagnosed by CTA, MRA, or catheter arteriography. Catheter arteriography is rarely required for this indication; however, because of the excellent accuracy of CTA and MRA [37,38]. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Temporal Bone With IV Contrast There is no relevant literature to support the use of CT temporal bone with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. IV contrast is not needed in the assessment of semicircular canal dehiscence, enlarged vestibular aqueduct, SSWA, jugular bulb dehiscence, or glomus jugulare paraganglioma. This may detect transverse sinus stenosis and some cases of dAVFs but cannot assess the neck vessels. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. CT Temporal Bone Without IV Contrast CT temporal bone without IV contrast does not show the arterial abnormalities in the neck, or intracranial vascular abnormalities such as dAVF, AVM, and transverse sinus stenosis, which are potential causes in this setting.

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acrac_3094199_5

Tinnitus

High- resolution CT (HRCT) of the temporal bone can detect some other conditions that cause PT but do not always present as a vascular retrotympanic mass, such as otospongiosis, Paget disease, sigmoid sinus diverticulum and sigmoid sinus dehiscence, high-riding jugular bulb, and SSCD [39]. SSCD is a known cause of PT and other symptoms of peripheral vestibulopathy and is readily diagnosed on CT temporal bone [40,41]. SSWAs are known causes of PT and may be the most common identifiable causes in this group [25]. They are much more frequently seen on CT temporal bone in patients with PT compared with the general population and are a common and treatable cause of PT [19,26,27,42]. It can be readily diagnosed with either CT temporal bone or CTA/CTV of the head [19]. One study found that SSWA was seen in all patients with venous PT in addition to other venous abnormalities [43]. IV contrast is not necessary. CT temporal bone has a smaller field-of-view and a higher resolution to evaluate the temporal bone compared with CTA. Tinnitus Labyrinthine sequestrum is a very rare infective condition in which there is destruction of the inner ear structures and can cause tinnitus in addition to other symptoms. On CT, one may see erosion of the bony labyrinth. On MRI, there may be abnormal enhancement of the labyrinthine contents on the postcontrast images [44]. Slight modification from usual CTA bolus timing can allow for a balanced phase examination facilitating detection of both arterial and venous etiologies of PT in the head and neck. Therefore, it is the imaging modality of choice in patients with PT without a suspected retrotympanic lesion because it can show both arterial and venous pathologies in the head, skull base, and neck, in addition to the bony details of the temporal bone. Temporal bone anatomy is also well seen on thin bone window reconstructions, which cannot be assessed on MRA/MRI.

Tinnitus. High- resolution CT (HRCT) of the temporal bone can detect some other conditions that cause PT but do not always present as a vascular retrotympanic mass, such as otospongiosis, Paget disease, sigmoid sinus diverticulum and sigmoid sinus dehiscence, high-riding jugular bulb, and SSCD [39]. SSCD is a known cause of PT and other symptoms of peripheral vestibulopathy and is readily diagnosed on CT temporal bone [40,41]. SSWAs are known causes of PT and may be the most common identifiable causes in this group [25]. They are much more frequently seen on CT temporal bone in patients with PT compared with the general population and are a common and treatable cause of PT [19,26,27,42]. It can be readily diagnosed with either CT temporal bone or CTA/CTV of the head [19]. One study found that SSWA was seen in all patients with venous PT in addition to other venous abnormalities [43]. IV contrast is not necessary. CT temporal bone has a smaller field-of-view and a higher resolution to evaluate the temporal bone compared with CTA. Tinnitus Labyrinthine sequestrum is a very rare infective condition in which there is destruction of the inner ear structures and can cause tinnitus in addition to other symptoms. On CT, one may see erosion of the bony labyrinth. On MRI, there may be abnormal enhancement of the labyrinthine contents on the postcontrast images [44]. Slight modification from usual CTA bolus timing can allow for a balanced phase examination facilitating detection of both arterial and venous etiologies of PT in the head and neck. Therefore, it is the imaging modality of choice in patients with PT without a suspected retrotympanic lesion because it can show both arterial and venous pathologies in the head, skull base, and neck, in addition to the bony details of the temporal bone. Temporal bone anatomy is also well seen on thin bone window reconstructions, which cannot be assessed on MRA/MRI.

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acrac_3094199_6

Tinnitus

Bony reconstructions from CTA thus can show SSWA such as diverticulum and wall dehiscence due to bony contour abnormalities [27]. However, 1 study reported a cause of PT being found only in 68% to 72% of patients with PT despite an extensive workup with CTA, MRI, and ultrasound (US) [12]. Fibromuscular dysplasia of the carotids, atherosclerotic disease, vascular dissection, and carotid aneurysms in the neck can also cause PT, which can be accurately diagnosed by CTA head and neck [1,23,28,46,49]. Slight modification from usual CTA bolus timing can allow for a balanced phase examination facilitating detection of both arterial and venous etiologies of PT in the head and neck. Therefore, it is the imaging modality of choice in patients with PT without a suspected retrotympanic lesion because it can show both arterial and venous pathologies in the head, skull base, and neck, in addition to the bony details of the temporal bone. Temporal bone anatomy is also well seen on thin bone window reconstructions, which cannot be assessed on MRA/MRI. Bony reconstructions from CTA thus can show SSWA such as diverticulum and wall dehiscence due to bony contour abnormalities [27]. However, 1 study reported a cause of PT being found only in 68% to 72% of patients with PT despite an extensive workup with CTA, MRI, and US [12]. CTA head does not cover the neck and therefore will not be able to detect the vascular abnormalities in the neck that can cause PT. CTV Head With IV Contrast CTV can readily show various venous causes of PT such as transverse sinus stenosis and SSWA such as dehiscence and diverticulum. Transverse sinus stenosis, sigmoid sinus diverticulum, and sigmoid sinus dehiscence have been proposed as potential causes for PT [50]. Thin-section bone window reconstructions from the CTV are used to detect wall dehiscence, whereas diverticulum is seen on both CTV and bone window reconstruction images.

Tinnitus. Bony reconstructions from CTA thus can show SSWA such as diverticulum and wall dehiscence due to bony contour abnormalities [27]. However, 1 study reported a cause of PT being found only in 68% to 72% of patients with PT despite an extensive workup with CTA, MRI, and ultrasound (US) [12]. Fibromuscular dysplasia of the carotids, atherosclerotic disease, vascular dissection, and carotid aneurysms in the neck can also cause PT, which can be accurately diagnosed by CTA head and neck [1,23,28,46,49]. Slight modification from usual CTA bolus timing can allow for a balanced phase examination facilitating detection of both arterial and venous etiologies of PT in the head and neck. Therefore, it is the imaging modality of choice in patients with PT without a suspected retrotympanic lesion because it can show both arterial and venous pathologies in the head, skull base, and neck, in addition to the bony details of the temporal bone. Temporal bone anatomy is also well seen on thin bone window reconstructions, which cannot be assessed on MRA/MRI. Bony reconstructions from CTA thus can show SSWA such as diverticulum and wall dehiscence due to bony contour abnormalities [27]. However, 1 study reported a cause of PT being found only in 68% to 72% of patients with PT despite an extensive workup with CTA, MRI, and US [12]. CTA head does not cover the neck and therefore will not be able to detect the vascular abnormalities in the neck that can cause PT. CTV Head With IV Contrast CTV can readily show various venous causes of PT such as transverse sinus stenosis and SSWA such as dehiscence and diverticulum. Transverse sinus stenosis, sigmoid sinus diverticulum, and sigmoid sinus dehiscence have been proposed as potential causes for PT [50]. Thin-section bone window reconstructions from the CTV are used to detect wall dehiscence, whereas diverticulum is seen on both CTV and bone window reconstruction images.

3094199

acrac_3094199_7

Tinnitus

The SSWAs are seen because of bony contour abnormalities, and contrast offers confirmatory value in diverticulum but is not imperative. SSWAs are much more frequently seen on CT temporal bones among patients with PT compared to the general population [26]. SSWAs are a known cause of vascular PT, and 4% to 32% of PT patients may have it, and they can be successfully treated by wall reconstruction or endovascular stenting [51-55]. Some studies have shown that the degree of transverse sinus stenosis seen on CTV correlates well with transstenotic pressure gradient measured on catheter manometry [26,43,56]. Transverse sinus stenosis could be a cause or result Tinnitus of IIH or SSWA [26,56]. Approximately 60% of the patients of IIH experience tinnitus. Stent placement in transverse sinus stenosis for disabling cases of PT can be curative [57]. Abrupt change in the luminal caliber of the transverse sinus is proposed as a possible etiology for PT and can be seen on CTV of the head. Unilateral dominant size of the venous system is a normal variant in the general population but is equivocal as a causal factor for PT [45]. Venous causes of PT are more frequent than arterial causes [11]. CTV cannot detect arterial abnormalities, whereas a CTA/CTV can detect both arterial and venous abnormalities. MRA Head With IV Contrast MRA head with IV contrast can diagnose dAVF, AVM, and larger glomus jugulare tumors, which can cause PT. A study on 54 patients with PT found excellent accuracy of combined MRA and MRI head without and with IV contrast to detect various pathologies causing PT such as dAVF, AVM, and paragangliomas [58]. IV contrast improves the sensitivity to detect dAVF, AVM, and vascular tumors like glomus jugulare. Time-resolved gadolinium-enhanced MRA is a useful technique in showing vessels with high temporal and spatial resolution to detect dAVFs. It is a reliable technique in the screening and surveillance of DAVF [16,18].

Tinnitus. The SSWAs are seen because of bony contour abnormalities, and contrast offers confirmatory value in diverticulum but is not imperative. SSWAs are much more frequently seen on CT temporal bones among patients with PT compared to the general population [26]. SSWAs are a known cause of vascular PT, and 4% to 32% of PT patients may have it, and they can be successfully treated by wall reconstruction or endovascular stenting [51-55]. Some studies have shown that the degree of transverse sinus stenosis seen on CTV correlates well with transstenotic pressure gradient measured on catheter manometry [26,43,56]. Transverse sinus stenosis could be a cause or result Tinnitus of IIH or SSWA [26,56]. Approximately 60% of the patients of IIH experience tinnitus. Stent placement in transverse sinus stenosis for disabling cases of PT can be curative [57]. Abrupt change in the luminal caliber of the transverse sinus is proposed as a possible etiology for PT and can be seen on CTV of the head. Unilateral dominant size of the venous system is a normal variant in the general population but is equivocal as a causal factor for PT [45]. Venous causes of PT are more frequent than arterial causes [11]. CTV cannot detect arterial abnormalities, whereas a CTA/CTV can detect both arterial and venous abnormalities. MRA Head With IV Contrast MRA head with IV contrast can diagnose dAVF, AVM, and larger glomus jugulare tumors, which can cause PT. A study on 54 patients with PT found excellent accuracy of combined MRA and MRI head without and with IV contrast to detect various pathologies causing PT such as dAVF, AVM, and paragangliomas [58]. IV contrast improves the sensitivity to detect dAVF, AVM, and vascular tumors like glomus jugulare. Time-resolved gadolinium-enhanced MRA is a useful technique in showing vessels with high temporal and spatial resolution to detect dAVFs. It is a reliable technique in the screening and surveillance of DAVF [16,18].

3094199

acrac_3094199_8

Tinnitus

Catheter angiography has better sensitivity and may still be considered if MR studies are negative and dAVF is still suspected [1,23,29]. MRA head cannot identify bony lesions like jugular fossa dehiscence, SSWA, SSCD, intracranial mass lesions, and venous causes of PT. It is usually combined with MRI head with and without contrast for a better evaluation of intracranial pathologies which can cause PT. MRA Head Without and With IV Contrast MRA head without and with IV contrast may be used to detect dAVF, AVM, larger glomus jugulare tumors, carotid dissection, and carotid cavernous fistula for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. Catheter angiography has better sensitivity and may still be considered if MR studies are negative and dAVF is still suspected [1,23,29]. MRA head cannot identify bony lesions like jugular fossa dehiscence, SSWA, SSCD, intracranial mass lesions, and venous causes of PT. It is usually combined with MRI head without and with contrast for a better evaluation of intracranial pathologies that can cause PT. MRA Head Without IV Contrast MRA head without IV contrast can diagnose AVM and aberrant ICA but has less sensitivity to diagnose dAVF, smaller AVM, and small glomus tumors. MRA would not be able to diagnose bony lesions like jugular fossa dehiscence, SSWA, and SSCD, intracranial mass lesions, and venous causes of PT. MRA head without IV contrast is usually combined with MRI head with and without IV contrast for a better evaluation of intracranial pathologies, which can cause PT [58]. Source images of 3-D time-of-flight MRA and DSA can detect moderate to high-flow dAVF; however, it is not as sensitive as catheter angiography [59]. Catheter angiography has better sensitivity and may still be considered if MR studies are negative and dAVF is still suspected [1,23,29]. MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of PT.

Tinnitus. Catheter angiography has better sensitivity and may still be considered if MR studies are negative and dAVF is still suspected [1,23,29]. MRA head cannot identify bony lesions like jugular fossa dehiscence, SSWA, SSCD, intracranial mass lesions, and venous causes of PT. It is usually combined with MRI head with and without contrast for a better evaluation of intracranial pathologies which can cause PT. MRA Head Without and With IV Contrast MRA head without and with IV contrast may be used to detect dAVF, AVM, larger glomus jugulare tumors, carotid dissection, and carotid cavernous fistula for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. Catheter angiography has better sensitivity and may still be considered if MR studies are negative and dAVF is still suspected [1,23,29]. MRA head cannot identify bony lesions like jugular fossa dehiscence, SSWA, SSCD, intracranial mass lesions, and venous causes of PT. It is usually combined with MRI head without and with contrast for a better evaluation of intracranial pathologies that can cause PT. MRA Head Without IV Contrast MRA head without IV contrast can diagnose AVM and aberrant ICA but has less sensitivity to diagnose dAVF, smaller AVM, and small glomus tumors. MRA would not be able to diagnose bony lesions like jugular fossa dehiscence, SSWA, and SSCD, intracranial mass lesions, and venous causes of PT. MRA head without IV contrast is usually combined with MRI head with and without IV contrast for a better evaluation of intracranial pathologies, which can cause PT [58]. Source images of 3-D time-of-flight MRA and DSA can detect moderate to high-flow dAVF; however, it is not as sensitive as catheter angiography [59]. Catheter angiography has better sensitivity and may still be considered if MR studies are negative and dAVF is still suspected [1,23,29]. MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of PT.

3094199

acrac_3094199_9

Tinnitus

MRI Head and Internal Auditory Canal Without and With IV Contrast Vascular loops in contact with cranial nerve (CN) VIII are a normal variant and may be seen in up to one-third of normal patients. However, they may contribute to otological symptoms due to neurovascular compression. Patients with PT are 80 times more likely to have vascular loops in contact with CN VIII than patients without PT [60]. Heavily T2-weighted thin-section sequences of MRI head can detect the neurovascular loops in patients with PT [61,62]. Typewriter tinnitus is described as paroxysmal attacks of staccato sounds, thought to be caused by neurovascular compression of the cochlear nerve, and responds well to carbamazepine. MRI can be helpful for detection and evaluation of the extension of the glomus jugulare in the internal jugular vein. Mass lesions in the IAC and posterior fossa such as schwannoma, meningioma, and endolymphatic sac tumor, are readily diagnosed by MRI. Vestibular schwannomas cause NPT more commonly than PT. Other masses can rarely cause tinnitus [49,63,64]. Postgadolinium 3-D images through the brain show detailed anatomy of the transverse and sigmoid dural venous sinuses and can be used to detect the transverse sinus stenosis. The sigmoid sinus diverticulum can also be seen on these images. MRI 4-D flow can detect abnormal flow patterns in the transverse sinuses in patients with venous PT [65]. It was able to detect increased blood flow and blood velocity in patients who had markers of venous PT such as SSWA and transverse sinus stenosis [43]. Tinnitus MRI Head and Internal Auditory Canal Without IV Contrast Vascular loops in contact with CN VIII are a normal variant and may be seen in up to one-third of normal patients. However, they may contribute to otological symptoms due to neurovascular compression. Patients with PT are 80 times more likely to have vascular loops in contact with CN VIII than patients without PT [60].

Tinnitus. MRI Head and Internal Auditory Canal Without and With IV Contrast Vascular loops in contact with cranial nerve (CN) VIII are a normal variant and may be seen in up to one-third of normal patients. However, they may contribute to otological symptoms due to neurovascular compression. Patients with PT are 80 times more likely to have vascular loops in contact with CN VIII than patients without PT [60]. Heavily T2-weighted thin-section sequences of MRI head can detect the neurovascular loops in patients with PT [61,62]. Typewriter tinnitus is described as paroxysmal attacks of staccato sounds, thought to be caused by neurovascular compression of the cochlear nerve, and responds well to carbamazepine. MRI can be helpful for detection and evaluation of the extension of the glomus jugulare in the internal jugular vein. Mass lesions in the IAC and posterior fossa such as schwannoma, meningioma, and endolymphatic sac tumor, are readily diagnosed by MRI. Vestibular schwannomas cause NPT more commonly than PT. Other masses can rarely cause tinnitus [49,63,64]. Postgadolinium 3-D images through the brain show detailed anatomy of the transverse and sigmoid dural venous sinuses and can be used to detect the transverse sinus stenosis. The sigmoid sinus diverticulum can also be seen on these images. MRI 4-D flow can detect abnormal flow patterns in the transverse sinuses in patients with venous PT [65]. It was able to detect increased blood flow and blood velocity in patients who had markers of venous PT such as SSWA and transverse sinus stenosis [43]. Tinnitus MRI Head and Internal Auditory Canal Without IV Contrast Vascular loops in contact with CN VIII are a normal variant and may be seen in up to one-third of normal patients. However, they may contribute to otological symptoms due to neurovascular compression. Patients with PT are 80 times more likely to have vascular loops in contact with CN VIII than patients without PT [60].

3094199

acrac_3094199_10

Tinnitus

Heavily T2- weighted thin-section sequences of MRI head can detect the neurovascular loops in patients with PT [61,62]. Typewriter tinnitus is described as paroxysmal attacks of staccato sounds, thought to be caused by neurovascular compression of the cochlear nerve, and responds well to carbamazepine. MRI without IV contrast can also detect some larger mass lesions like glomus jugulare and AVM that can cause PT. However, absence of contrast would limit its ability to detect smaller masses and AVM. MRV Head With IV Contrast MRV head with IV contrast is a robust tool for detecting stenosis in the transverse sinuses, which could lead to tinnitus in association with IIH. Dural venous sinus stenosis could be from an intrinsic or extrinsic cause [66,67]. The source images can potentially detect a prominent sigmoid sinus diverticulum. However, MRV does not provide bony details to evaluate other pathologies that can cause PT such as sigmoid wall dehiscence and jugular foramen dehiscence. MRV Head Without and With IV Contrast MRV head with IV contrast is a robust tool to detect stenosis in the transverse sinuses, which could lead to tinnitus in association with IIH as described in the previous section. However, MRV does not provide bony details to evaluate other pathologies that can cause PT such as sigmoid wall dehiscence and jugular foramen dehiscence. There is no added benefit in simultaneously performing MRV head without IV contrast also. MRV Head Without IV Contrast MRV head without IV contrast can detect transverse sinus stenosis, but flow-related artifacts can limit optimal evaluation of the transverse sinus stenosis and sigmoid sinus diverticulum [56]. Arachnoid granulations can mimic transverse sinus stenosis. US Duplex Doppler Carotid Artery US duplex Doppler carotid artery is useful to detect atherosclerotic narrowing of the carotids, which is a cause of PT. Atherosclerosis can lead to arterial stiffness, which is also associated with tinnitus [68].

Tinnitus. Heavily T2- weighted thin-section sequences of MRI head can detect the neurovascular loops in patients with PT [61,62]. Typewriter tinnitus is described as paroxysmal attacks of staccato sounds, thought to be caused by neurovascular compression of the cochlear nerve, and responds well to carbamazepine. MRI without IV contrast can also detect some larger mass lesions like glomus jugulare and AVM that can cause PT. However, absence of contrast would limit its ability to detect smaller masses and AVM. MRV Head With IV Contrast MRV head with IV contrast is a robust tool for detecting stenosis in the transverse sinuses, which could lead to tinnitus in association with IIH. Dural venous sinus stenosis could be from an intrinsic or extrinsic cause [66,67]. The source images can potentially detect a prominent sigmoid sinus diverticulum. However, MRV does not provide bony details to evaluate other pathologies that can cause PT such as sigmoid wall dehiscence and jugular foramen dehiscence. MRV Head Without and With IV Contrast MRV head with IV contrast is a robust tool to detect stenosis in the transverse sinuses, which could lead to tinnitus in association with IIH as described in the previous section. However, MRV does not provide bony details to evaluate other pathologies that can cause PT such as sigmoid wall dehiscence and jugular foramen dehiscence. There is no added benefit in simultaneously performing MRV head without IV contrast also. MRV Head Without IV Contrast MRV head without IV contrast can detect transverse sinus stenosis, but flow-related artifacts can limit optimal evaluation of the transverse sinus stenosis and sigmoid sinus diverticulum [56]. Arachnoid granulations can mimic transverse sinus stenosis. US Duplex Doppler Carotid Artery US duplex Doppler carotid artery is useful to detect atherosclerotic narrowing of the carotids, which is a cause of PT. Atherosclerosis can lead to arterial stiffness, which is also associated with tinnitus [68].

3094199

acrac_3094199_11

Tinnitus

Duplex US may be performed when there is a bruit in the neck and carotid stenosis is suspected. However, most other conditions which cause PT cannot be evaluated by US. US can also detect parameters of low flow resistance, high-flow velocity and high-flow volume in external carotid arteries in patients with suspected dAVF as a cause of PT [69]. However, sensitivity is lower than CTA, MRA, and conventional angiography. US Duplex Doppler Transcranial There is no relevant literature to support the use of US duplex Doppler transcranial for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. US Head There is no relevant literature to support the use of US head for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. Variant 2: Pulsatile tinnitus, unilateral or bilateral; suspected retrotympanic lesion on otoscopy. Initial imaging. PT has many causes, and no single imaging study is appropriate for all patients. A diagnostic algorithm based on detailed history and clinical evaluation should progress from less invasive to more invasive imaging studies, and a targeted history and clinical assessment can have implications on the choice of imaging modality [12,19]. Otoscopic examination is extremely useful to guide the correct imaging in evaluation of the PT. When a vascular retrotympanic lesion is seen, the main differential diagnoses are glomus tympanicum, glomus jugulotympanicum, and vascular variants like aberrant ICA, dehiscent jugular foramen, and persistent stapedial artery (PSA). Otosclerosis can also appear as a pinkish retrotympanic lesion (Schwartz sign). It is extremely important to diagnose the vascular variants because inadvertent biopsy can have devastating complications. High-resolution thin-section temporal bone CT (HRCT) without IV contrast has excellent accuracy to make these diagnoses by carefully evaluating the contour of the bone and air spaces. IV contrast is not necessary to diagnose these conditions.

Tinnitus. Duplex US may be performed when there is a bruit in the neck and carotid stenosis is suspected. However, most other conditions which cause PT cannot be evaluated by US. US can also detect parameters of low flow resistance, high-flow velocity and high-flow volume in external carotid arteries in patients with suspected dAVF as a cause of PT [69]. However, sensitivity is lower than CTA, MRA, and conventional angiography. US Duplex Doppler Transcranial There is no relevant literature to support the use of US duplex Doppler transcranial for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. US Head There is no relevant literature to support the use of US head for evaluation of PT when otoscopy does not show a vascular retrotympanic lesion. Variant 2: Pulsatile tinnitus, unilateral or bilateral; suspected retrotympanic lesion on otoscopy. Initial imaging. PT has many causes, and no single imaging study is appropriate for all patients. A diagnostic algorithm based on detailed history and clinical evaluation should progress from less invasive to more invasive imaging studies, and a targeted history and clinical assessment can have implications on the choice of imaging modality [12,19]. Otoscopic examination is extremely useful to guide the correct imaging in evaluation of the PT. When a vascular retrotympanic lesion is seen, the main differential diagnoses are glomus tympanicum, glomus jugulotympanicum, and vascular variants like aberrant ICA, dehiscent jugular foramen, and persistent stapedial artery (PSA). Otosclerosis can also appear as a pinkish retrotympanic lesion (Schwartz sign). It is extremely important to diagnose the vascular variants because inadvertent biopsy can have devastating complications. High-resolution thin-section temporal bone CT (HRCT) without IV contrast has excellent accuracy to make these diagnoses by carefully evaluating the contour of the bone and air spaces. IV contrast is not necessary to diagnose these conditions.

3094199

acrac_3094199_12

Tinnitus

HRCT of the temporal bone would also show some other conditions that cause PT but do not present as a vascular retrotympanic lesion. These conditions include high-riding jugular bulb, jugular bulb diverticulum, SSWA, SSCD, and Paget disease. Tinnitus Arteriography Cervicocerebral There is no relevant literature to support the use of cervicocerebral arteriography for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of PT. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of PT. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of PT. CT Temporal Bone With IV Contrast There is no relevant literature to support the use of CT temporal bone with IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. CT temporal bone without contrast is adequate as described in the next section, and IV contrast does not offer any significant benefits in those indications. Changes in contour of air and bone in the temporal bone study are the key features in making the diagnosis. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of PT. CT Temporal Bone Without IV Contrast CT temporal bone without IV contrast is useful as a first-line imaging modality when a vascular retrotympanic lesion is seen on otoscopic examination. Retrotympanic lesion may be because of a retrotympanic mass such as a glomus tumor (paraganglioma), or vascular variants. It is imperative to distinguish between the two to avoid unnecessary biopsies, which can have devastating complications.

Tinnitus. HRCT of the temporal bone would also show some other conditions that cause PT but do not present as a vascular retrotympanic lesion. These conditions include high-riding jugular bulb, jugular bulb diverticulum, SSWA, SSCD, and Paget disease. Tinnitus Arteriography Cervicocerebral There is no relevant literature to support the use of cervicocerebral arteriography for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of PT. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of PT. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of PT. CT Temporal Bone With IV Contrast There is no relevant literature to support the use of CT temporal bone with IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. CT temporal bone without contrast is adequate as described in the next section, and IV contrast does not offer any significant benefits in those indications. Changes in contour of air and bone in the temporal bone study are the key features in making the diagnosis. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of PT. CT Temporal Bone Without IV Contrast CT temporal bone without IV contrast is useful as a first-line imaging modality when a vascular retrotympanic lesion is seen on otoscopic examination. Retrotympanic lesion may be because of a retrotympanic mass such as a glomus tumor (paraganglioma), or vascular variants. It is imperative to distinguish between the two to avoid unnecessary biopsies, which can have devastating complications.

3094199

acrac_3094199_13

Tinnitus

CT temporal bone without contrast can show masses like glomus tympanicum, otic capsule lesions such as otosclerosis, or vascular variants like aberrant or lateralized internal carotid artery (ICA), PSA, and dehiscent jugular foramen [1,36]. HRCT of the temporal bone can also detect some other conditions that cause PT but do not always present as a vascular retrotympanic mass, such as otospongiosis, Paget disease, sigmoid sinus diverticulum and sigmoid sinus dehiscence, high-riding jugular bulb, and SSCD [39]. Tinnitus Although CTA can detect a lot of the pathologies that can be the cause of PT when there is a retrotympanic vascular lesion, CT of temporal bone can accomplish the same, and perhaps better, because of a smaller field-of-view and higher resolution, and therefore that is preferred over the CTA. CTV Head With IV Contrast Thin-section bone reconstructions from the source images of the CTV provide enough resolution and details to detect bony abnormalities, vascular variants, and glomus tympanicum, which present as vascular retrotympanic lesions. Contrast is not necessary to make diagnosis of aberrant ICA, PSA, high-riding jugular bulb, dehiscent jugular foramen, or glomus tympanicum, because changes in bony and air contour in the temporal bone are sufficient to make a diagnosis. Although CTV can be used for a lot of the pathologies that can be the cause of PT when there is a retrotympanic vascular lesion, CT of temporal bone can accomplish the same, and perhaps better, because of a smaller field-of-view and higher resolution, and therefore that is preferred over the CTV. MRA Head With IV Contrast There is no relevant literature to support the use of MRA head with IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. Aberrant ICA can be diagnosed by MRA head with IV contrast.

Tinnitus. CT temporal bone without contrast can show masses like glomus tympanicum, otic capsule lesions such as otosclerosis, or vascular variants like aberrant or lateralized internal carotid artery (ICA), PSA, and dehiscent jugular foramen [1,36]. HRCT of the temporal bone can also detect some other conditions that cause PT but do not always present as a vascular retrotympanic mass, such as otospongiosis, Paget disease, sigmoid sinus diverticulum and sigmoid sinus dehiscence, high-riding jugular bulb, and SSCD [39]. Tinnitus Although CTA can detect a lot of the pathologies that can be the cause of PT when there is a retrotympanic vascular lesion, CT of temporal bone can accomplish the same, and perhaps better, because of a smaller field-of-view and higher resolution, and therefore that is preferred over the CTA. CTV Head With IV Contrast Thin-section bone reconstructions from the source images of the CTV provide enough resolution and details to detect bony abnormalities, vascular variants, and glomus tympanicum, which present as vascular retrotympanic lesions. Contrast is not necessary to make diagnosis of aberrant ICA, PSA, high-riding jugular bulb, dehiscent jugular foramen, or glomus tympanicum, because changes in bony and air contour in the temporal bone are sufficient to make a diagnosis. Although CTV can be used for a lot of the pathologies that can be the cause of PT when there is a retrotympanic vascular lesion, CT of temporal bone can accomplish the same, and perhaps better, because of a smaller field-of-view and higher resolution, and therefore that is preferred over the CTV. MRA Head With IV Contrast There is no relevant literature to support the use of MRA head with IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. Aberrant ICA can be diagnosed by MRA head with IV contrast.

3094199

acrac_3094199_14

Tinnitus

However, it is not a good test to diagnose other conditions like glomus tympanicum, PSA, glomus jugulotympanicum, or dehiscent jugular foramen, which can present as vascular retrotympanic lesions. MRA Head Without and With IV Contrast There is no relevant literature to support the use of MRA head without and with IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. MRA Head Without IV Contrast There is no relevant literature to support the use of MRA head without IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. Aberrant ICA can be diagnosed by MRA head without IV contrast. However, it is not a good test to diagnose other conditions like glomus tympanicum, PSA, glomus jugulotympanicum, or dehiscent jugular foramen, which can present as vascular retrotympanic lesions. MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. MRI Head and Internal Auditory Canal Without and With IV Contrast The usual etiologies for vascular retrotympanic lesions are glomus tympanicum, glomus jugulotympanicum, aberrant ICA, PSA, and dehiscent jugular bulb. Small glomus tympanicum and glomus jugulotympanicum may be difficult to see on the MRI head and are easily seen on the CT temporal bone. There is no relevant literature to support the use of MRI head for detection of vascular variants that may present as vascular retrotympanic lesions. MRI Head and Internal Auditory Canal Without IV Contrast The usual etiologies for vascular retrotympanic lesions are glomus tympanicum, glomus jugulotympanicum, aberrant ICA, PSA, and dehiscent jugular bulb. Tiny glomus tympanicum may be difficult to see on the MRI head and are easily seen on the CT temporal bone. There is no relevant literature to support the use of MRI head for detection of vascular variants that may present as vascular retrotympanic lesions.

Tinnitus. However, it is not a good test to diagnose other conditions like glomus tympanicum, PSA, glomus jugulotympanicum, or dehiscent jugular foramen, which can present as vascular retrotympanic lesions. MRA Head Without and With IV Contrast There is no relevant literature to support the use of MRA head without and with IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. MRA Head Without IV Contrast There is no relevant literature to support the use of MRA head without IV contrast for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. Aberrant ICA can be diagnosed by MRA head without IV contrast. However, it is not a good test to diagnose other conditions like glomus tympanicum, PSA, glomus jugulotympanicum, or dehiscent jugular foramen, which can present as vascular retrotympanic lesions. MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. MRI Head and Internal Auditory Canal Without and With IV Contrast The usual etiologies for vascular retrotympanic lesions are glomus tympanicum, glomus jugulotympanicum, aberrant ICA, PSA, and dehiscent jugular bulb. Small glomus tympanicum and glomus jugulotympanicum may be difficult to see on the MRI head and are easily seen on the CT temporal bone. There is no relevant literature to support the use of MRI head for detection of vascular variants that may present as vascular retrotympanic lesions. MRI Head and Internal Auditory Canal Without IV Contrast The usual etiologies for vascular retrotympanic lesions are glomus tympanicum, glomus jugulotympanicum, aberrant ICA, PSA, and dehiscent jugular bulb. Tiny glomus tympanicum may be difficult to see on the MRI head and are easily seen on the CT temporal bone. There is no relevant literature to support the use of MRI head for detection of vascular variants that may present as vascular retrotympanic lesions.

3094199

acrac_3094199_15

Tinnitus

MRV Head With IV Contrast There is no relevant literature to support the use of MRV head with IV contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. MRV Head Without and With IV Contrast There is no relevant literature to support the use of MRV head without and with IV contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. MRV Head Without IV Contrast There is no relevant literature to support the use of MRV head without contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. US Duplex Doppler Carotid Artery There is no relevant literature to support the use of US duplex doppler carotid artery for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. Tinnitus US Duplex Doppler Transcranial There is no relevant literature to support the use of US duplex doppler transcranial for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. US Head There is no relevant literature to support the use of US head for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. Arteriography Cervicocerebral There is no relevant literature to support the use of conventional arteriography for evaluation of unilateral NPT. CT Head with IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of unilateral NPT. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of unilateral NPT. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of unilateral NPT. CT Temporal Bone With IV Contrast CT temporal bone with IV contrast may be considered in a few patients if they need imaging to evaluate for retrocochlear pathology and MRI cannot be performed. Larger mass lesions such as vestibular schwannomas and meningiomas can be seen.

Tinnitus. MRV Head With IV Contrast There is no relevant literature to support the use of MRV head with IV contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. MRV Head Without and With IV Contrast There is no relevant literature to support the use of MRV head without and with IV contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. MRV Head Without IV Contrast There is no relevant literature to support the use of MRV head without contrast for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. US Duplex Doppler Carotid Artery There is no relevant literature to support the use of US duplex doppler carotid artery for evaluation of PT when a retrotympanic lesion is suspected on otoscopy. Tinnitus US Duplex Doppler Transcranial There is no relevant literature to support the use of US duplex doppler transcranial for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. US Head There is no relevant literature to support the use of US head for evaluation of PT when otoscopy shows a vascular retrotympanic lesion. Arteriography Cervicocerebral There is no relevant literature to support the use of conventional arteriography for evaluation of unilateral NPT. CT Head with IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of unilateral NPT. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of unilateral NPT. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of unilateral NPT. CT Temporal Bone With IV Contrast CT temporal bone with IV contrast may be considered in a few patients if they need imaging to evaluate for retrocochlear pathology and MRI cannot be performed. Larger mass lesions such as vestibular schwannomas and meningiomas can be seen.

3094199

acrac_3094199_16

Tinnitus

However, small lesions, especially when located in the IAC rather than the cerebellopontine angle cistern, can be missed on CT because of the limited contrast resolution. Middle ear adenomatous tumors are rare tumors in the middle ear that can cause NPT. They show significant contrast enhancement on CT and MRI but no vascular blush on angiography [70]. Otoscopic examination reveals a retrotympanic mass. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of unilateral NPT. CT Temporal Bone Without IV Contrast CT can diagnose cochlear nerve aperture stenosis, which is associated with cochlear nerve hypoplasia, a condition in which patients can present with sensorineural hearing loss and tinnitus [75]. CT temporal bone is considered if Tinnitus chronic inflammation in the middle ear is suspected to differentiate otitis media from cholesteatoma [76]. It can also be considered for abnormalities of the vestibular aqueduct. CTA Head and Neck With IV Contrast There is no relevant literature to support the use of CTA head and neck with IV contrast for evaluation of unilateral NPT. CTA Head With IV Contrast There is no relevant literature to support the use of CTA head with IV contrast for routine evaluation of unilateral NPT. CTV Head With IV Contrast There is no relevant literature to support the use of CTV head with IV contrast for evaluation of unilateral NPT. MRA Head With IV Contrast There is no relevant literature to support the use of MRA head with IV contrast for evaluation of unilateral NPT. MRA Head Without and With IV Contrast There is no relevant literature to support the use of MRA head without and with IV contrast for evaluation of unilateral NPT. MRA Head Without IV Contrast There is no relevant literature to support the use of MRA head without IV contrast for evaluation of unilateral NPT.

Tinnitus. However, small lesions, especially when located in the IAC rather than the cerebellopontine angle cistern, can be missed on CT because of the limited contrast resolution. Middle ear adenomatous tumors are rare tumors in the middle ear that can cause NPT. They show significant contrast enhancement on CT and MRI but no vascular blush on angiography [70]. Otoscopic examination reveals a retrotympanic mass. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of unilateral NPT. CT Temporal Bone Without IV Contrast CT can diagnose cochlear nerve aperture stenosis, which is associated with cochlear nerve hypoplasia, a condition in which patients can present with sensorineural hearing loss and tinnitus [75]. CT temporal bone is considered if Tinnitus chronic inflammation in the middle ear is suspected to differentiate otitis media from cholesteatoma [76]. It can also be considered for abnormalities of the vestibular aqueduct. CTA Head and Neck With IV Contrast There is no relevant literature to support the use of CTA head and neck with IV contrast for evaluation of unilateral NPT. CTA Head With IV Contrast There is no relevant literature to support the use of CTA head with IV contrast for routine evaluation of unilateral NPT. CTV Head With IV Contrast There is no relevant literature to support the use of CTV head with IV contrast for evaluation of unilateral NPT. MRA Head With IV Contrast There is no relevant literature to support the use of MRA head with IV contrast for evaluation of unilateral NPT. MRA Head Without and With IV Contrast There is no relevant literature to support the use of MRA head without and with IV contrast for evaluation of unilateral NPT. MRA Head Without IV Contrast There is no relevant literature to support the use of MRA head without IV contrast for evaluation of unilateral NPT.

3094199

acrac_3094199_17

Tinnitus

MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of unilateral NPT. The study should be performed without and with IV contrast as described in the next section. MRI Head and Internal Auditory Canal Without and With IV Contrast MRI head and IAC without and with IV contrast can be considered for retrocochlear processes such as vestibular schwannoma or other mass lesions in patients with NPT [71,77]. Tinnitus may occur among patients with vestibular schwannomas (63%-75%) and intralabyrinthine schwannomas [78]. These are readily diagnosed by MRI. Rarely, meningiomas in or around the IAC and cerebellopontine angle cistern can also cause tinnitus and are accurately diagnosed on MRI [79,80]. Vestibular schwannomas cause NPT more commonly than PT [49]. Mass lesions in the IAC and posterior fossa such as schwannomas, meningiomas, and endolymphatic sac tumors are readily diagnosed by MRI. A study of 218 patients with NPT found that 91.8% of patients had an unremarkable MRI [81]. Spontaneous intracranial hypotension can cause tinnitus, probably due to venous engorgement in the IAC [82,83]. Endolymphatic hydrops has an association with Meniere disease, which presents with episodic hearing loss, vertigo, and tinnitus [84-87] and requires special sequences for diagnosis, including heavily T2-weighted 3-D FLAIR (fluid- attenuated inversion recovery) and 3-D real inversion recovery performed 4 hours after injection of the IV contrast [88], best interpreted alongside a routine 3-D heavily T2-weighted sequence. MRV Head With IV Contrast There is no relevant literature to support the use of MRV head with IV contrast for evaluation of unilateral NPT. MRV Head Without and With IV Contrast There is no relevant literature to support the use of MRV head without and with IV contrast for evaluation of unilateral NPT.

Tinnitus. MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of unilateral NPT. The study should be performed without and with IV contrast as described in the next section. MRI Head and Internal Auditory Canal Without and With IV Contrast MRI head and IAC without and with IV contrast can be considered for retrocochlear processes such as vestibular schwannoma or other mass lesions in patients with NPT [71,77]. Tinnitus may occur among patients with vestibular schwannomas (63%-75%) and intralabyrinthine schwannomas [78]. These are readily diagnosed by MRI. Rarely, meningiomas in or around the IAC and cerebellopontine angle cistern can also cause tinnitus and are accurately diagnosed on MRI [79,80]. Vestibular schwannomas cause NPT more commonly than PT [49]. Mass lesions in the IAC and posterior fossa such as schwannomas, meningiomas, and endolymphatic sac tumors are readily diagnosed by MRI. A study of 218 patients with NPT found that 91.8% of patients had an unremarkable MRI [81]. Spontaneous intracranial hypotension can cause tinnitus, probably due to venous engorgement in the IAC [82,83]. Endolymphatic hydrops has an association with Meniere disease, which presents with episodic hearing loss, vertigo, and tinnitus [84-87] and requires special sequences for diagnosis, including heavily T2-weighted 3-D FLAIR (fluid- attenuated inversion recovery) and 3-D real inversion recovery performed 4 hours after injection of the IV contrast [88], best interpreted alongside a routine 3-D heavily T2-weighted sequence. MRV Head With IV Contrast There is no relevant literature to support the use of MRV head with IV contrast for evaluation of unilateral NPT. MRV Head Without and With IV Contrast There is no relevant literature to support the use of MRV head without and with IV contrast for evaluation of unilateral NPT.

3094199

acrac_3094199_18

Tinnitus

MRV Head Without IV Contrast There is no relevant literature to support the use of MRV head without IV contrast for evaluation of unilateral NPT. Tinnitus US Duplex Doppler Carotid Artery There is no relevant literature to support the use of US duplex Doppler carotid artery for evaluation of unilateral NPT. US Duplex Doppler Transcranial There is no relevant literature to support the use of US duplex Doppler transcranial for evaluation of unilateral NPT. US Head There is no relevant literature to support the use of US head for evaluation of unilateral NPT. Variant 4: Nonpulsatile tinnitus, bilateral; no hearing loss, and no neurologic deficit, and no trauma. Initial imaging. Imaging is not helpful in cases of bilateral NPT related to age-related hearing loss, prior exposure to noise, acoustic trauma, ototoxic medications, and chronic bilateral hearing loss [92]. Most cases of bilateral NPT are associated with sensorineural hearing loss, and imaging is typically unrevealing in such cases [34,93,94]. The AAO-HNS guidelines make a strong recommendation against any imaging studies of the head and neck for the subset of patients in whom tinnitus does not localize to 1 ear, is nonpulsatile, and is not associated with focal neurological abnormalities or an asymmetric hearing loss [6,7]. Arteriography Cervicocerebral There is no relevant literature to support the use of conventional arteriography for evaluation of bilateral NPT. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of bilateral NPT. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of bilateral NPT. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of bilateral NPT.

Tinnitus. MRV Head Without IV Contrast There is no relevant literature to support the use of MRV head without IV contrast for evaluation of unilateral NPT. Tinnitus US Duplex Doppler Carotid Artery There is no relevant literature to support the use of US duplex Doppler carotid artery for evaluation of unilateral NPT. US Duplex Doppler Transcranial There is no relevant literature to support the use of US duplex Doppler transcranial for evaluation of unilateral NPT. US Head There is no relevant literature to support the use of US head for evaluation of unilateral NPT. Variant 4: Nonpulsatile tinnitus, bilateral; no hearing loss, and no neurologic deficit, and no trauma. Initial imaging. Imaging is not helpful in cases of bilateral NPT related to age-related hearing loss, prior exposure to noise, acoustic trauma, ototoxic medications, and chronic bilateral hearing loss [92]. Most cases of bilateral NPT are associated with sensorineural hearing loss, and imaging is typically unrevealing in such cases [34,93,94]. The AAO-HNS guidelines make a strong recommendation against any imaging studies of the head and neck for the subset of patients in whom tinnitus does not localize to 1 ear, is nonpulsatile, and is not associated with focal neurological abnormalities or an asymmetric hearing loss [6,7]. Arteriography Cervicocerebral There is no relevant literature to support the use of conventional arteriography for evaluation of bilateral NPT. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast for evaluation of bilateral NPT. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast for evaluation of bilateral NPT. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast for evaluation of bilateral NPT.

3094199

acrac_3094199_19

Tinnitus

CT Temporal Bone With IV Contrast There is no relevant literature to support the use of CT temporal bone with IV contrast for evaluation of bilateral NPT. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of bilateral NPT. CT Temporal Bone Without IV Contrast There is no relevant literature to support the use of CT temporal bone without IV contrast for evaluation of bilateral NPT. CTA Head and Neck With IV Contrast There is no relevant literature to support the use of CTA head and neck with IV contrast for evaluation of bilateral NPT. CTA Head With IV Contrast There is no relevant literature to support the use of CTA head with IV contrast for evaluation of bilateral NPT. CTV Head With IV Contrast There is no relevant literature to support the use of CTV head with iv contrast for evaluation of bilateral NPT. MRA Head With IV Contrast There is no relevant literature to support the use of MRA head with IV contrast for evaluation of bilateral NPT. Tinnitus MRA Head Without and With IV Contrast There is no relevant literature to support the use of MRA head without and with IV contrast for evaluation of bilateral NPT. MRA Head Without IV Contrast There is no relevant literature to support the use of MRA head without IV contrast for evaluation of bilateral NPT. MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of bilateral NPT. MRI Head and Internal Auditory Canal Without and With IV Contrast There is no relevant literature to support the use of MRI head and IAC without and with IV contrast for evaluation of bilateral NPT. MRI Head and Internal Auditory Canal Without IV Contrast There is no relevant literature to support the use of MRI head and IAC without IV contrast for evaluation of bilateral NPT.

Tinnitus. CT Temporal Bone With IV Contrast There is no relevant literature to support the use of CT temporal bone with IV contrast for evaluation of bilateral NPT. CT Temporal Bone Without and With IV Contrast There is no relevant literature to support the use of CT temporal bone without and with IV contrast for evaluation of bilateral NPT. CT Temporal Bone Without IV Contrast There is no relevant literature to support the use of CT temporal bone without IV contrast for evaluation of bilateral NPT. CTA Head and Neck With IV Contrast There is no relevant literature to support the use of CTA head and neck with IV contrast for evaluation of bilateral NPT. CTA Head With IV Contrast There is no relevant literature to support the use of CTA head with IV contrast for evaluation of bilateral NPT. CTV Head With IV Contrast There is no relevant literature to support the use of CTV head with iv contrast for evaluation of bilateral NPT. MRA Head With IV Contrast There is no relevant literature to support the use of MRA head with IV contrast for evaluation of bilateral NPT. Tinnitus MRA Head Without and With IV Contrast There is no relevant literature to support the use of MRA head without and with IV contrast for evaluation of bilateral NPT. MRA Head Without IV Contrast There is no relevant literature to support the use of MRA head without IV contrast for evaluation of bilateral NPT. MRI Head and Internal Auditory Canal With IV Contrast There is no relevant literature to support the use of MRI head and IAC with IV contrast for evaluation of bilateral NPT. MRI Head and Internal Auditory Canal Without and With IV Contrast There is no relevant literature to support the use of MRI head and IAC without and with IV contrast for evaluation of bilateral NPT. MRI Head and Internal Auditory Canal Without IV Contrast There is no relevant literature to support the use of MRI head and IAC without IV contrast for evaluation of bilateral NPT.

3094199

acrac_69364_0

Post Treatment Surveillance of Bladder Cancer

Introduction/Background Urothelial carcinoma (UC), previously known as transitional cell carcinoma, accounts for >90% of all urinary bladder cancers in the United States. In the genitourinary tract, UC is the second most common cancer and cause of cancer death [1]. The American Cancer Society estimated that there will be 81,400 new cases of bladder cancer and 17,980 deaths related to bladder cancer in 2020 [1]. Bladder cancer staging is based on the American Joint Committee on Cancer Tumor, Node, Metastasis system, and T-stage (depth of invasion) is used to differentiate patients into 2 groups: nonmuscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) [2]. NMIBC accounts for 75% of bladder cancers and consists of a heterogeneous group of tumors that includes superficial papillary tumors (Ta), carcinoma in situ (Tis), and tumors invading the lamina propria (T1), all with different rates of recurrence and progression [2]. MIBC consists of tumors that invade the muscularis propria (T2) and beyond, and these tumors have a significantly higher rate of recurrence and progression after treatment. The 5- year survival rate for all stages of UC of the urinary bladder combined is 78% [1]. For NMIBC stages 0 and I, the 5-year survival rates are 95% and 75%, respectively; 5-year survival rates drop to 70%, 35%, and 5% for MIBC at stages II, III, and IV, respectively [1]. Reprint requests to: [email protected] Post-Treatment Surveillance of Bladder Cancer The AUA/SUO and National Comprehensive Cancer Network (NCCN) guidelines differ slightly in imaging recommendations following treatment for NMIBC. The NCCN guidelines recommend upper-tract surveillance imaging for patients at low or intermediate risk, as clinically indicated, and scheduled upper-tract imaging every 1 to 2 years for patients at high risk [17]. The AUA/SUO guidelines recommend upper-tract surveillance imaging patients at both intermediate and high risk at 1 to 2 year intervals [4].

Post Treatment Surveillance of Bladder Cancer. Introduction/Background Urothelial carcinoma (UC), previously known as transitional cell carcinoma, accounts for >90% of all urinary bladder cancers in the United States. In the genitourinary tract, UC is the second most common cancer and cause of cancer death [1]. The American Cancer Society estimated that there will be 81,400 new cases of bladder cancer and 17,980 deaths related to bladder cancer in 2020 [1]. Bladder cancer staging is based on the American Joint Committee on Cancer Tumor, Node, Metastasis system, and T-stage (depth of invasion) is used to differentiate patients into 2 groups: nonmuscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) [2]. NMIBC accounts for 75% of bladder cancers and consists of a heterogeneous group of tumors that includes superficial papillary tumors (Ta), carcinoma in situ (Tis), and tumors invading the lamina propria (T1), all with different rates of recurrence and progression [2]. MIBC consists of tumors that invade the muscularis propria (T2) and beyond, and these tumors have a significantly higher rate of recurrence and progression after treatment. The 5- year survival rate for all stages of UC of the urinary bladder combined is 78% [1]. For NMIBC stages 0 and I, the 5-year survival rates are 95% and 75%, respectively; 5-year survival rates drop to 70%, 35%, and 5% for MIBC at stages II, III, and IV, respectively [1]. Reprint requests to: [email protected] Post-Treatment Surveillance of Bladder Cancer The AUA/SUO and National Comprehensive Cancer Network (NCCN) guidelines differ slightly in imaging recommendations following treatment for NMIBC. The NCCN guidelines recommend upper-tract surveillance imaging for patients at low or intermediate risk, as clinically indicated, and scheduled upper-tract imaging every 1 to 2 years for patients at high risk [17]. The AUA/SUO guidelines recommend upper-tract surveillance imaging patients at both intermediate and high risk at 1 to 2 year intervals [4].

69364

acrac_69364_1

Post Treatment Surveillance of Bladder Cancer

For the purposes of this manuscript, NMIBC has been divided into 2 categories: NMIBC without symptoms or risk factors (low-risk patients) and NMIBC with symptoms or risk factors (intermediate- and high-risk patients). Local practice patterns (NCCN versus AUA/SUO) should determine whether upper-tract surveillance should be considered in patients with intermediate risk and no symptoms. Special Imaging Considerations Cystoscopic and Virtual Cystoscopic Surveillance Patients with NMIBC undergo routine surveillance cystoscopy to assess for recurrence and progression to MIBC. As cystoscopy is a relatively invasive procedure, there was previous interest in developing virtual cystoscopic or cystographic techniques using CT or MRI, particularly for problem solving and for cases in which conventional cystoscopy is difficult, such as for the evaluation of narrow-necked diverticula. CT cystography, following the instillation of air, saline, or water-soluble contrast into the urinary bladder via a Foley catheter, and MRI evaluation of the urinary bladder with virtual cystoscopy (3-D fly through) and cystography (T2-weighted turbo spin-echo imaging) are not commonly performed and do not eliminate the need for conventional cystoscopy. CTU CTU CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts. There is variability in the specific parameters, but it usually involves unenhanced images followed by intravenous (IV) contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum-intensity projection or 3-D volume rendering.

Post Treatment Surveillance of Bladder Cancer. For the purposes of this manuscript, NMIBC has been divided into 2 categories: NMIBC without symptoms or risk factors (low-risk patients) and NMIBC with symptoms or risk factors (intermediate- and high-risk patients). Local practice patterns (NCCN versus AUA/SUO) should determine whether upper-tract surveillance should be considered in patients with intermediate risk and no symptoms. Special Imaging Considerations Cystoscopic and Virtual Cystoscopic Surveillance Patients with NMIBC undergo routine surveillance cystoscopy to assess for recurrence and progression to MIBC. As cystoscopy is a relatively invasive procedure, there was previous interest in developing virtual cystoscopic or cystographic techniques using CT or MRI, particularly for problem solving and for cases in which conventional cystoscopy is difficult, such as for the evaluation of narrow-necked diverticula. CT cystography, following the instillation of air, saline, or water-soluble contrast into the urinary bladder via a Foley catheter, and MRI evaluation of the urinary bladder with virtual cystoscopy (3-D fly through) and cystography (T2-weighted turbo spin-echo imaging) are not commonly performed and do not eliminate the need for conventional cystoscopy. CTU CTU CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts. There is variability in the specific parameters, but it usually involves unenhanced images followed by intravenous (IV) contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum-intensity projection or 3-D volume rendering.

69364

acrac_69364_2

Post Treatment Surveillance of Bladder Cancer

For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast. CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the precontrast and excretory phases. MRU MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phase. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract. Discussion of Procedures by Variant Variant 1: Nonmuscle invasive bladder cancer with no symptoms or risk factors. Post-treatment surveillance. In patients with NMIBC without symptoms or risk factors, metastatic disease is uncommon, thus screening for distant metastatic disease is not recommended. Bladder recurrence is common following treatment for NMIBC. In a study of 190 patients with low-grade Ta disease, bladder cancer recurrence was identified in 43.2% (82 of 190) Post-Treatment Surveillance of Bladder Cancer of patients; however, progression to MIBC was seen in only 2 patients [18]. The incidence of upper-tract UC (UTUC) in this patient population is 0.6% to 0.9% [19,20].

Post Treatment Surveillance of Bladder Cancer. For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast. CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the precontrast and excretory phases. MRU MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phase. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract. Discussion of Procedures by Variant Variant 1: Nonmuscle invasive bladder cancer with no symptoms or risk factors. Post-treatment surveillance. In patients with NMIBC without symptoms or risk factors, metastatic disease is uncommon, thus screening for distant metastatic disease is not recommended. Bladder recurrence is common following treatment for NMIBC. In a study of 190 patients with low-grade Ta disease, bladder cancer recurrence was identified in 43.2% (82 of 190) Post-Treatment Surveillance of Bladder Cancer of patients; however, progression to MIBC was seen in only 2 patients [18]. The incidence of upper-tract UC (UTUC) in this patient population is 0.6% to 0.9% [19,20].

69364

acrac_69364_3

Post Treatment Surveillance of Bladder Cancer

Routine surveillance of the upper urinary tract in asymptomatic, low-risk patients is not recommended. Urine cytological analysis and cystoscopy are performed routinely in the setting of NMIBC and are felt to be sufficiently accurate for the diagnosis of bladder cancer recurrent in this patient population [4,21,22]. CT Abdomen and Pelvis In patients with NMIBC without risk factors or symptoms, screening for distant metastatic disease with cross- sectional imaging (CT abdomen and pelvis without or with IV contrast) is not supported. CT Chest Chest CT is generally not appropriate for patients with NMIBC without symptoms or risk factors. CTU CTU CTU is a primary imaging test for comprehensive evaluation of the genitourinary tract that can be used to identify metastatic disease and metachronous UC. In the setting of NMIBC without symptoms or risk factors, metastatic disease is uncommon; thus, screening for distant metastatic disease is not supported. Although bladder recurrence is common, CT is not supported to screen for bladder recurrence, and it is generally felt that urine cytological evaluation and cystoscopy are sufficiently accurate for the diagnosis of bladder recurrence in this patient population. The incidence of UTUC in this patient population is 0.6% to 0.9% [19,20]. In addition, in a study of 935 patients with history of NMIBC, only 29% (15 of 51) of UTUCs were diagnosed on routine imaging while the remaining UTUCs were diagnosed once patients became symptomatic, for an overall imaging efficacy of 0.49% (15 UTUC out of 3,074 CT examinations) [23]. Routine surveillance of the upper urinary tract in asymptomatic, low-risk patients is not supported. FDG-PET/CT Skull Base to Mid-Thigh Imaging with PET using the tracer fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)/CT is generally not appropriate for patients with NMIBC without symptoms or risk factors. The risk of metastatic disease is extremely low.

Post Treatment Surveillance of Bladder Cancer. Routine surveillance of the upper urinary tract in asymptomatic, low-risk patients is not recommended. Urine cytological analysis and cystoscopy are performed routinely in the setting of NMIBC and are felt to be sufficiently accurate for the diagnosis of bladder cancer recurrent in this patient population [4,21,22]. CT Abdomen and Pelvis In patients with NMIBC without risk factors or symptoms, screening for distant metastatic disease with cross- sectional imaging (CT abdomen and pelvis without or with IV contrast) is not supported. CT Chest Chest CT is generally not appropriate for patients with NMIBC without symptoms or risk factors. CTU CTU CTU is a primary imaging test for comprehensive evaluation of the genitourinary tract that can be used to identify metastatic disease and metachronous UC. In the setting of NMIBC without symptoms or risk factors, metastatic disease is uncommon; thus, screening for distant metastatic disease is not supported. Although bladder recurrence is common, CT is not supported to screen for bladder recurrence, and it is generally felt that urine cytological evaluation and cystoscopy are sufficiently accurate for the diagnosis of bladder recurrence in this patient population. The incidence of UTUC in this patient population is 0.6% to 0.9% [19,20]. In addition, in a study of 935 patients with history of NMIBC, only 29% (15 of 51) of UTUCs were diagnosed on routine imaging while the remaining UTUCs were diagnosed once patients became symptomatic, for an overall imaging efficacy of 0.49% (15 UTUC out of 3,074 CT examinations) [23]. Routine surveillance of the upper urinary tract in asymptomatic, low-risk patients is not supported. FDG-PET/CT Skull Base to Mid-Thigh Imaging with PET using the tracer fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)/CT is generally not appropriate for patients with NMIBC without symptoms or risk factors. The risk of metastatic disease is extremely low.

69364

acrac_69364_4

Post Treatment Surveillance of Bladder Cancer

FDG is excreted by the kidneys, and activity obscures evaluation of the upper and lower urinary tract for recurrent disease. MRI Abdomen and Pelvis In patients with NMIBC without risk factors or symptoms, screening for distant metastatic disease with cross- sectional imaging is not supported. There has been increasing interest in using MRI for local staging of bladder cancer in the pretreatment setting [24- 28]. However, progression to MIBC in this patient population is rare. MRI has been used to evaluate the urinary bladder following transurethral resection of bladder tumor (TURBT). In a study including 47 patients with recurrent bladder cancer, MRI demonstrated a sensitivity of 67% and 73% and a specificity of 81% and 62% for 2 readers, respectively, and false-negatives included low-grade Ta lesions [29]. In another study, diffusion-weighted imaging (DWI) had a sensitivity of 100% and specificity of 81.8% for recurrent tumor in 11 patients [30]. Despite these results, there is limited data for using MRI as a screening test in patients with previously treated bladder cancer. At this time, it is generally felt that urine cytological evaluation and conventional cystoscopy are sufficiently accurate for the diagnosis of bladder recurrence in this patient population. MRU MRU can be used as a primary imaging test for comprehensive evaluation of the genitourinary tract that can be used to identify metastatic disease and metachronous UC. Currently, evaluation for metastatic disease and routine surveillance of the upper urinary tract in asymptomatic, low-risk patients is not supported. Although MRU has been shown to have a sensitivity of 63% and specificity of 91% in a small study of 35 patients with suspected UTUC, the incidence of UTUC in this patient population is only between 0.6% and 0.9% [19,20,31]. Radiography Chest Chest radiography is generally not appropriate for patients with NMIBC without symptoms or risk factors.

Post Treatment Surveillance of Bladder Cancer. FDG is excreted by the kidneys, and activity obscures evaluation of the upper and lower urinary tract for recurrent disease. MRI Abdomen and Pelvis In patients with NMIBC without risk factors or symptoms, screening for distant metastatic disease with cross- sectional imaging is not supported. There has been increasing interest in using MRI for local staging of bladder cancer in the pretreatment setting [24- 28]. However, progression to MIBC in this patient population is rare. MRI has been used to evaluate the urinary bladder following transurethral resection of bladder tumor (TURBT). In a study including 47 patients with recurrent bladder cancer, MRI demonstrated a sensitivity of 67% and 73% and a specificity of 81% and 62% for 2 readers, respectively, and false-negatives included low-grade Ta lesions [29]. In another study, diffusion-weighted imaging (DWI) had a sensitivity of 100% and specificity of 81.8% for recurrent tumor in 11 patients [30]. Despite these results, there is limited data for using MRI as a screening test in patients with previously treated bladder cancer. At this time, it is generally felt that urine cytological evaluation and conventional cystoscopy are sufficiently accurate for the diagnosis of bladder recurrence in this patient population. MRU MRU can be used as a primary imaging test for comprehensive evaluation of the genitourinary tract that can be used to identify metastatic disease and metachronous UC. Currently, evaluation for metastatic disease and routine surveillance of the upper urinary tract in asymptomatic, low-risk patients is not supported. Although MRU has been shown to have a sensitivity of 63% and specificity of 91% in a small study of 35 patients with suspected UTUC, the incidence of UTUC in this patient population is only between 0.6% and 0.9% [19,20,31]. Radiography Chest Chest radiography is generally not appropriate for patients with NMIBC without symptoms or risk factors.

69364

acrac_69364_5

Post Treatment Surveillance of Bladder Cancer

Radiography Intravenous Urography CTU and, to a lesser extent, MRU have replaced IV urography (IVU) for the evaluation of the upper urinary tract. IVU does not have a current role in surveillance of NMIBC. Post-Treatment Surveillance of Bladder Cancer US Pelvis (Bladder) Because cystoscopy is relatively invasive and time consuming, there is interest in noninvasive and effective imaging modalities to identify recurrent bladder cancer. In a small prospective study, transabdominal ultrasound (US) was found to have a sensitivity of 78.5% and specificity of 100% for the diagnosis of recurrent UC of the urinary bladder, with cystoscopy as the reference standard [32]. In this study, US accurately diagnosed bladder cancer in 78.6% (11 of 14) of patients, missing 2 tumors <3 mm and 1 lesion located in a diverticulum. In another study, the combination of grayscale US, multiplanar reconstruction, and 3-D virtual US had a sensitivity of 96.4% and specificity of 88.8% compared with conventional cystoscopy [33]. Despite these results, it is generally understood that US has limited ability to identify MIBC in clinical practice and is sparingly used. As cystoscopy allows identification of recurrent neoplasm, concurrent biopsy, and local staging, US has not replaced the need for conventional cystoscopic surveillance for patients with NMIBC. Variant 2: Nonmuscle invasive bladder cancer with symptoms or risk factors. Post-treatment surveillance. Patients with NMIBC and risk factors require frequent surveillance for recurrent bladder cancer, which is generally done with conventional cystoscopy. In patients at intermediate risk with a history of TURBT and intravesical chemotherapy, recurrent bladder cancer is identified in up to 57% (413 of 724) of patients [8]. In patients at high risk, 59.6% (2,694 of 4,521) of patients develop multiple recurrences within 2 years of initial treatment [34].

Post Treatment Surveillance of Bladder Cancer. Radiography Intravenous Urography CTU and, to a lesser extent, MRU have replaced IV urography (IVU) for the evaluation of the upper urinary tract. IVU does not have a current role in surveillance of NMIBC. Post-Treatment Surveillance of Bladder Cancer US Pelvis (Bladder) Because cystoscopy is relatively invasive and time consuming, there is interest in noninvasive and effective imaging modalities to identify recurrent bladder cancer. In a small prospective study, transabdominal ultrasound (US) was found to have a sensitivity of 78.5% and specificity of 100% for the diagnosis of recurrent UC of the urinary bladder, with cystoscopy as the reference standard [32]. In this study, US accurately diagnosed bladder cancer in 78.6% (11 of 14) of patients, missing 2 tumors <3 mm and 1 lesion located in a diverticulum. In another study, the combination of grayscale US, multiplanar reconstruction, and 3-D virtual US had a sensitivity of 96.4% and specificity of 88.8% compared with conventional cystoscopy [33]. Despite these results, it is generally understood that US has limited ability to identify MIBC in clinical practice and is sparingly used. As cystoscopy allows identification of recurrent neoplasm, concurrent biopsy, and local staging, US has not replaced the need for conventional cystoscopic surveillance for patients with NMIBC. Variant 2: Nonmuscle invasive bladder cancer with symptoms or risk factors. Post-treatment surveillance. Patients with NMIBC and risk factors require frequent surveillance for recurrent bladder cancer, which is generally done with conventional cystoscopy. In patients at intermediate risk with a history of TURBT and intravesical chemotherapy, recurrent bladder cancer is identified in up to 57% (413 of 724) of patients [8]. In patients at high risk, 59.6% (2,694 of 4,521) of patients develop multiple recurrences within 2 years of initial treatment [34].

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Post Treatment Surveillance of Bladder Cancer

In addition, progression to MIBC is seen in 8.6% to 15% of patients with high-risk disease [35-37]. CT Abdomen and Pelvis NMIBC is a heterogeneous group of tumors, and although distant metastatic disease is uncommon in this patient population, cross-sectional imaging may be used to assess for metastatic disease in patients with symptoms or risk factors. There is no relevant literature regarding the use of CT abdomen and pelvis without or with IV contrast for the evaluation of metastatic bladder cancer; however, in the absence of contraindications, IV contrast is generally indicated to improve sensitivity for the identification of metastatic disease. CT abdomen and pelvis without and with IV contrast (excluding CTU) adds little information over CT abdomen and pelvis with IV contrast and does not offer a complete examination of the urinary tract. CTU, however, is a comprehensive examination and can be used to assess for metastatic disease and metachronous upper-tract UC (see below). CT Chest Chest CT without or with IV contrast is generally not appropriate for patients with NMIBC with symptoms or risk factors, unless an abnormality is identified with chest radiography. CTU CTU is a primary imaging test for comprehensive evaluation of the genitourinary tract that can be used to identify metastatic disease and metachronous UC in patients with NMIBC who have symptoms or risk factors. Although CTU has not replaced cystoscopy, CT performs well in identifying recurrent bladder cancer following TURBT. In a study of CTU in 121 patients at risk for urothelial recurrence after TURBT (with symptoms or positive urine cytology), 59 bladder recurrences were identified in 38 patients. The authors found that overall accuracy was better in the urinary bladder during the nephrographic phase compared with the pyelographic/excretory phase (91.7% [354 of 386] versus 83.2% [321 of 386], P = . 038) [38].

Post Treatment Surveillance of Bladder Cancer. In addition, progression to MIBC is seen in 8.6% to 15% of patients with high-risk disease [35-37]. CT Abdomen and Pelvis NMIBC is a heterogeneous group of tumors, and although distant metastatic disease is uncommon in this patient population, cross-sectional imaging may be used to assess for metastatic disease in patients with symptoms or risk factors. There is no relevant literature regarding the use of CT abdomen and pelvis without or with IV contrast for the evaluation of metastatic bladder cancer; however, in the absence of contraindications, IV contrast is generally indicated to improve sensitivity for the identification of metastatic disease. CT abdomen and pelvis without and with IV contrast (excluding CTU) adds little information over CT abdomen and pelvis with IV contrast and does not offer a complete examination of the urinary tract. CTU, however, is a comprehensive examination and can be used to assess for metastatic disease and metachronous upper-tract UC (see below). CT Chest Chest CT without or with IV contrast is generally not appropriate for patients with NMIBC with symptoms or risk factors, unless an abnormality is identified with chest radiography. CTU CTU is a primary imaging test for comprehensive evaluation of the genitourinary tract that can be used to identify metastatic disease and metachronous UC in patients with NMIBC who have symptoms or risk factors. Although CTU has not replaced cystoscopy, CT performs well in identifying recurrent bladder cancer following TURBT. In a study of CTU in 121 patients at risk for urothelial recurrence after TURBT (with symptoms or positive urine cytology), 59 bladder recurrences were identified in 38 patients. The authors found that overall accuracy was better in the urinary bladder during the nephrographic phase compared with the pyelographic/excretory phase (91.7% [354 of 386] versus 83.2% [321 of 386], P = . 038) [38].

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Post Treatment Surveillance of Bladder Cancer

In another study of patients with a history of UC, CTU had a sensitivity of 77.8% (63 of 81) and specificity of 77.9% (60 of 77) for the detection of bladder cancer [39]. CTU for the evaluation of the upper urinary tract is effective in patients with symptoms, particularly in the setting of a negative cystoscopy. In a study of CTU in 121 patients at risk for urothelial recurrence after TURBT (with symptoms or positive urine cytology), 19 upper-tract recurrences were identified in 13 patients. In this study, accuracy for upper-tract recurrence was better in the nephrographic phase compared with the pyelographic phase (86.7% [260 of 300] versus 80.0% [240 of 300], P = . 028) [38]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is generally not appropriate for patients with NMIBC. The risk of metastatic disease is extremely low, FDG is excreted by the kidneys, and activity obscures evaluation of the upper and lower urinary tract for recurrent disease. MRI Abdomen and Pelvis Although distant metastatic disease is uncommon in this patient population, cross-sectional imaging may be used to assess for metastatic disease in patients with symptoms or risk factors. There is no relevant literature regarding the use of MRI abdomen and pelvis without IV contrast in the evaluation of metastatic UC. Given the improved Post-Treatment Surveillance of Bladder Cancer soft-tissue contrast of MRI compared with CT, MRI of the abdomen and pelvis without IV contrast may be acceptable for the identification of metastatic disease; however, MRI without and with IV contrast is preferred to improve sensitivity. MRU, however, is a comprehensive examination and can be used to assess for metastatic disease and metachronous upper-tract UC (see below). There has been increasing interest in using MRI for local staging of bladder cancer in the pretreatment setting. Several meta-analyses of MRI for local staging of bladder cancer have been performed.

Post Treatment Surveillance of Bladder Cancer. In another study of patients with a history of UC, CTU had a sensitivity of 77.8% (63 of 81) and specificity of 77.9% (60 of 77) for the detection of bladder cancer [39]. CTU for the evaluation of the upper urinary tract is effective in patients with symptoms, particularly in the setting of a negative cystoscopy. In a study of CTU in 121 patients at risk for urothelial recurrence after TURBT (with symptoms or positive urine cytology), 19 upper-tract recurrences were identified in 13 patients. In this study, accuracy for upper-tract recurrence was better in the nephrographic phase compared with the pyelographic phase (86.7% [260 of 300] versus 80.0% [240 of 300], P = . 028) [38]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is generally not appropriate for patients with NMIBC. The risk of metastatic disease is extremely low, FDG is excreted by the kidneys, and activity obscures evaluation of the upper and lower urinary tract for recurrent disease. MRI Abdomen and Pelvis Although distant metastatic disease is uncommon in this patient population, cross-sectional imaging may be used to assess for metastatic disease in patients with symptoms or risk factors. There is no relevant literature regarding the use of MRI abdomen and pelvis without IV contrast in the evaluation of metastatic UC. Given the improved Post-Treatment Surveillance of Bladder Cancer soft-tissue contrast of MRI compared with CT, MRI of the abdomen and pelvis without IV contrast may be acceptable for the identification of metastatic disease; however, MRI without and with IV contrast is preferred to improve sensitivity. MRU, however, is a comprehensive examination and can be used to assess for metastatic disease and metachronous upper-tract UC (see below). There has been increasing interest in using MRI for local staging of bladder cancer in the pretreatment setting. Several meta-analyses of MRI for local staging of bladder cancer have been performed.

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Post Treatment Surveillance of Bladder Cancer

For the differentiation of NMIBC from MIBC, sensitivity ranges from 97% to 92% and specificity ranges from 79% to 88% [24-26]. Vesical Imaging-Reporting and Data System (VI-RADS) using multiparametric MRI with T2-weighted imaging, DWI and dynamic contrast-enhanced imaging has been developed to identify MIBC and standardize reporting. A multireader validation study of VI-RADS for the identification of MIBC demonstrated an intraclass correlation coefficient of 0.85 among 5 readers with a pooled area under the curve of 0.90 [27]. A larger study of 340 patients (255 with NMIBC and 85 with MIBC) concluded that VI-RADS had an accuracy of 94% for identifying MIBC among 2 readers [28]. Despite these results, there are limited data for use of MRI as a screening test in patients with previously treated bladder cancer. At this time, it is generally felt that urine cytological evaluation and conventional cystoscopy are sufficiently accurate for the diagnosis of bladder recurrence in this patient population. MRU MRU offers a comprehensive evaluation of the genitourinary tract and can be used to evaluate for metastatic disease and metachronous UTUC following treatment of NMIBC. In a study of 91 examinations in 88 patients with suspected UTUC, MRU had a sensitivity of 72.4% to 86.2% and specificity of 97.9% to 99.5% for 2 readers, respectively [40]. Radiography Chest Metastatic disease in patients with NMIBC is uncommon; however, chest radiography may be appropriate in patients with NMIBC with symptoms or risk factors. Radiography Intravenous Urography CTU and, to a lesser extent, MRU have replaced IVU for the evaluation of the upper urinary tract. IVU does not have a current role in surveillance of NMIBC. US Pelvis (Bladder) In a small prospective study, transabdominal US was found to have a sensitivity of 78.6% and specificity of 100% for the diagnosis of recurrent UC of the urinary bladder, with cystoscopy as the reference standard [32].

Post Treatment Surveillance of Bladder Cancer. For the differentiation of NMIBC from MIBC, sensitivity ranges from 97% to 92% and specificity ranges from 79% to 88% [24-26]. Vesical Imaging-Reporting and Data System (VI-RADS) using multiparametric MRI with T2-weighted imaging, DWI and dynamic contrast-enhanced imaging has been developed to identify MIBC and standardize reporting. A multireader validation study of VI-RADS for the identification of MIBC demonstrated an intraclass correlation coefficient of 0.85 among 5 readers with a pooled area under the curve of 0.90 [27]. A larger study of 340 patients (255 with NMIBC and 85 with MIBC) concluded that VI-RADS had an accuracy of 94% for identifying MIBC among 2 readers [28]. Despite these results, there are limited data for use of MRI as a screening test in patients with previously treated bladder cancer. At this time, it is generally felt that urine cytological evaluation and conventional cystoscopy are sufficiently accurate for the diagnosis of bladder recurrence in this patient population. MRU MRU offers a comprehensive evaluation of the genitourinary tract and can be used to evaluate for metastatic disease and metachronous UTUC following treatment of NMIBC. In a study of 91 examinations in 88 patients with suspected UTUC, MRU had a sensitivity of 72.4% to 86.2% and specificity of 97.9% to 99.5% for 2 readers, respectively [40]. Radiography Chest Metastatic disease in patients with NMIBC is uncommon; however, chest radiography may be appropriate in patients with NMIBC with symptoms or risk factors. Radiography Intravenous Urography CTU and, to a lesser extent, MRU have replaced IVU for the evaluation of the upper urinary tract. IVU does not have a current role in surveillance of NMIBC. US Pelvis (Bladder) In a small prospective study, transabdominal US was found to have a sensitivity of 78.6% and specificity of 100% for the diagnosis of recurrent UC of the urinary bladder, with cystoscopy as the reference standard [32].

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Post Treatment Surveillance of Bladder Cancer

In this study, US accurately diagnosed bladder cancer in 78.6% (11 of 14) of patients, missing 2 tumors <3 mm and 1 lesion located in a diverticulum. In another study, the combination of grayscale US, multiplanar reconstruction, and 3-D virtual US had a sensitivity of 96.4% and specificity of 88.8% compared with conventional cystoscopy [33]. Despite these results, US has limited ability to identify MIBC or nodal metastatic disease. As cystoscopy allows identification of recurrent neoplasm, concurrent biopsy, and local staging, US has not replaced the need for cystoscopic surveillance for patients with NMIBC. Variant 3: Muscle-invasive bladder cancer with or without cystectomy. Post-treatment surveillance. Following radical cystectomy for MIBC, 5-year recurrence-free survival is approximately 58%; risk factors for recurrence include advanced tumor stage, lymph node involvement, lymphovascular invasion, high tumor grade, and positive surgical margins [10,41-43]. Recurrences can be described as pelvic relapse; surgical bed recurrence; internal and external iliac and obturator lymph node involvement or distant metastatic disease; and osseous, pulmonary, hepatic, extrapelvic lymphadenopathy, peritoneal, and brain metastases. Most recurrences occur within the first 2 years following cystectomy, and most recurrences are distant metastatic disease [44]. Pelvic relapse is seen in 34% of patients, and the 2-year risk of local failure exceeds 30% [45]. Post-Treatment Surveillance of Bladder Cancer In a study of 1,110 patients following radical cystectomy, recurrences were identified in 29.2% (324 of 1,110) of patients, and 61.7% (200 of 324) of recurrences were single-site recurrences with 43 local (22 cystectomy bed and 21 pelvic lymph node) and 138 distant (36 lung, 19 liver, 52 bone, 17 extrapelvic lymph node, 7 peritoneal, 4 brain, and 3 other) [46].

Post Treatment Surveillance of Bladder Cancer. In this study, US accurately diagnosed bladder cancer in 78.6% (11 of 14) of patients, missing 2 tumors <3 mm and 1 lesion located in a diverticulum. In another study, the combination of grayscale US, multiplanar reconstruction, and 3-D virtual US had a sensitivity of 96.4% and specificity of 88.8% compared with conventional cystoscopy [33]. Despite these results, US has limited ability to identify MIBC or nodal metastatic disease. As cystoscopy allows identification of recurrent neoplasm, concurrent biopsy, and local staging, US has not replaced the need for cystoscopic surveillance for patients with NMIBC. Variant 3: Muscle-invasive bladder cancer with or without cystectomy. Post-treatment surveillance. Following radical cystectomy for MIBC, 5-year recurrence-free survival is approximately 58%; risk factors for recurrence include advanced tumor stage, lymph node involvement, lymphovascular invasion, high tumor grade, and positive surgical margins [10,41-43]. Recurrences can be described as pelvic relapse; surgical bed recurrence; internal and external iliac and obturator lymph node involvement or distant metastatic disease; and osseous, pulmonary, hepatic, extrapelvic lymphadenopathy, peritoneal, and brain metastases. Most recurrences occur within the first 2 years following cystectomy, and most recurrences are distant metastatic disease [44]. Pelvic relapse is seen in 34% of patients, and the 2-year risk of local failure exceeds 30% [45]. Post-Treatment Surveillance of Bladder Cancer In a study of 1,110 patients following radical cystectomy, recurrences were identified in 29.2% (324 of 1,110) of patients, and 61.7% (200 of 324) of recurrences were single-site recurrences with 43 local (22 cystectomy bed and 21 pelvic lymph node) and 138 distant (36 lung, 19 liver, 52 bone, 17 extrapelvic lymph node, 7 peritoneal, 4 brain, and 3 other) [46].

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Post Treatment Surveillance of Bladder Cancer

In a smaller study of 343 patients, 46% (158) of patients developed recurrence; 30% (104) were distant, 6% (21) were distant and local, and 10% (33) were only local. Eighty-four percent of recurrences were identified within 2 years. Following cystectomy, patients are also at risk of developing UTUC, which is found in up to 3.7% of patients [47,48]. As recurrence can involve the entire urinary tract, the urethra also needs to be screened, often with urethral wash cytology, although urethral recurrence may occasionally be identified on cross- sectional imaging. The risk of urethral recurrence is 2.7% to 3.8%, and risk factors include prostatic involvement of the MIBC [47-49]. CT Abdomen and Pelvis As described earlier, recurrences can be described as pelvic relapse; surgical bed recurrence; internal and external iliac and obturator lymph node involvement or distant metastatic disease; and osseous, pulmonary, hepatic, extrapelvic lymphadenopathy, peritoneal, and brain metastases. There is no relevant literature regarding the use of CT abdomen and pelvis without or with IV contrast for the evaluation of metastatic bladder cancer; however, in the absence of contraindications, IV contrast is generally indicated to improve sensitivity for the identification of metastatic disease. CT of the abdomen and pelvis without and with IV contrast (excluding CTU) adds little over CT abdomen and pelvis with IV contrast and does not offer a complete examination of the urinary tract. CT Chest All patients with MIBC require imaging of the thorax. In the setting of bladder cancer, there is a lack of data comparing the utility of chest radiography and chest CT. Chest radiography is an effective screening examination and should be performed at regular intervals. Any abnormality identified at radiography should be followed up with a CT examination for improved characterization.

Post Treatment Surveillance of Bladder Cancer. In a smaller study of 343 patients, 46% (158) of patients developed recurrence; 30% (104) were distant, 6% (21) were distant and local, and 10% (33) were only local. Eighty-four percent of recurrences were identified within 2 years. Following cystectomy, patients are also at risk of developing UTUC, which is found in up to 3.7% of patients [47,48]. As recurrence can involve the entire urinary tract, the urethra also needs to be screened, often with urethral wash cytology, although urethral recurrence may occasionally be identified on cross- sectional imaging. The risk of urethral recurrence is 2.7% to 3.8%, and risk factors include prostatic involvement of the MIBC [47-49]. CT Abdomen and Pelvis As described earlier, recurrences can be described as pelvic relapse; surgical bed recurrence; internal and external iliac and obturator lymph node involvement or distant metastatic disease; and osseous, pulmonary, hepatic, extrapelvic lymphadenopathy, peritoneal, and brain metastases. There is no relevant literature regarding the use of CT abdomen and pelvis without or with IV contrast for the evaluation of metastatic bladder cancer; however, in the absence of contraindications, IV contrast is generally indicated to improve sensitivity for the identification of metastatic disease. CT of the abdomen and pelvis without and with IV contrast (excluding CTU) adds little over CT abdomen and pelvis with IV contrast and does not offer a complete examination of the urinary tract. CT Chest All patients with MIBC require imaging of the thorax. In the setting of bladder cancer, there is a lack of data comparing the utility of chest radiography and chest CT. Chest radiography is an effective screening examination and should be performed at regular intervals. Any abnormality identified at radiography should be followed up with a CT examination for improved characterization.

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acrac_69364_11

Post Treatment Surveillance of Bladder Cancer

There is no relevant literature regarding the use of CT chest without or with and without IV contrast in the evaluation of bladder cancer metastases to the thorax; however, CT chest is often performed as a component of the imaging follow-up of patients with MIBC. CTU CTU CTU is a primary imaging test for comprehensive evaluation of the genitourinary tract and can be used to identify distant metastatic disease and metachronous UTUC in this patient population. In one study, accuracy of CTU for UTUC was better in the nephrographic phase compared with the pyelographic phase for upper-tract recurrences (86.7% [260 of 300] versus 80.0% [240 of 300], P = . 028), although the 2 phases are complementary [38]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT in the setting of MIBC is typically used to resolve equivocal findings identified on other imaging tests, but there is increasing evidence that FDG-PET/CT alters patient management and has prognostic value compared with other staging examinations. Kibel et al [50] evaluated FDG-PET/CT prior to cystectomy for MIBC and found that FDG-PET/CT had a sensitivity of 70% (7 of 10) and specificity of 94% (30 of 32) for metastatic disease. However, occult metastatic disease was found in 7 of 42 patients with FDG-PET/CT compared with CT alone. In another study of 44 patients with MIBC, FDG-PET/CT demonstrated a sensitivity of 57% for pelvic lymph node involvement compared with 33% for CT, and FDG-PET/CT identified all bone lesions that were detected by scintigraphy [51]. A more recent study demonstrated a sensitivity of 62% to 79% for nodal metastases based on standardized uptake values [52]. A meta-analysis for nodal metastatic disease demonstrated a pooled sensitivity of 57% and specificity of 92% [53]. Given FDG activity in excreted urine, pelvic staging may be difficult. One group of authors found that with diuretics and oral hydration there was improved assessment of locally recurrent disease [54].

Post Treatment Surveillance of Bladder Cancer. There is no relevant literature regarding the use of CT chest without or with and without IV contrast in the evaluation of bladder cancer metastases to the thorax; however, CT chest is often performed as a component of the imaging follow-up of patients with MIBC. CTU CTU CTU is a primary imaging test for comprehensive evaluation of the genitourinary tract and can be used to identify distant metastatic disease and metachronous UTUC in this patient population. In one study, accuracy of CTU for UTUC was better in the nephrographic phase compared with the pyelographic phase for upper-tract recurrences (86.7% [260 of 300] versus 80.0% [240 of 300], P = . 028), although the 2 phases are complementary [38]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT in the setting of MIBC is typically used to resolve equivocal findings identified on other imaging tests, but there is increasing evidence that FDG-PET/CT alters patient management and has prognostic value compared with other staging examinations. Kibel et al [50] evaluated FDG-PET/CT prior to cystectomy for MIBC and found that FDG-PET/CT had a sensitivity of 70% (7 of 10) and specificity of 94% (30 of 32) for metastatic disease. However, occult metastatic disease was found in 7 of 42 patients with FDG-PET/CT compared with CT alone. In another study of 44 patients with MIBC, FDG-PET/CT demonstrated a sensitivity of 57% for pelvic lymph node involvement compared with 33% for CT, and FDG-PET/CT identified all bone lesions that were detected by scintigraphy [51]. A more recent study demonstrated a sensitivity of 62% to 79% for nodal metastases based on standardized uptake values [52]. A meta-analysis for nodal metastatic disease demonstrated a pooled sensitivity of 57% and specificity of 92% [53]. Given FDG activity in excreted urine, pelvic staging may be difficult. One group of authors found that with diuretics and oral hydration there was improved assessment of locally recurrent disease [54].

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Post Treatment Surveillance of Bladder Cancer

In a study that included 41 patients with suspected recurrent bladder cancer after primary treatment that underwent FDG-PET/CT, authors found that FDG-PET/CT had a sensitivity of 87% and specificity of 94% for recurrent/metastatic bladder cancer following treatment [55]. In this study, metastatic disease was found in abdominal and pelvic lymph nodes, including suprarenal lymph nodes; pulmonary and osseous metastatic disease was also identified. Perhaps more importantly, the results of the FDG-PET/CT changed the treatment decision in 40% of patients and had prognostic value in determining overall survival and progression-free survival. In another study of the National Oncologic PET Registry, authors found that FDG-PET/CT changed management in approximately 35% of patients and had a large impact on chemotherapy monitoring [56]. In addition, there is Post-Treatment Surveillance of Bladder Cancer increasing evidence that FDG-PET/CT can be used to assess for treatment response after neoadjuvant or induction chemotherapy [57-59]. Although not widely available, there is increasing interest in 11C-choline-PET. In a study of 27 patients with either MIBC or recurrent NMIBC that failed TURBT and intravesical therapy, the presence of residual bladder cancer was detected in 84% (21 of 25) of patients with CT and 96% (24 of 25) of patients with 11C-choline PET, and lymph node involvement was identified correctly in 50% (4 of 8) of patients with CT and 62% (5 of 8) of patients with PET [60]. Fluoroscopy Abdomen Loopogram Abdominal radiography can be useful in the early postoperative setting to evaluate for ureteral stent location and to evaluate patients with abdominal distention and postoperative ileus.

Post Treatment Surveillance of Bladder Cancer. In a study that included 41 patients with suspected recurrent bladder cancer after primary treatment that underwent FDG-PET/CT, authors found that FDG-PET/CT had a sensitivity of 87% and specificity of 94% for recurrent/metastatic bladder cancer following treatment [55]. In this study, metastatic disease was found in abdominal and pelvic lymph nodes, including suprarenal lymph nodes; pulmonary and osseous metastatic disease was also identified. Perhaps more importantly, the results of the FDG-PET/CT changed the treatment decision in 40% of patients and had prognostic value in determining overall survival and progression-free survival. In another study of the National Oncologic PET Registry, authors found that FDG-PET/CT changed management in approximately 35% of patients and had a large impact on chemotherapy monitoring [56]. In addition, there is Post-Treatment Surveillance of Bladder Cancer increasing evidence that FDG-PET/CT can be used to assess for treatment response after neoadjuvant or induction chemotherapy [57-59]. Although not widely available, there is increasing interest in 11C-choline-PET. In a study of 27 patients with either MIBC or recurrent NMIBC that failed TURBT and intravesical therapy, the presence of residual bladder cancer was detected in 84% (21 of 25) of patients with CT and 96% (24 of 25) of patients with 11C-choline PET, and lymph node involvement was identified correctly in 50% (4 of 8) of patients with CT and 62% (5 of 8) of patients with PET [60]. Fluoroscopy Abdomen Loopogram Abdominal radiography can be useful in the early postoperative setting to evaluate for ureteral stent location and to evaluate patients with abdominal distention and postoperative ileus.

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Post Treatment Surveillance of Bladder Cancer

A fluoroscopic loopogram, in which water- soluble contrast is instilled into an ileal conduit in a retrograde fashion, can be used to evaluate for leak in the early postoperative period and to confirm patent ureteral anastomoses in the setting of hydronephrosis and declining renal function following urinary diversion. Abdominal radiography and fluoroscopic examinations are not useful for detection of tumor recurrence. MRI Abdomen and Pelvis MRI performs well for identifying metastatic disease within the abdomen and pelvis; however, nodal disease is largely based on size criteria. A recent meta-analysis evaluating nodal metastatic disease in the setting of bladder or prostate cancer demonstrated a pooled per-patient sensitivity of 56% and specificity of 94% [61]. There is no relevant literature regarding the use of MRI of the abdomen and pelvis without IV contrast in the evaluation of metastatic UC. Given the improved soft-tissue contrast of MRI compared with CT, MRI of the abdomen and pelvis without IV contrast may be acceptable for the identification of metastatic disease; however, MRI without and with IV contrast is preferred to improve sensitivity. Although MRI can be used for local staging of bladder cancer, the presence of inflammation and fibrosis affects the accuracy of MRI following neoadjuvant chemoradiation, when accuracy drops to only 30% [62]. However, DWI may help distinguish inflammation and fibrosis from tumor; in a small study of 20 patients who underwent low- dose neoadjuvant chemoradiation, MRI had an accuracy rate of 44% in determining pathologic response for T2- weighted imaging alone, 33% for dynamic contrast-enhanced imaging, and 80% for DWI [63]. MRU MRU is a primary imaging test for the comprehensive evaluation of the genitourinary tract and can be used to assess for metastatic disease and metachronous UTUC.

Post Treatment Surveillance of Bladder Cancer. A fluoroscopic loopogram, in which water- soluble contrast is instilled into an ileal conduit in a retrograde fashion, can be used to evaluate for leak in the early postoperative period and to confirm patent ureteral anastomoses in the setting of hydronephrosis and declining renal function following urinary diversion. Abdominal radiography and fluoroscopic examinations are not useful for detection of tumor recurrence. MRI Abdomen and Pelvis MRI performs well for identifying metastatic disease within the abdomen and pelvis; however, nodal disease is largely based on size criteria. A recent meta-analysis evaluating nodal metastatic disease in the setting of bladder or prostate cancer demonstrated a pooled per-patient sensitivity of 56% and specificity of 94% [61]. There is no relevant literature regarding the use of MRI of the abdomen and pelvis without IV contrast in the evaluation of metastatic UC. Given the improved soft-tissue contrast of MRI compared with CT, MRI of the abdomen and pelvis without IV contrast may be acceptable for the identification of metastatic disease; however, MRI without and with IV contrast is preferred to improve sensitivity. Although MRI can be used for local staging of bladder cancer, the presence of inflammation and fibrosis affects the accuracy of MRI following neoadjuvant chemoradiation, when accuracy drops to only 30% [62]. However, DWI may help distinguish inflammation and fibrosis from tumor; in a small study of 20 patients who underwent low- dose neoadjuvant chemoradiation, MRI had an accuracy rate of 44% in determining pathologic response for T2- weighted imaging alone, 33% for dynamic contrast-enhanced imaging, and 80% for DWI [63]. MRU MRU is a primary imaging test for the comprehensive evaluation of the genitourinary tract and can be used to assess for metastatic disease and metachronous UTUC.

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acrac_69364_14

Post Treatment Surveillance of Bladder Cancer

In a study of 91 examinations in 88 patients with suspected UTUC, MRU had a sensitivity of 72.4% to 86.2% and specificity of 97.9% to 99.5% for UTUC for 2 readers, respectively [40]. Radiography Chest All patients with MIBC require imaging of the thorax. Chest radiographs are an effective screening examination and should be performed at regular intervals. Any abnormality identified on radiography should be followed with a CT examination for improved characterization. Radiography Intravenous Urography CTU and, to a lesser extent, MRU have replaced IVU for the evaluation of the upper urinary tract. In a study of 128 patients at high risk for UTUC, in whom 46 patients were diagnosed with UTUC, excretory urography had a per- patient sensitivity of 80.4% (37 of 46) and a specificity of 81.0% (47 of 58), whereas CTU had a sensitivity of 93.5% (43 of 46) and a specificity of 94.8% (55 of 58) [64]. IVU is not recommended for detection of tumor recurrence. However, IVU could be used to assess for ureteral anastomotic patency if reflux cannot be demonstrated on a loopogram. US Pelvis (Bladder) Following cystectomy, the acoustic window is limited, and US is of little clinical use for the identification of local recurrence or nodal metastatic disease. Given the high incidence of recurrent disease (up to 46% of patients) following cystectomy for MIBC, surveillance imaging with CT or MRI is recommended [43]. US may be useful to assess the kidneys for hydronephrosis in the setting of declining renal function, regardless of whether the urinary bladder has been resected or not. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www. acr.org/ac.

Post Treatment Surveillance of Bladder Cancer. In a study of 91 examinations in 88 patients with suspected UTUC, MRU had a sensitivity of 72.4% to 86.2% and specificity of 97.9% to 99.5% for UTUC for 2 readers, respectively [40]. Radiography Chest All patients with MIBC require imaging of the thorax. Chest radiographs are an effective screening examination and should be performed at regular intervals. Any abnormality identified on radiography should be followed with a CT examination for improved characterization. Radiography Intravenous Urography CTU and, to a lesser extent, MRU have replaced IVU for the evaluation of the upper urinary tract. In a study of 128 patients at high risk for UTUC, in whom 46 patients were diagnosed with UTUC, excretory urography had a per- patient sensitivity of 80.4% (37 of 46) and a specificity of 81.0% (47 of 58), whereas CTU had a sensitivity of 93.5% (43 of 46) and a specificity of 94.8% (55 of 58) [64]. IVU is not recommended for detection of tumor recurrence. However, IVU could be used to assess for ureteral anastomotic patency if reflux cannot be demonstrated on a loopogram. US Pelvis (Bladder) Following cystectomy, the acoustic window is limited, and US is of little clinical use for the identification of local recurrence or nodal metastatic disease. Given the high incidence of recurrent disease (up to 46% of patients) following cystectomy for MIBC, surveillance imaging with CT or MRI is recommended [43]. US may be useful to assess the kidneys for hydronephrosis in the setting of declining renal function, regardless of whether the urinary bladder has been resected or not. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www. acr.org/ac.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Introduction/Background Soft tissue vascular anomalies (VAs) may be diagnosed prenatally or at any time during life [1-3]. Anomalies of the soft tissues may be located in the extremities, face, scalp, neck, airway, thoracoabdominal wall, mediastinum, lungs, and abdomen (mesentery, retroperitoneum, and viscera). They may be associated with syndromes and may signal the presence of internal vascular lesions. Soft tissue VAs are subdivided into broad categories of vascular malformations (VMs) and vascular tumors (VTs). VTs are true neoplasms with increased mitotic activity and endothelial cell turnover; VMs are composed of abnormal or defective formation of vascular tissue [4] (see Appendix 1). The prevalence of VMs varies by type: venous malformations (70%), lymphatic malformations (12%), arteriovenous malformations (AVMs) (8%), combined malformation syndromes (6%), and capillary malformations (4%) [5]. They may be divided into simple (further divided into low-flow or fast-flow VMs) or combined. Low- flow, simple VMs often contain 1 type of low-flow vessel: capillary, lymphatic, or venous vessel. AVMs or arteriovenous fistulas (AVFs) are fast-flow, simple VMs. Combined VMs are composed of more than 2 types of simple VM components and may be named for a major vessel [4,6]. Complex anomalies may be associated with overgrowth syndromes, which are often composed of infiltrative venous and lymphatic tissues through thickened subcutaneous fat affecting the trunk and/or limbs [7-10] (see Appendix 2). VTs are divided into masses that behave in a benign, locally aggressive, borderline, or malignant manner. The most common benign VT is infantile hemangioma, which presents in the newborn period, whereas other VTs, malignant and other aggressive vascular lesions, may be diagnosed at any age. Most benign lesions are observed or treated in a noninvasive manner.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Introduction/Background Soft tissue vascular anomalies (VAs) may be diagnosed prenatally or at any time during life [1-3]. Anomalies of the soft tissues may be located in the extremities, face, scalp, neck, airway, thoracoabdominal wall, mediastinum, lungs, and abdomen (mesentery, retroperitoneum, and viscera). They may be associated with syndromes and may signal the presence of internal vascular lesions. Soft tissue VAs are subdivided into broad categories of vascular malformations (VMs) and vascular tumors (VTs). VTs are true neoplasms with increased mitotic activity and endothelial cell turnover; VMs are composed of abnormal or defective formation of vascular tissue [4] (see Appendix 1). The prevalence of VMs varies by type: venous malformations (70%), lymphatic malformations (12%), arteriovenous malformations (AVMs) (8%), combined malformation syndromes (6%), and capillary malformations (4%) [5]. They may be divided into simple (further divided into low-flow or fast-flow VMs) or combined. Low- flow, simple VMs often contain 1 type of low-flow vessel: capillary, lymphatic, or venous vessel. AVMs or arteriovenous fistulas (AVFs) are fast-flow, simple VMs. Combined VMs are composed of more than 2 types of simple VM components and may be named for a major vessel [4,6]. Complex anomalies may be associated with overgrowth syndromes, which are often composed of infiltrative venous and lymphatic tissues through thickened subcutaneous fat affecting the trunk and/or limbs [7-10] (see Appendix 2). VTs are divided into masses that behave in a benign, locally aggressive, borderline, or malignant manner. The most common benign VT is infantile hemangioma, which presents in the newborn period, whereas other VTs, malignant and other aggressive vascular lesions, may be diagnosed at any age. Most benign lesions are observed or treated in a noninvasive manner.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Locally aggressive and borderline VTs present shortly after birth and may present with thrombocytopenia and/or a consumptive coagulopathy, which can complicate treatment. Malignant VTs are rapidly growing masses found in children of all ages, are often more aggressive than similar tumors in adults, and may be difficult to accurately diagnose due to poorly differentiated cell type [4,6]. Initial Imaging Definition Initial imaging is defined as imaging at the beginning of the care episode for the medical condition defined by the variant. More than one procedure can be considered usually appropriate in the initial imaging evaluation when: The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] OR Discussion of Procedures by Variant Variant 1: Infant. Clinical signs or symptoms of infantile hemangioma. Initial imaging. Infantile hemangiomas are the most common benign neoplasm of infancy, with a prevalence of 4% to 5% [13]. Infantile hemangiomas, distinct from VMs, are a true neoplasm rather than an abnormality of embryonic development of vascular tissue (see Appendix 1). They become clinically evident within the first few weeks of life and progress through phases of latency, growth, and plateau, predictably by the first year of life; in rare cases, growth continues through 24 months of age. With either complete or partial involution, lesion regression is completed by 4 years of age in 90% of cases but may continue through to 8 years of age [13,14].

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Locally aggressive and borderline VTs present shortly after birth and may present with thrombocytopenia and/or a consumptive coagulopathy, which can complicate treatment. Malignant VTs are rapidly growing masses found in children of all ages, are often more aggressive than similar tumors in adults, and may be difficult to accurately diagnose due to poorly differentiated cell type [4,6]. Initial Imaging Definition Initial imaging is defined as imaging at the beginning of the care episode for the medical condition defined by the variant. More than one procedure can be considered usually appropriate in the initial imaging evaluation when: The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] OR Discussion of Procedures by Variant Variant 1: Infant. Clinical signs or symptoms of infantile hemangioma. Initial imaging. Infantile hemangiomas are the most common benign neoplasm of infancy, with a prevalence of 4% to 5% [13]. Infantile hemangiomas, distinct from VMs, are a true neoplasm rather than an abnormality of embryonic development of vascular tissue (see Appendix 1). They become clinically evident within the first few weeks of life and progress through phases of latency, growth, and plateau, predictably by the first year of life; in rare cases, growth continues through 24 months of age. With either complete or partial involution, lesion regression is completed by 4 years of age in 90% of cases but may continue through to 8 years of age [13,14].

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Risk factors for having infantile hemangiomas include prematurity, White race (3%-10%), and female sex (female:male ratio range 1.4:1 to 3:1) [15]. A rare, but important, location of infantile hemangiomas is in the airway, because rapid proliferation of the VT can obstruct the airway. Infantile hemangiomas of the airway are most commonly localized in the subglottic airway but may be more diffuse, in a beard-like distribution throughout the soft tissues overlying the mandible and neck [18]. Subglottic infantile hemangiomas may also extend from the neck into the mediastinum. Infantile hemangioma may also be associated with VAs of other organs. PHACE, an acronym for posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, and eye abnormalities, is predominantly a neurovascular malformation syndrome [19]. Imaging of the non-CNS lesions in PHACE syndrome, although not specifically addressed, are included in the recommendations of Variant 1. Imaging recommendations of hepatic hemangiomas found in patients with multiple cutaneous infantile hemangiomas are presented in Variant 2. Arteriography Area of Interest There is no relevant literature to support the use of arteriography of the area of interest as the initial imaging modality in infants with infantile hemangiomas. CT Area of Interest With IV Contrast When optimal imaging of the airway is required, as with hemangiomas involving the supra- or infraglottic airway or when in a beard-like distribution over the face and neck, CT with intravenous (IV) contrast may be useful. In a study of 11 children with hemangiomas of the upper airway who underwent CT, Koplewitz et al [20] found CT to have an improved definition of the airway lesion, presence, localization, and complete extent of the lesion and a more accurate size assessment compared with bronchoscopy.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Risk factors for having infantile hemangiomas include prematurity, White race (3%-10%), and female sex (female:male ratio range 1.4:1 to 3:1) [15]. A rare, but important, location of infantile hemangiomas is in the airway, because rapid proliferation of the VT can obstruct the airway. Infantile hemangiomas of the airway are most commonly localized in the subglottic airway but may be more diffuse, in a beard-like distribution throughout the soft tissues overlying the mandible and neck [18]. Subglottic infantile hemangiomas may also extend from the neck into the mediastinum. Infantile hemangioma may also be associated with VAs of other organs. PHACE, an acronym for posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, and eye abnormalities, is predominantly a neurovascular malformation syndrome [19]. Imaging of the non-CNS lesions in PHACE syndrome, although not specifically addressed, are included in the recommendations of Variant 1. Imaging recommendations of hepatic hemangiomas found in patients with multiple cutaneous infantile hemangiomas are presented in Variant 2. Arteriography Area of Interest There is no relevant literature to support the use of arteriography of the area of interest as the initial imaging modality in infants with infantile hemangiomas. CT Area of Interest With IV Contrast When optimal imaging of the airway is required, as with hemangiomas involving the supra- or infraglottic airway or when in a beard-like distribution over the face and neck, CT with intravenous (IV) contrast may be useful. In a study of 11 children with hemangiomas of the upper airway who underwent CT, Koplewitz et al [20] found CT to have an improved definition of the airway lesion, presence, localization, and complete extent of the lesion and a more accurate size assessment compared with bronchoscopy.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT area of interest without and with IV contrast as the initial imaging modality in infants with infantile hemangiomas. In the study by Koplewitz et al [20], noncontrast and contrast-enhanced CT scans were performed. It was found that the lesions appeared larger after IV contrast was given and that the complete extent and localization of the lesion could be best defined. Soft Tissue Vascular Anomalies-Child CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT area of interest without IV contrast as the initial imaging modality in infants with infantile hemangiomas. CTA and CTV Area of Interest With IV Contrast There is no relevant literature to support the use of CT angiography (CTA) or CT venography (CTV) area of interest with IV contrast as the initial imaging modality in infants with infantile hemangiomas. MRA and MRV Area of Interest Without and With IV Contrast Dynamic MR angiography (MRA) and MR venography (MRV) with IV contrast of untreated infantile hemangiomas is capable of showing supplying arterial and draining venous vessels [15]. MRI Area of Interest Without and With IV Contrast MRI of the area of interest without and with IV contrast in patients with infantile hemangiomas may be useful when clinically determining the complete extent of the lesion is not possible, such as when the infantile hemangiomas of the face and deep facial structures or periorbital and intraorbital extent must be defined, when lumbosacral region infantile hemangiomas are present and underlying tethering or other spinal cord anomaly may be present, and there are beard-type infantile hemangiomas that occupy the pharyngeal region and may affect the oropharyngeal airway.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT area of interest without and with IV contrast as the initial imaging modality in infants with infantile hemangiomas. In the study by Koplewitz et al [20], noncontrast and contrast-enhanced CT scans were performed. It was found that the lesions appeared larger after IV contrast was given and that the complete extent and localization of the lesion could be best defined. Soft Tissue Vascular Anomalies-Child CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT area of interest without IV contrast as the initial imaging modality in infants with infantile hemangiomas. CTA and CTV Area of Interest With IV Contrast There is no relevant literature to support the use of CT angiography (CTA) or CT venography (CTV) area of interest with IV contrast as the initial imaging modality in infants with infantile hemangiomas. MRA and MRV Area of Interest Without and With IV Contrast Dynamic MR angiography (MRA) and MR venography (MRV) with IV contrast of untreated infantile hemangiomas is capable of showing supplying arterial and draining venous vessels [15]. MRI Area of Interest Without and With IV Contrast MRI of the area of interest without and with IV contrast in patients with infantile hemangiomas may be useful when clinically determining the complete extent of the lesion is not possible, such as when the infantile hemangiomas of the face and deep facial structures or periorbital and intraorbital extent must be defined, when lumbosacral region infantile hemangiomas are present and underlying tethering or other spinal cord anomaly may be present, and there are beard-type infantile hemangiomas that occupy the pharyngeal region and may affect the oropharyngeal airway.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

MRI may also be useful in patients with infantile hemangiomas in anatomic locations, when the presence or growth of the lesion may be disfiguring or interfere with sight or hearing, the face, airway, ears, or breast [17]. MRI Area of Interest Without IV Contrast There is no relevant literature to support the use of MRI of the area of interest without IV contrast as the initial imaging modality for infants with infantile hemangiomas. Radiography Area of Interest There is no relevant literature to support the use of radiography area of interest as the initial imaging modality in infants with infantile hemangiomas. US Area of Interest Ultrasound (US) of the area of interest is useful to distinguish imaging features of infantile hemangiomas from VMs. Paltiel et al [21] studied 49 lesions and Ding et al [14] studied 66 lesions, describing US imaging characteristics of superficial and deep infantile hemangiomas from well-circumscribed mixed echogenicity solid masses with central and peripheral vessels on grayscale US. Both groups showed that US is useful in distinguishing infantile hemangiomas from VMs and for identifying infantile hemangiomas, which may be combined with other VA components [14,21]. US Area of Interest With IV Contrast There is no relevant literature to support the use of US area of interest with IV contrast as the initial imaging modality in infants with infantile hemangiomas. US Duplex Doppler Area of Interest US with duplex Doppler is most useful to assess and confirm diagnosis of infantile hemangiomas. Paltiel et al [21] studied 49 lesions and Ding et al [14] studied 66 lesions, showing that a combination of arterial and venous waveforms on US duplex Doppler enables distinguishing infantile hemangiomas from low-flow VMs.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. MRI may also be useful in patients with infantile hemangiomas in anatomic locations, when the presence or growth of the lesion may be disfiguring or interfere with sight or hearing, the face, airway, ears, or breast [17]. MRI Area of Interest Without IV Contrast There is no relevant literature to support the use of MRI of the area of interest without IV contrast as the initial imaging modality for infants with infantile hemangiomas. Radiography Area of Interest There is no relevant literature to support the use of radiography area of interest as the initial imaging modality in infants with infantile hemangiomas. US Area of Interest Ultrasound (US) of the area of interest is useful to distinguish imaging features of infantile hemangiomas from VMs. Paltiel et al [21] studied 49 lesions and Ding et al [14] studied 66 lesions, describing US imaging characteristics of superficial and deep infantile hemangiomas from well-circumscribed mixed echogenicity solid masses with central and peripheral vessels on grayscale US. Both groups showed that US is useful in distinguishing infantile hemangiomas from VMs and for identifying infantile hemangiomas, which may be combined with other VA components [14,21]. US Area of Interest With IV Contrast There is no relevant literature to support the use of US area of interest with IV contrast as the initial imaging modality in infants with infantile hemangiomas. US Duplex Doppler Area of Interest US with duplex Doppler is most useful to assess and confirm diagnosis of infantile hemangiomas. Paltiel et al [21] studied 49 lesions and Ding et al [14] studied 66 lesions, showing that a combination of arterial and venous waveforms on US duplex Doppler enables distinguishing infantile hemangiomas from low-flow VMs.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

A multicenter prospective study of 1,656 infants with infantile hemangiomas confirmed that patients with higher numbers of cutaneous infantile hemangiomas have a greater incidence of infantile hepatic hemangioma, 8.3% in patients with 5 to 9 lesions compared with 0.4% in patients with <5 cutaneous lesions. Based on the results of this study, screening liver imaging examination is indicated in patients with 5 cutaneous infantile hemangiomas and for patients up to 9 months of age [23]. Soft Tissue Vascular Anomalies-Child In an analysis of 121 children with hepatic hemangioma in the Liver Hemangioma Registry, Kulungowski et al [24] found that 88 children had multiple cutaneous infantile hemangiomas lesions, 68 (77%) of which were multifocal and 20 (23%) of which were diffuse type infantile hepatic hemangioma. Arteriography Abdomen There is no relevant literature to support the use of arteriography of the abdomen as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. CT Abdomen With IV Contrast There is no relevant literature to support the use of CT of the abdomen with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. CT Abdomen Without and With IV Contrast There is no relevant literature to support the use of CT of the abdomen without and with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. CT Abdomen Without IV Contrast There is no relevant literature to support the use of CT of the abdomen without IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. A multicenter prospective study of 1,656 infants with infantile hemangiomas confirmed that patients with higher numbers of cutaneous infantile hemangiomas have a greater incidence of infantile hepatic hemangioma, 8.3% in patients with 5 to 9 lesions compared with 0.4% in patients with <5 cutaneous lesions. Based on the results of this study, screening liver imaging examination is indicated in patients with 5 cutaneous infantile hemangiomas and for patients up to 9 months of age [23]. Soft Tissue Vascular Anomalies-Child In an analysis of 121 children with hepatic hemangioma in the Liver Hemangioma Registry, Kulungowski et al [24] found that 88 children had multiple cutaneous infantile hemangiomas lesions, 68 (77%) of which were multifocal and 20 (23%) of which were diffuse type infantile hepatic hemangioma. Arteriography Abdomen There is no relevant literature to support the use of arteriography of the abdomen as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. CT Abdomen With IV Contrast There is no relevant literature to support the use of CT of the abdomen with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. CT Abdomen Without and With IV Contrast There is no relevant literature to support the use of CT of the abdomen without and with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. CT Abdomen Without IV Contrast There is no relevant literature to support the use of CT of the abdomen without IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

CTA and CTV Abdomen With IV Contrast There is no relevant literature to support the use of CTA and CTV of the abdomen with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. MRA and MRV Abdomen Without and With IV Contrast There is no relevant literature to support the use of MRA and MRV of the abdomen without and with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. MRI Abdomen Without and With IV Contrast There is no relevant literature to support the use of MRI of the abdomen without and with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. A recent guidance document of the American Society of Pediatric Hematology Oncology Vascular Anomalies Special Interest Group recommends contrast-enhanced MRI of the liver including dynamic sequences if the diagnosis is unclear following Doppler US [25]. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI of the abdomen and pelvis without IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. Radiography Abdomen There is no relevant literature to support the use of radiography of the abdomen as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. CTA and CTV Abdomen With IV Contrast There is no relevant literature to support the use of CTA and CTV of the abdomen with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. MRA and MRV Abdomen Without and With IV Contrast There is no relevant literature to support the use of MRA and MRV of the abdomen without and with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. MRI Abdomen Without and With IV Contrast There is no relevant literature to support the use of MRI of the abdomen without and with IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. A recent guidance document of the American Society of Pediatric Hematology Oncology Vascular Anomalies Special Interest Group recommends contrast-enhanced MRI of the liver including dynamic sequences if the diagnosis is unclear following Doppler US [25]. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI of the abdomen and pelvis without IV contrast as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. Radiography Abdomen There is no relevant literature to support the use of radiography of the abdomen as the initial imaging modality when screening for hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas.

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acrac_3186695_7

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

US Abdomen With IV Contrast US of the abdomen with IV contrast, specifically for evaluation of the liver, for the presence of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas may be used to increase the sensitivity and diagnostic confidence, particularly for focal lesions that are seen in congenital hepatic hemangiomas rather than the diffuse and multifocal hepatic hemangiomas seen in infantile hemangiomas [26,27]. The addition of IV contrast for Soft Tissue Vascular Anomalies-Child US of the abdomen has been shown by El-Ali et al [27] to differentiate infantile hepatic hemangioma in infants from congenital hemangioma of the liver in 5 infants based on the pattern of early and late arterial phase and delayed washout of IV contrast (P = . 0016). The IV contrast enhancement pattern on US was similar to the manner in which the lesions are known to enhance with IV contrast on CT and MRI examinations [28]. US Duplex Doppler Abdomen A recent guidance document of the American Society of Pediatric Hematology Oncology Vascular Anomalies Special Interest Group recommends Doppler US of the liver as the preferred initial imaging study. On US examination imaging features such as multifocal and diffuse patterns are more specific to infantile hepatic hemangiomas and may be used to help differentiate them from congenital hemangiomas of the liver [25]. Solitary lesions may be larger in diameter and of heterogeneous echogenicity, with more prominent peripheral vascular components [26]. Variant 3: Child. Clinical signs or symptoms of vascular anomaly (tumor or malformation) not suggesting infantile hemangioma. Initial imaging. VAs are a diverse group of lesions including tumors with benign, locally aggressive, or malignant behaviors and malformations, which may involve low-flow (venous or lymphatic) or fast-flow (arterial) blood flow [4] (see Appendix 1).

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. US Abdomen With IV Contrast US of the abdomen with IV contrast, specifically for evaluation of the liver, for the presence of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas may be used to increase the sensitivity and diagnostic confidence, particularly for focal lesions that are seen in congenital hepatic hemangiomas rather than the diffuse and multifocal hepatic hemangiomas seen in infantile hemangiomas [26,27]. The addition of IV contrast for Soft Tissue Vascular Anomalies-Child US of the abdomen has been shown by El-Ali et al [27] to differentiate infantile hepatic hemangioma in infants from congenital hemangioma of the liver in 5 infants based on the pattern of early and late arterial phase and delayed washout of IV contrast (P = . 0016). The IV contrast enhancement pattern on US was similar to the manner in which the lesions are known to enhance with IV contrast on CT and MRI examinations [28]. US Duplex Doppler Abdomen A recent guidance document of the American Society of Pediatric Hematology Oncology Vascular Anomalies Special Interest Group recommends Doppler US of the liver as the preferred initial imaging study. On US examination imaging features such as multifocal and diffuse patterns are more specific to infantile hepatic hemangiomas and may be used to help differentiate them from congenital hemangiomas of the liver [25]. Solitary lesions may be larger in diameter and of heterogeneous echogenicity, with more prominent peripheral vascular components [26]. Variant 3: Child. Clinical signs or symptoms of vascular anomaly (tumor or malformation) not suggesting infantile hemangioma. Initial imaging. VAs are a diverse group of lesions including tumors with benign, locally aggressive, or malignant behaviors and malformations, which may involve low-flow (venous or lymphatic) or fast-flow (arterial) blood flow [4] (see Appendix 1).

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Many VAs are fully formed before birth and do not clinically present in a fashion typical of infantile hemangiomas. Imaging characterization of the lesion and delineation of its extent are warranted. Arteriography Area of Interest There is no relevant literature to support the use of arteriography area of interest as the initial imaging modality for vascular lesion such as tumor or malformation. CT Area of Interest With IV Contrast There is no relevant literature to support the use of CT area of interest with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT area of interest without and with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT area of interest without IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. CTA and CTV Area of Interest With IV Contrast There is no relevant literature to support the use of CTA and CTV area of interest with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. MRA and MRV Area of Interest Without and With IV Contrast Using contrast-enhanced MRA and MRV patterns of high or low signal intensity can help distinguish between low- flow and fast-flow VMs. In a study by van Rijswijk et al [29], they describe a 95% specificity and 83% sensitivity in differentiating venous and nonvenous malformations using dynamic contrast-enhanced MRA. Dynamic 4-D MRA with IV contrast may be used to detect the presence of arteriovenous microshunts in VMs, which have been found to be associated with the presence of phleboliths [30].

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Many VAs are fully formed before birth and do not clinically present in a fashion typical of infantile hemangiomas. Imaging characterization of the lesion and delineation of its extent are warranted. Arteriography Area of Interest There is no relevant literature to support the use of arteriography area of interest as the initial imaging modality for vascular lesion such as tumor or malformation. CT Area of Interest With IV Contrast There is no relevant literature to support the use of CT area of interest with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT area of interest without and with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT area of interest without IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. CTA and CTV Area of Interest With IV Contrast There is no relevant literature to support the use of CTA and CTV area of interest with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation. MRA and MRV Area of Interest Without and With IV Contrast Using contrast-enhanced MRA and MRV patterns of high or low signal intensity can help distinguish between low- flow and fast-flow VMs. In a study by van Rijswijk et al [29], they describe a 95% specificity and 83% sensitivity in differentiating venous and nonvenous malformations using dynamic contrast-enhanced MRA. Dynamic 4-D MRA with IV contrast may be used to detect the presence of arteriovenous microshunts in VMs, which have been found to be associated with the presence of phleboliths [30].

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Subtraction MRA techniques subtract MR signal from noncontrast-enhanced MR images from a contrast-enhanced MRA, resulting in improved visualization of vascular structures as soft tissue signal is removed [31]. There may also be value in the use of noncontrast MRA as an anatomic survey before performing contrast-enhanced MRA to facilitate planning of field of view and contrast bolus timing [32]. MRA Area of Interest Without IV Contrast Numerous noncontrast-enhanced MRA sequences are also available, relying on the speed of blood flow (flow- dependent) and subject to signal loss in vessels with slow blood flow. Flow-independent noncontrast-enhanced MRA sequences produce bright blood or dark blood pool images and enable imaging a larger field of view. Noncontrast MRA images may incorporate longer scan times and therefore produce higher spatial resolution images Soft Tissue Vascular Anomalies-Child [33]. Noncontrast MRA does not provide dynamic flow information provided by contrast-enhanced MRA. Furthermore, although time-of-flight cannot be used to characterize soft tissue components, it does show the feeding and draining vessels of a fast-flow VM [34]. MRI Area of Interest Without and With IV Contrast MRI area of interest without and with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation may be helpful as the initial imaging examination and may be performed contemporaneously with US to investigate a soft tissue mass or skin discoloration. MRI findings typically show a lobulated and often infiltrative soft tissue mass with T1 hypointense and T2 hyperintense signal, variable vascular flow voids, variable patterns of enhancement, and possibly phleboliths, depending upon the type of lesion. The addition of MRA may be beneficial to making a definitive diagnosis [31].

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Subtraction MRA techniques subtract MR signal from noncontrast-enhanced MR images from a contrast-enhanced MRA, resulting in improved visualization of vascular structures as soft tissue signal is removed [31]. There may also be value in the use of noncontrast MRA as an anatomic survey before performing contrast-enhanced MRA to facilitate planning of field of view and contrast bolus timing [32]. MRA Area of Interest Without IV Contrast Numerous noncontrast-enhanced MRA sequences are also available, relying on the speed of blood flow (flow- dependent) and subject to signal loss in vessels with slow blood flow. Flow-independent noncontrast-enhanced MRA sequences produce bright blood or dark blood pool images and enable imaging a larger field of view. Noncontrast MRA images may incorporate longer scan times and therefore produce higher spatial resolution images Soft Tissue Vascular Anomalies-Child [33]. Noncontrast MRA does not provide dynamic flow information provided by contrast-enhanced MRA. Furthermore, although time-of-flight cannot be used to characterize soft tissue components, it does show the feeding and draining vessels of a fast-flow VM [34]. MRI Area of Interest Without and With IV Contrast MRI area of interest without and with IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation may be helpful as the initial imaging examination and may be performed contemporaneously with US to investigate a soft tissue mass or skin discoloration. MRI findings typically show a lobulated and often infiltrative soft tissue mass with T1 hypointense and T2 hyperintense signal, variable vascular flow voids, variable patterns of enhancement, and possibly phleboliths, depending upon the type of lesion. The addition of MRA may be beneficial to making a definitive diagnosis [31].

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

MRI Area of Interest Without IV Contrast MRI area of interest without IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation may be helpful as the initial imaging examination and may be performed contemporaneously with US to investigate a soft tissue mass or skin discoloration. MRI without IV contrast typically shows a lobulated and often infiltrative soft tissue mass with T1 hypointense and T2 hyperintense signal, variable vascular flow voids, and possibly phleboliths, depending upon the type of lesion. The lack of contrast will limit the ability to characterize the type of vessel and characterization of flow through the lesion (high- versus low-flow) and, therefore, the type of VM being evaluated. The addition of IV contrast and possibly MRA may be beneficial to making a more definitive, accurate characterization of the lesion and eventually the diagnosis [31]. Radiography Area of Interest There is no relevant literature to support the use of radiography area of interest as the initial imaging modality for vascular lesions such as tumor or malformation [35]. Radiographs may reveal calcifications within a soft tissue mass, indicating the diagnosis of VM, but is not typically the initial imaging study when a VA is suspected. Phleboliths occur at the site of microshunts in VMs. US Area of Interest US may be used to distinguish characteristic features of VTs and to differentiate between low-flow and fast-flow VMs. Aside from infantile hemangioma, VTs reveal well-defined solid tissue components with variable echotexture [21]. Venous VMs can be partially characterized with grayscale US, and certain features such as multiple anechoic spaces, echogenic phleboliths, and expanded soft tissue spaces that are compressible (muscle, subcutaneous fat, dermis layers) can be diagnostic.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. MRI Area of Interest Without IV Contrast MRI area of interest without IV contrast as the initial imaging modality for vascular lesion such as tumor or malformation may be helpful as the initial imaging examination and may be performed contemporaneously with US to investigate a soft tissue mass or skin discoloration. MRI without IV contrast typically shows a lobulated and often infiltrative soft tissue mass with T1 hypointense and T2 hyperintense signal, variable vascular flow voids, and possibly phleboliths, depending upon the type of lesion. The lack of contrast will limit the ability to characterize the type of vessel and characterization of flow through the lesion (high- versus low-flow) and, therefore, the type of VM being evaluated. The addition of IV contrast and possibly MRA may be beneficial to making a more definitive, accurate characterization of the lesion and eventually the diagnosis [31]. Radiography Area of Interest There is no relevant literature to support the use of radiography area of interest as the initial imaging modality for vascular lesions such as tumor or malformation [35]. Radiographs may reveal calcifications within a soft tissue mass, indicating the diagnosis of VM, but is not typically the initial imaging study when a VA is suspected. Phleboliths occur at the site of microshunts in VMs. US Area of Interest US may be used to distinguish characteristic features of VTs and to differentiate between low-flow and fast-flow VMs. Aside from infantile hemangioma, VTs reveal well-defined solid tissue components with variable echotexture [21]. Venous VMs can be partially characterized with grayscale US, and certain features such as multiple anechoic spaces, echogenic phleboliths, and expanded soft tissue spaces that are compressible (muscle, subcutaneous fat, dermis layers) can be diagnostic.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Lymphatic VMs are also able to be at least partially characterized by grayscale US when multiple anechoic spaces with cysts, which may contain fluid-fluid levels in the event there has been prior infection or hemorrhage into the lesion, that are noncompressible are visualized. Venolymphatic VMs show a combination of the above features. Fast-flow VM-AVMs and AVFs show a cluster of vessels without an associated solid tissue mass [36,37] in contradistinction to hemangiomas. Congenital hepatic hemangiomas are focal lesions of the liver associated with multiple cutaneous infantile hemangiomas. US Area of Interest With IV Contrast US of the abdomen and pelvis with IV contrast, specifically for evaluation of the liver, for the presence of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas may be used to increase sensitivity and diagnostic confidence, particularly for focal lesions, which are seen in congenital hepatic hemangiomas rather than the diffuse and multifocal hepatic hemangiomas seen in infantile hemangiomas [26,27]. The addition of IV contrast for US of the abdomen and pelvis has been shown by El-Ali et al [27] to differentiate infantile hepatic hemangioma in infants from congenital hemangioma of the liver in 5 infants based on the pattern of early and late arterial phase and delayed washout of IV contrast (P = . 0016). The IV contrast enhancement pattern on US was similar to the manner in which the lesions are known to enhance with IV contrast on CT and MRI examinations [28]. US Duplex Doppler Area of Interest US with duplex Doppler may be used to distinguish characteristic features of VTs, verify arterial waveforms in fast- flow VMs (arterialization of draining veins), and differentiate between low-flow and fast-flow VMs. Aside from Soft Tissue Vascular Anomalies-Child infantile hemangioma, VTs typically demonstrate both arterial and venous waveforms.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Lymphatic VMs are also able to be at least partially characterized by grayscale US when multiple anechoic spaces with cysts, which may contain fluid-fluid levels in the event there has been prior infection or hemorrhage into the lesion, that are noncompressible are visualized. Venolymphatic VMs show a combination of the above features. Fast-flow VM-AVMs and AVFs show a cluster of vessels without an associated solid tissue mass [36,37] in contradistinction to hemangiomas. Congenital hepatic hemangiomas are focal lesions of the liver associated with multiple cutaneous infantile hemangiomas. US Area of Interest With IV Contrast US of the abdomen and pelvis with IV contrast, specifically for evaluation of the liver, for the presence of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas may be used to increase sensitivity and diagnostic confidence, particularly for focal lesions, which are seen in congenital hepatic hemangiomas rather than the diffuse and multifocal hepatic hemangiomas seen in infantile hemangiomas [26,27]. The addition of IV contrast for US of the abdomen and pelvis has been shown by El-Ali et al [27] to differentiate infantile hepatic hemangioma in infants from congenital hemangioma of the liver in 5 infants based on the pattern of early and late arterial phase and delayed washout of IV contrast (P = . 0016). The IV contrast enhancement pattern on US was similar to the manner in which the lesions are known to enhance with IV contrast on CT and MRI examinations [28]. US Duplex Doppler Area of Interest US with duplex Doppler may be used to distinguish characteristic features of VTs, verify arterial waveforms in fast- flow VMs (arterialization of draining veins), and differentiate between low-flow and fast-flow VMs. Aside from Soft Tissue Vascular Anomalies-Child infantile hemangioma, VTs typically demonstrate both arterial and venous waveforms.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Venous malformations show multiple anechoic spaces, but the flow in venous VMs may be so slow that it is difficult to perceive on Doppler. Lymphatic VMs are also composed of multiple anechoic spaces with cysts, which may contain fluid-fluid levels in the event there has been prior infection or hemorrhage but will not have Doppler signal. Venolymphatic malformations show a combination of these features. Fast-flow VM-AVMs and AVFs show a cluster of vessels without an associated solid tissue mass [36] with fast-flow on Doppler US. Variant 4: Child. Ultrasound features raise suspicion for vascular malformation. Next imaging study. If initial US imaging raises suspicion for the diagnosis of VM, further imaging is often helpful to visualize the entire extent of the lesion, assess for the presence of multiple lesions, and evaluate possible involvement of adjacent tissues and organs (including sensitive anatomic regions such as deep facial structures, the airway, orbits, and the spine). Arteriography Area of Interest Digital subtraction angiography provides an excellent definition of AVM anatomy, in particular the AVM nidus and the number and definition of feeding arteries and fistulas in fast-flow (arterial) lesions, with greater sensitivity than MRA [38]. Before an invasive procedure such as digital subtraction angiography is performed, it is best to have a narrowed differential diagnosis (usually requires prior MRI/MRA to suggest the diagnosis of a fast-flow VM). Diagnostic angiography may confirm the suspicion of a fast-flow VM if this remains in question following MRI/MRA but is typically reserved for symptomatic patients when simultaneous treatment is a leading consideration.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Venous malformations show multiple anechoic spaces, but the flow in venous VMs may be so slow that it is difficult to perceive on Doppler. Lymphatic VMs are also composed of multiple anechoic spaces with cysts, which may contain fluid-fluid levels in the event there has been prior infection or hemorrhage but will not have Doppler signal. Venolymphatic malformations show a combination of these features. Fast-flow VM-AVMs and AVFs show a cluster of vessels without an associated solid tissue mass [36] with fast-flow on Doppler US. Variant 4: Child. Ultrasound features raise suspicion for vascular malformation. Next imaging study. If initial US imaging raises suspicion for the diagnosis of VM, further imaging is often helpful to visualize the entire extent of the lesion, assess for the presence of multiple lesions, and evaluate possible involvement of adjacent tissues and organs (including sensitive anatomic regions such as deep facial structures, the airway, orbits, and the spine). Arteriography Area of Interest Digital subtraction angiography provides an excellent definition of AVM anatomy, in particular the AVM nidus and the number and definition of feeding arteries and fistulas in fast-flow (arterial) lesions, with greater sensitivity than MRA [38]. Before an invasive procedure such as digital subtraction angiography is performed, it is best to have a narrowed differential diagnosis (usually requires prior MRI/MRA to suggest the diagnosis of a fast-flow VM). Diagnostic angiography may confirm the suspicion of a fast-flow VM if this remains in question following MRI/MRA but is typically reserved for symptomatic patients when simultaneous treatment is a leading consideration.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

CT Area of Interest With IV Contrast Contrast-enhanced CT may provide further anatomic definition of a VM after US in other anatomies, aiding in visualizing phleboliths, thrombus, osseous changes such as erosion or findings related to overgrowth syndromes, and soft tissue involvement, especially in defining the deep or infiltrative extent of a VA [39-41]. CT Area of Interest Without and With IV Contrast There is insufficient literature reviewing the efficacy of CT area of interest without and with IV contrast in this clinical scenario. CT of the chest without and with IV contrast has been used for diagnosis in patients with pulmonary arteriovenous malformations (PAVMs), which are seen in children with hereditary hemorrhagic telangiectasia (HHT), as a follow- up examination for the depiction of precise anatomy of simple and some complex lesions, after initial screening, which may be performed using transthoracic contrast echocardiography, which confirms the presence of a suspected shunt [42]. Both phases of the CT examination may provide important information in the diagnosis of PAVM [42]. Contrast-enhanced CT may provide further anatomic definition of a VM after US in other anatomies, aiding in visualizing phleboliths, thrombus, osseous changes such as erosion or findings related to overgrowth syndromes, and soft tissue involvement, especially in defining the deep or infiltrative extent of a VA [39-41]. CT Area of Interest Without IV Contrast There is no relevant literature reviewing the efficacy of noncontrast enhanced CT evaluation of VM. CT without IV contrast is limited in diagnosis of soft tissue and solid organ VMs and VTs because all structures and tissues show homogenous and similar attenuation, which obscures findings or does not allow characterization of the extent of abnormalities.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. CT Area of Interest With IV Contrast Contrast-enhanced CT may provide further anatomic definition of a VM after US in other anatomies, aiding in visualizing phleboliths, thrombus, osseous changes such as erosion or findings related to overgrowth syndromes, and soft tissue involvement, especially in defining the deep or infiltrative extent of a VA [39-41]. CT Area of Interest Without and With IV Contrast There is insufficient literature reviewing the efficacy of CT area of interest without and with IV contrast in this clinical scenario. CT of the chest without and with IV contrast has been used for diagnosis in patients with pulmonary arteriovenous malformations (PAVMs), which are seen in children with hereditary hemorrhagic telangiectasia (HHT), as a follow- up examination for the depiction of precise anatomy of simple and some complex lesions, after initial screening, which may be performed using transthoracic contrast echocardiography, which confirms the presence of a suspected shunt [42]. Both phases of the CT examination may provide important information in the diagnosis of PAVM [42]. Contrast-enhanced CT may provide further anatomic definition of a VM after US in other anatomies, aiding in visualizing phleboliths, thrombus, osseous changes such as erosion or findings related to overgrowth syndromes, and soft tissue involvement, especially in defining the deep or infiltrative extent of a VA [39-41]. CT Area of Interest Without IV Contrast There is no relevant literature reviewing the efficacy of noncontrast enhanced CT evaluation of VM. CT without IV contrast is limited in diagnosis of soft tissue and solid organ VMs and VTs because all structures and tissues show homogenous and similar attenuation, which obscures findings or does not allow characterization of the extent of abnormalities.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

CTA and CTV Area of Interest With IV Contrast CTA and CTV of the upper extremity was shown by Henzler et al [44] to be the superior imaging modality compared with MRI and US because it provides images with high spatial resolution for excellent delineation of the anatomy and extent of VTs and VMs, providing a vascular map of the lesion for use in treatment planning. Soft Tissue Vascular Anomalies-Child CTA of the chest, using a modified pulmonary CTA and CTV protocol, is used to optimally show the feeding artery, nidus, and draining vein components of the PAVM [42]. CTA and CTV may provide further anatomic definition of a VM after US in other anatomies, aiding in visualizing phleboliths, thrombus, osseous changes such as erosion or findings related to overgrowth syndromes, and soft tissue involvement, especially in defining the deep or infiltrative extent of a VA [39-41,45]. MRA and MRV Area of Interest Without and With IV Contrast MRA of the area of interest without and with IV contrast may be used to define venous and arterial anatomy, as well as better differentiate the tissue types involved in the VM. MRA and MRV of the area of interest without IV contrast, using flow-dependent or flow-independent techniques, can be used as well. For example, Relaxation- Enhanced Angiography without Contrast and Triggering, a flow-independent T2-weighted noncontrast-enhanced MRA sequence, has been shown to be effective for defining the anatomy of major feeding arteries and draining veins and correlation with contrast-enhanced MRA and MRV [32,46]. Contrast-enhanced 3-D and 4-D dynamic MRA acquisitions are helpful in distinguishing whether flow through the lesion is slow or fast, arterial and venous anatomy, the location of a nidus in an AVM, and the site of vascular fistula in an AVF.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. CTA and CTV Area of Interest With IV Contrast CTA and CTV of the upper extremity was shown by Henzler et al [44] to be the superior imaging modality compared with MRI and US because it provides images with high spatial resolution for excellent delineation of the anatomy and extent of VTs and VMs, providing a vascular map of the lesion for use in treatment planning. Soft Tissue Vascular Anomalies-Child CTA of the chest, using a modified pulmonary CTA and CTV protocol, is used to optimally show the feeding artery, nidus, and draining vein components of the PAVM [42]. CTA and CTV may provide further anatomic definition of a VM after US in other anatomies, aiding in visualizing phleboliths, thrombus, osseous changes such as erosion or findings related to overgrowth syndromes, and soft tissue involvement, especially in defining the deep or infiltrative extent of a VA [39-41,45]. MRA and MRV Area of Interest Without and With IV Contrast MRA of the area of interest without and with IV contrast may be used to define venous and arterial anatomy, as well as better differentiate the tissue types involved in the VM. MRA and MRV of the area of interest without IV contrast, using flow-dependent or flow-independent techniques, can be used as well. For example, Relaxation- Enhanced Angiography without Contrast and Triggering, a flow-independent T2-weighted noncontrast-enhanced MRA sequence, has been shown to be effective for defining the anatomy of major feeding arteries and draining veins and correlation with contrast-enhanced MRA and MRV [32,46]. Contrast-enhanced 3-D and 4-D dynamic MRA acquisitions are helpful in distinguishing whether flow through the lesion is slow or fast, arterial and venous anatomy, the location of a nidus in an AVM, and the site of vascular fistula in an AVF.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Dynamic MRA combined with contrast-enhanced MRI has been shown to have excellent sensitivity (83%) and specificity (95%) in differentiating low-flow from fast-flow VMs [29,47]. Dynamic 4-D MRA with IV contrast may be used to detect presence of arteriovenous microshunts in VMs, which have been found to be associated with presence of phleboliths [30]. MRI Area of Interest Without and With IV Contrast MRI of the area of interest without and with IV contrast may be used to define the deep and superficial extent of VM using T1-weighted sequences, and T2-weighted images reveal vascular flow voids as well as fluid filled spaces. Areas of signal loss or flow voids are important to document and can help drive the diagnosis (phleboliths versus fast-flow vessels). A well-defined soft tissue mass is not typically identified in AVM. IV contrast shows intense enhancement of involved soft tissues, cyst walls, and/or vascular structures [31]. MRI Area of Interest Without IV Contrast There is no relevant literature to support the use of MRI area of interest without IV contrast as the next imaging modality for vascular lesion such as tumor or malformation. Radiography Area of Interest There is no relevant literature to support the use of radiography area of interest as the next imaging modality for VMs [35]. US Area of Interest With IV Contrast There is no relevant literature to support the use of US area of interest with IV contrast as the initial imaging modality for patients with vascular lesions such as tumor or malformation [48]. Variant 5: Child. Established diagnosis of vascular malformation presenting with new or persistent signs or symptoms. Initial imaging. VMs are a diverse group of lesions, which are difficult to treat, requiring multiple episodes of interventional embolization/sclerotherapy and or surgical intervention over years of treatment.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Dynamic MRA combined with contrast-enhanced MRI has been shown to have excellent sensitivity (83%) and specificity (95%) in differentiating low-flow from fast-flow VMs [29,47]. Dynamic 4-D MRA with IV contrast may be used to detect presence of arteriovenous microshunts in VMs, which have been found to be associated with presence of phleboliths [30]. MRI Area of Interest Without and With IV Contrast MRI of the area of interest without and with IV contrast may be used to define the deep and superficial extent of VM using T1-weighted sequences, and T2-weighted images reveal vascular flow voids as well as fluid filled spaces. Areas of signal loss or flow voids are important to document and can help drive the diagnosis (phleboliths versus fast-flow vessels). A well-defined soft tissue mass is not typically identified in AVM. IV contrast shows intense enhancement of involved soft tissues, cyst walls, and/or vascular structures [31]. MRI Area of Interest Without IV Contrast There is no relevant literature to support the use of MRI area of interest without IV contrast as the next imaging modality for vascular lesion such as tumor or malformation. Radiography Area of Interest There is no relevant literature to support the use of radiography area of interest as the next imaging modality for VMs [35]. US Area of Interest With IV Contrast There is no relevant literature to support the use of US area of interest with IV contrast as the initial imaging modality for patients with vascular lesions such as tumor or malformation [48]. Variant 5: Child. Established diagnosis of vascular malformation presenting with new or persistent signs or symptoms. Initial imaging. VMs are a diverse group of lesions, which are difficult to treat, requiring multiple episodes of interventional embolization/sclerotherapy and or surgical intervention over years of treatment.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Before and throughout the treatment course, interval imaging may help for monitoring regression of the lesion and planning approach to the next treatment session. Arteriography Area of Interest There is no relevant literature to support the use of arteriography as the initial diagnostic imaging modality for patients with an established diagnosis of a low-flow VM. In patients with a fast-flow VM, angiography is useful to characterize new or persistent signs or symptoms (recurrent bleeding events, ischemic changes to normal tissues, etc) when simultaneous treatment is planned [49]. CT Area of Interest With IV Contrast Although contrast-enhanced CT may provide anatomic definition of a VM if there are persistent anatomical questions after MRI/MRA, there is no relevant literature to support the use of CT area of interest with IV contrast Soft Tissue Vascular Anomalies-Child as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms [39]. CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT area of interest without and with IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT area of interest without IV contrast a as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. CTA and CTV Area of Interest With IV Contrast There is no relevant literature to support the use of CTA and CTV area of interest with IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Before and throughout the treatment course, interval imaging may help for monitoring regression of the lesion and planning approach to the next treatment session. Arteriography Area of Interest There is no relevant literature to support the use of arteriography as the initial diagnostic imaging modality for patients with an established diagnosis of a low-flow VM. In patients with a fast-flow VM, angiography is useful to characterize new or persistent signs or symptoms (recurrent bleeding events, ischemic changes to normal tissues, etc) when simultaneous treatment is planned [49]. CT Area of Interest With IV Contrast Although contrast-enhanced CT may provide anatomic definition of a VM if there are persistent anatomical questions after MRI/MRA, there is no relevant literature to support the use of CT area of interest with IV contrast Soft Tissue Vascular Anomalies-Child as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms [39]. CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT area of interest without and with IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT area of interest without IV contrast a as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. CTA and CTV Area of Interest With IV Contrast There is no relevant literature to support the use of CTA and CTV area of interest with IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms.

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

MRA and MRV Area of Interest Without and With IV Contrast MRA and MRV of the area of interest without and with IV contrast may be used to update venous and arterial anatomy as well as better differentiate the tissue types involved in the VM. As embolization and sclerotherapy treatments change the vascular channels, MRA can provide updated information. Contrast-enhanced 3-D and 4-D dynamic MRA acquisitions are helpful in assessing flow through the lesion before and after treatment, the location of a new nidus in an AVM, and a new vascular fistula in an AVF. Dynamic MRA and MRV combined with contrast-enhanced MRI has been shown to have excellent sensitivity (83%) and specificity (95%) in differentiating low-flow from fast-flow VMs [29,47]. Embolization and sclerotherapy are expected to change the shunting within these low-flow VMs. MRI Area of Interest Without and With IV Contrast MRI of the area of interest without and with IV contrast may be used to define the deep and superficial extent of VM with expected treatment changes. IV contrast shows intense enhancement of involved soft tissues, cyst walls, and/or vascular structures [31]. Particular attention may need to be paid to imaging findings that may suggest treatment complications (abscess, tissue necrosis, cellulitis, deep vein thrombosis, etc). MRI Area of Interest Without IV Contrast There is no relevant literature to support the use of MRI area of interest without IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. Radiography Area of Interest Radiographs of the area of interest may reveal calcified phleboliths and embolization material within a previously treated VM; these findings may be helpful in choosing a follow-up imaging study (ie, US for suspected occluded deep vein after sclerotherapy).

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. MRA and MRV Area of Interest Without and With IV Contrast MRA and MRV of the area of interest without and with IV contrast may be used to update venous and arterial anatomy as well as better differentiate the tissue types involved in the VM. As embolization and sclerotherapy treatments change the vascular channels, MRA can provide updated information. Contrast-enhanced 3-D and 4-D dynamic MRA acquisitions are helpful in assessing flow through the lesion before and after treatment, the location of a new nidus in an AVM, and a new vascular fistula in an AVF. Dynamic MRA and MRV combined with contrast-enhanced MRI has been shown to have excellent sensitivity (83%) and specificity (95%) in differentiating low-flow from fast-flow VMs [29,47]. Embolization and sclerotherapy are expected to change the shunting within these low-flow VMs. MRI Area of Interest Without and With IV Contrast MRI of the area of interest without and with IV contrast may be used to define the deep and superficial extent of VM with expected treatment changes. IV contrast shows intense enhancement of involved soft tissues, cyst walls, and/or vascular structures [31]. Particular attention may need to be paid to imaging findings that may suggest treatment complications (abscess, tissue necrosis, cellulitis, deep vein thrombosis, etc). MRI Area of Interest Without IV Contrast There is no relevant literature to support the use of MRI area of interest without IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. Radiography Area of Interest Radiographs of the area of interest may reveal calcified phleboliths and embolization material within a previously treated VM; these findings may be helpful in choosing a follow-up imaging study (ie, US for suspected occluded deep vein after sclerotherapy).

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Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child

Radiographs may also better characterize imaging artifacts (embolization coils), which may limit the evaluation of residual VM on MRI/US [35]. US Area of Interest US area of interest may be useful as an initial imaging modality in patients with an established diagnosis of VM when presenting with new or persistent signs or symptoms. However, US may be limited if there is extensive embolization material present. VM occlusions directly due to embolization versus associated soft tissue swelling from treatment changes can be visualized on grayscale US. US Area of Interest With IV Contrast There is no relevant literature to support the use of US area of interest with IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. It has been shown that the dynamics of blood flow through VM can be determined using contrast-enhanced US, and that differences in blood flow dynamics as measured using time intensity curve analysis can be shown by comparing pretreatment and post-treatment examinations [50]. US Duplex Doppler Area of Interest US with duplex Doppler may be helpful as an initial imaging modality in patients with an established diagnosis of VM when presenting with new or persistent signs or symptoms. Doppler US can help distinguish changes following Soft Tissue Vascular Anomalies-Child enhanced US and that differences in blood flow dynamics as measured using time intensity curve analysis can be shown by comparing pretreatment and post-treatment examinations. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www. acr.org/ac.

Soft Tissue Vascular Anomalies Vascular Malformations and Infantile Vascular Tumors Non CNS Child. Radiographs may also better characterize imaging artifacts (embolization coils), which may limit the evaluation of residual VM on MRI/US [35]. US Area of Interest US area of interest may be useful as an initial imaging modality in patients with an established diagnosis of VM when presenting with new or persistent signs or symptoms. However, US may be limited if there is extensive embolization material present. VM occlusions directly due to embolization versus associated soft tissue swelling from treatment changes can be visualized on grayscale US. US Area of Interest With IV Contrast There is no relevant literature to support the use of US area of interest with IV contrast as the initial imaging modality for patients with an established diagnosis of VM presenting with new or persistent signs and symptoms. It has been shown that the dynamics of blood flow through VM can be determined using contrast-enhanced US, and that differences in blood flow dynamics as measured using time intensity curve analysis can be shown by comparing pretreatment and post-treatment examinations [50]. US Duplex Doppler Area of Interest US with duplex Doppler may be helpful as an initial imaging modality in patients with an established diagnosis of VM when presenting with new or persistent signs or symptoms. Doppler US can help distinguish changes following Soft Tissue Vascular Anomalies-Child enhanced US and that differences in blood flow dynamics as measured using time intensity curve analysis can be shown by comparing pretreatment and post-treatment examinations. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www. acr.org/ac.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Introduction/Background Neoadjuvant chemotherapy (NAC) is often given before definitive surgical intervention for locally advanced breast cancer, which is defined as a tumor >5 cm with regional and/or metastatic lymph nodes, skin, or chest wall involvement. NAC is also indicated in T2 tumors (2-5 cm) in which lumpectomy might result in substantial cosmetic defect, triple-negative tumors 2 to 5 cm in size even if node-negative, and human epidermal growth factor receptor 2 (HER2)/neu-positive tumors 2 to 5 cm in size even if node-negative. The primary aims of this approach are to 1) reduce tumor burden, thereby permitting breast conservation rather than mastectomy; 2) promptly treat possible metastatic disease, whether or not it is detectable on preoperative staging; and 3) potentially tailor future chemotherapeutic decisions by monitoring in vivo tumor response [1,2]. Although the overall and disease-free survival for women receiving neoadjuvant versus adjuvant chemotherapy are not substantially different, women who do receive neoadjuvant therapy are less likely to undergo mastectomy and are more likely to be treated with breast conservation [1]. Imaging plays a vital role in managing patients undergoing NAC as treatment decisions rely heavily on accurate assessment of response to therapy. Beyond assessing the primary lesion, imaging is used to stage and monitor patients before, during, and after completion of initial therapy, including the axilla and potential distant metastatic sites. Accurate assessment of tumor burden is critical in determining the best management. Imaging plays an important role as clinical breast examination is challenging for primary tumors that are <2 cm in size, have an irregular shape or ill-defined margins, and show necrosis, fibrosis, or fragmentation with treatment [3]. Axillary imaging is increasingly used before, during, and after therapy to monitor response to treatment and help guide surgical management [4].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Introduction/Background Neoadjuvant chemotherapy (NAC) is often given before definitive surgical intervention for locally advanced breast cancer, which is defined as a tumor >5 cm with regional and/or metastatic lymph nodes, skin, or chest wall involvement. NAC is also indicated in T2 tumors (2-5 cm) in which lumpectomy might result in substantial cosmetic defect, triple-negative tumors 2 to 5 cm in size even if node-negative, and human epidermal growth factor receptor 2 (HER2)/neu-positive tumors 2 to 5 cm in size even if node-negative. The primary aims of this approach are to 1) reduce tumor burden, thereby permitting breast conservation rather than mastectomy; 2) promptly treat possible metastatic disease, whether or not it is detectable on preoperative staging; and 3) potentially tailor future chemotherapeutic decisions by monitoring in vivo tumor response [1,2]. Although the overall and disease-free survival for women receiving neoadjuvant versus adjuvant chemotherapy are not substantially different, women who do receive neoadjuvant therapy are less likely to undergo mastectomy and are more likely to be treated with breast conservation [1]. Imaging plays a vital role in managing patients undergoing NAC as treatment decisions rely heavily on accurate assessment of response to therapy. Beyond assessing the primary lesion, imaging is used to stage and monitor patients before, during, and after completion of initial therapy, including the axilla and potential distant metastatic sites. Accurate assessment of tumor burden is critical in determining the best management. Imaging plays an important role as clinical breast examination is challenging for primary tumors that are <2 cm in size, have an irregular shape or ill-defined margins, and show necrosis, fibrosis, or fragmentation with treatment [3]. Axillary imaging is increasingly used before, during, and after therapy to monitor response to treatment and help guide surgical management [4].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Most practices define response per Response Evaluation Criteria in Solid Tumors (RECIST) or RECIST 1, which defines complete response (CR) as disappearance of the tumor in its entirety, partial response (PR) as at least 30% decrease in the longest diameter of the tumor compared with pretreatment baseline, progression of disease as at least 20% increase in longest diameter, and stable disease as no change in the tumor size that would qualify as PR or progression of disease on the basis of longest diameter [5]. Pathologic complete response (pCR) is defined as a surgical specimen free of carcinoma following therapy and represents a surrogate endpoint for treatment with pCR predicting improved disease-free survival [1,6]. Although there is a paucity of published data in men and transgender patients diagnosed with breast cancer, in practice, these patients are managed similarly to women. Special Imaging Considerations There are several single-institution studies that demonstrate contrast-enhanced mammography has comparable sensitivity and specificity to contrast-enhanced MRI in evaluating for residual disease after NAC [7-10]. Therefore, although not widely used in clinical practice, this may be an option for patients who are unable to undergo MRI [7- 10]. aUniversity of California San Francisco, San Francisco, California. bResearch Author, University of California San Francisco, San Francisco, California. cPanel Chair, New York University Grossman School of Medicine, New York, New York. dPanel Vice-Chair, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania. eBoston Medical Center, Boston, Massachusetts, Primary care physician. fHackensack University Medical Center, Hackensack, New Jersey; American College of Surgeons. gUniversity of North Carolina Hospital, Chapel Hill, North Carolina. hElizabeth Wende Breast Care, Rochester, New York.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Most practices define response per Response Evaluation Criteria in Solid Tumors (RECIST) or RECIST 1, which defines complete response (CR) as disappearance of the tumor in its entirety, partial response (PR) as at least 30% decrease in the longest diameter of the tumor compared with pretreatment baseline, progression of disease as at least 20% increase in longest diameter, and stable disease as no change in the tumor size that would qualify as PR or progression of disease on the basis of longest diameter [5]. Pathologic complete response (pCR) is defined as a surgical specimen free of carcinoma following therapy and represents a surrogate endpoint for treatment with pCR predicting improved disease-free survival [1,6]. Although there is a paucity of published data in men and transgender patients diagnosed with breast cancer, in practice, these patients are managed similarly to women. Special Imaging Considerations There are several single-institution studies that demonstrate contrast-enhanced mammography has comparable sensitivity and specificity to contrast-enhanced MRI in evaluating for residual disease after NAC [7-10]. Therefore, although not widely used in clinical practice, this may be an option for patients who are unable to undergo MRI [7- 10]. aUniversity of California San Francisco, San Francisco, California. bResearch Author, University of California San Francisco, San Francisco, California. cPanel Chair, New York University Grossman School of Medicine, New York, New York. dPanel Vice-Chair, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania. eBoston Medical Center, Boston, Massachusetts, Primary care physician. fHackensack University Medical Center, Hackensack, New Jersey; American College of Surgeons. gUniversity of North Carolina Hospital, Chapel Hill, North Carolina. hElizabeth Wende Breast Care, Rochester, New York.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

iUniversity of Wisconsin School of Medicine & Public Health, Madison, Wisconsin. jSanford Health of Northern Minnesota, Bemidji, Minnesota. kUniversity of Washington, Seattle, Washington. lMayo Clinic, Phoenix, Arizona. mLoyola University Chicago, Stritch School of Medicine, Department of Radiation Oncology, Cardinal Bernardin Cancer Center, Maywood, Illinois. nHoag Family Cancer Institute, Newport Beach, California and University of Southern California, Los Angeles, California; Commission on Nuclear Medicine and Molecular Imaging. oSpecialty Chair, Boston University School of Medicine, Boston, Massachusetts. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] OR Discussion of Procedures by Variant Variant 1: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer. Initial determination of tumor size and extent within the breast prior to neoadjuvant chemotherapy. Initial imaging. Digital Breast Tomosynthesis Diagnostic Mammography, ultrasound (US), and MRI are complementary modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [1,11-15]. Mammography and US are the two main modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [11-15]. Mammography is most accurate for ductal and low-grade malignancies and less accurate for invasive lobular cancers and higher-grade lesions [11-16].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. iUniversity of Wisconsin School of Medicine & Public Health, Madison, Wisconsin. jSanford Health of Northern Minnesota, Bemidji, Minnesota. kUniversity of Washington, Seattle, Washington. lMayo Clinic, Phoenix, Arizona. mLoyola University Chicago, Stritch School of Medicine, Department of Radiation Oncology, Cardinal Bernardin Cancer Center, Maywood, Illinois. nHoag Family Cancer Institute, Newport Beach, California and University of Southern California, Los Angeles, California; Commission on Nuclear Medicine and Molecular Imaging. oSpecialty Chair, Boston University School of Medicine, Boston, Massachusetts. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] OR Discussion of Procedures by Variant Variant 1: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer. Initial determination of tumor size and extent within the breast prior to neoadjuvant chemotherapy. Initial imaging. Digital Breast Tomosynthesis Diagnostic Mammography, ultrasound (US), and MRI are complementary modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [1,11-15]. Mammography and US are the two main modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [11-15]. Mammography is most accurate for ductal and low-grade malignancies and less accurate for invasive lobular cancers and higher-grade lesions [11-16].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Digital breast tomosynthesis (DBT) addresses some of the limitations encountered with standard mammographic views. In addition to planar images, DBT creates thin-section reconstructed images, which decreases the lesion- masking effect of overlapping normal tissue. In the screening setting, some authors found the advantages of DBT to be especially pronounced in patients <50 years of age [17,18], in patients with dense breasts [17,19], and with lesion types including spiculated masses, [20] asymmetries [21], and architectural distortion [22]. DBT is also useful in the diagnostic setting, improving lesion characterization [22-25] in noncalcified lesions compared with conventional mammography. A prospective study of 166 patients with breast cancer compared digital mammography (DM) to combined DM plus DBT for accuracy of local tumor staging. They demonstrated better accuracy of DM plus DBT for detecting additional ipsilateral and contralateral disease in patients with nondense breasts [26]. A retrospective study of 222 cancers demonstrated that pathologic response to NAC was less likely with the baseline mammographic finding of spiculation [27]. Because of the presence of dense tissue in up to 50% of patients, obscured margins may limit evaluation of the extent of disease [28]. Therefore, mammography or DBT is most often combined with other modalities, such as US or MRI, to guide clinical management. FDG-PET/CT Skull Base to Mid-Thigh Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT has a low sensitivity for detection of primary breast cancer because of the low spatial resolution of the scanners and the relatively low FDG uptake of both invasive lobular cancers and low-grade malignancies [29,30]. As a result, this modality is not routinely used for pretreatment imaging of the primary breast tumor.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Digital breast tomosynthesis (DBT) addresses some of the limitations encountered with standard mammographic views. In addition to planar images, DBT creates thin-section reconstructed images, which decreases the lesion- masking effect of overlapping normal tissue. In the screening setting, some authors found the advantages of DBT to be especially pronounced in patients <50 years of age [17,18], in patients with dense breasts [17,19], and with lesion types including spiculated masses, [20] asymmetries [21], and architectural distortion [22]. DBT is also useful in the diagnostic setting, improving lesion characterization [22-25] in noncalcified lesions compared with conventional mammography. A prospective study of 166 patients with breast cancer compared digital mammography (DM) to combined DM plus DBT for accuracy of local tumor staging. They demonstrated better accuracy of DM plus DBT for detecting additional ipsilateral and contralateral disease in patients with nondense breasts [26]. A retrospective study of 222 cancers demonstrated that pathologic response to NAC was less likely with the baseline mammographic finding of spiculation [27]. Because of the presence of dense tissue in up to 50% of patients, obscured margins may limit evaluation of the extent of disease [28]. Therefore, mammography or DBT is most often combined with other modalities, such as US or MRI, to guide clinical management. FDG-PET/CT Skull Base to Mid-Thigh Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT has a low sensitivity for detection of primary breast cancer because of the low spatial resolution of the scanners and the relatively low FDG uptake of both invasive lobular cancers and low-grade malignancies [29,30]. As a result, this modality is not routinely used for pretreatment imaging of the primary breast tumor.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Mammography Diagnostic Mammography, US, and MRI are complementary modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [1,11-15]. Mammography is most accurate for ductal and low-grade malignancies and less accurate for invasive lobular cancers and higher-grade lesions [11-16]. DBT addresses some of the limitations encountered with standard mammographic views. In addition to planar images, DBT creates thin-section reconstructed images, which decreases the lesion-masking effect of overlapping normal tissue. In the screening setting, some authors found the advantages of DBT to be especially pronounced in patients <50 years of age [17,18], in patients with dense breasts [17,19], and with lesion types including spiculated masses [20] and asymmetries [21]. DBT can also be useful in the diagnostic setting, improving lesion characterization [22-25] in noncalcified lesions compared with conventional mammography. Monitoring Response to Neoadjuvant Chemotherapy A prospective study of 166 patients with breast cancer compared DM to combined DM plus DBT for accuracy of local tumor staging. They demonstrated better accuracy of DM plus DBT for detecting additional ipsilateral and contralateral disease in patients with nondense breasts [26]. A retrospective study of 222 cancers demonstrated that pathologic response to NAC was less likely with the baseline mammographic finding of spiculation [27]. Because of the presence of dense tissue in up to 50% of patients, obscured margins may limit evaluation of the extent of disease [28]. Therefore, mammography or DBT is most often combined with other modalities, such as US or MRI, to guide clinical management. MRI Breast Without and With IV Contrast MRI is complementary to mammography and US for assessing tumor size before treatment. MRI permits evaluation of a viable tumor before and after NAC by detecting changes in tumor vascularity [31].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Mammography Diagnostic Mammography, US, and MRI are complementary modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [1,11-15]. Mammography is most accurate for ductal and low-grade malignancies and less accurate for invasive lobular cancers and higher-grade lesions [11-16]. DBT addresses some of the limitations encountered with standard mammographic views. In addition to planar images, DBT creates thin-section reconstructed images, which decreases the lesion-masking effect of overlapping normal tissue. In the screening setting, some authors found the advantages of DBT to be especially pronounced in patients <50 years of age [17,18], in patients with dense breasts [17,19], and with lesion types including spiculated masses [20] and asymmetries [21]. DBT can also be useful in the diagnostic setting, improving lesion characterization [22-25] in noncalcified lesions compared with conventional mammography. Monitoring Response to Neoadjuvant Chemotherapy A prospective study of 166 patients with breast cancer compared DM to combined DM plus DBT for accuracy of local tumor staging. They demonstrated better accuracy of DM plus DBT for detecting additional ipsilateral and contralateral disease in patients with nondense breasts [26]. A retrospective study of 222 cancers demonstrated that pathologic response to NAC was less likely with the baseline mammographic finding of spiculation [27]. Because of the presence of dense tissue in up to 50% of patients, obscured margins may limit evaluation of the extent of disease [28]. Therefore, mammography or DBT is most often combined with other modalities, such as US or MRI, to guide clinical management. MRI Breast Without and With IV Contrast MRI is complementary to mammography and US for assessing tumor size before treatment. MRI permits evaluation of a viable tumor before and after NAC by detecting changes in tumor vascularity [31].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

There is substantial evidence to support the routine use of contrast-enhanced MRI to stage, monitor early response, and assess for residual and recurrent disease given the overall high sensitivity and relatively high specificity of this technique [1]. Dynamic contrast-enhanced MRI is a sensitive tool to determine extent of disease in the breast, especially in young patients (<50 years of age), with sensitivity approaching 90% and specificity ranging between 50% and 97% [1,32]. To accurately evaluate for response to NAC, a pretreatment MRI must be obtained to serve as a baseline for comparison. MRI is particularly useful in the assessment of multifocal and multicentric disease, which is often underestimated on both mammography and US [28]. In fact, multifocal and multicentric disease are detected in up to 16% of patients on staging MRI according to a study by Houssami et al [33]. A prospective study of 216 patients demonstrated that size determination on MRI was superior to clinical examination in predicting pathologic response both before, during, and after completion of NAC [31]. The enhancement pattern on the pretreatment MRI also indicates how reliable this technique will be in evaluating response. Nonmass enhancement on the pretreatment MRI has been shown to reveal a scattered cell pattern more commonly on posttreatment imaging, thereby making assessment of residual disease more difficult [34]. However, when a mass with well-defined margins is seen, MRI can more accurately predict the amount of residual disease on posttreatment imaging [34]. In addition, several studies have shown that MRI is more accurate than mammography and US in defining disease extent for invasive lobular cancer [32,35,36]. MRI can reliably assess the chest wall because pectoral or intercostal muscle enhancement correlates well with invasion [37].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. There is substantial evidence to support the routine use of contrast-enhanced MRI to stage, monitor early response, and assess for residual and recurrent disease given the overall high sensitivity and relatively high specificity of this technique [1]. Dynamic contrast-enhanced MRI is a sensitive tool to determine extent of disease in the breast, especially in young patients (<50 years of age), with sensitivity approaching 90% and specificity ranging between 50% and 97% [1,32]. To accurately evaluate for response to NAC, a pretreatment MRI must be obtained to serve as a baseline for comparison. MRI is particularly useful in the assessment of multifocal and multicentric disease, which is often underestimated on both mammography and US [28]. In fact, multifocal and multicentric disease are detected in up to 16% of patients on staging MRI according to a study by Houssami et al [33]. A prospective study of 216 patients demonstrated that size determination on MRI was superior to clinical examination in predicting pathologic response both before, during, and after completion of NAC [31]. The enhancement pattern on the pretreatment MRI also indicates how reliable this technique will be in evaluating response. Nonmass enhancement on the pretreatment MRI has been shown to reveal a scattered cell pattern more commonly on posttreatment imaging, thereby making assessment of residual disease more difficult [34]. However, when a mass with well-defined margins is seen, MRI can more accurately predict the amount of residual disease on posttreatment imaging [34]. In addition, several studies have shown that MRI is more accurate than mammography and US in defining disease extent for invasive lobular cancer [32,35,36]. MRI can reliably assess the chest wall because pectoral or intercostal muscle enhancement correlates well with invasion [37].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Finally, several studies have shown that up to 3% of patients have unsuspected contralateral disease at the time of initial diagnosis and MRI has been proven effective in detecting such contralateral disease [38]. MRI Breast Without IV Contrast A small study of 71 patients with MRI before and after treatment found no significant difference in lesion size interpretation on unenhanced versus enhanced MRI sequences [39]. However, there is insufficient literature to support the use of MRI without intravenous (IV) contrast in initial imaging evaluation of tumor size and extent in the breast before NAC. Sestamibi MBI A few institutions routinely image newly diagnosed breast cancer with molecular breast imaging (MBI) using Tc- 99m sestamibi, which is also sometimes referred to as scintimammography. This functional imaging technique reflects cell metabolism by accumulating in active mitochondrial cells. A prospective study of 90 patients found the longest dimension of the cancer measured on MRI was within 1 cm of that on MBI in 72% of cases and concluded that MBI may be an option for patients with contraindication to MRI [40,41]. However, there is insufficient literature to support the routine use of sestamibi MBI in initial imaging evaluation of tumor size and extent in the breast before NAC. US Breast Mammography, US, and MRI are complementary modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [1,11-15]. US is more accurate in measuring tumor size than clinical breast examination or mammography. It is most often performed in conjunction with mammography and is more accurate in assessing tumor size [16,42]. Monitoring Response to Neoadjuvant Chemotherapy Variant 2: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer. Imaging of the breast after initiation or completion of neoadjuvant chemotherapy. Initial imaging.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Finally, several studies have shown that up to 3% of patients have unsuspected contralateral disease at the time of initial diagnosis and MRI has been proven effective in detecting such contralateral disease [38]. MRI Breast Without IV Contrast A small study of 71 patients with MRI before and after treatment found no significant difference in lesion size interpretation on unenhanced versus enhanced MRI sequences [39]. However, there is insufficient literature to support the use of MRI without intravenous (IV) contrast in initial imaging evaluation of tumor size and extent in the breast before NAC. Sestamibi MBI A few institutions routinely image newly diagnosed breast cancer with molecular breast imaging (MBI) using Tc- 99m sestamibi, which is also sometimes referred to as scintimammography. This functional imaging technique reflects cell metabolism by accumulating in active mitochondrial cells. A prospective study of 90 patients found the longest dimension of the cancer measured on MRI was within 1 cm of that on MBI in 72% of cases and concluded that MBI may be an option for patients with contraindication to MRI [40,41]. However, there is insufficient literature to support the routine use of sestamibi MBI in initial imaging evaluation of tumor size and extent in the breast before NAC. US Breast Mammography, US, and MRI are complementary modalities for assessing primary tumor size before treatment because they are reliable tools to determine tumor size at diagnosis [1,11-15]. US is more accurate in measuring tumor size than clinical breast examination or mammography. It is most often performed in conjunction with mammography and is more accurate in assessing tumor size [16,42]. Monitoring Response to Neoadjuvant Chemotherapy Variant 2: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer. Imaging of the breast after initiation or completion of neoadjuvant chemotherapy. Initial imaging.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Digital Breast Tomosynthesis Diagnostic Although mammography, DBT, and US are reliable for determining tumor size at diagnosis [11-15], changes within the tumor secondary to NAC may be difficult to evaluate after treatment is initiated. It is well known that tumoral changes related to necrosis, fragmentation, and fibrosis make it difficult for mammography, DBT, and US to accurately determine residual tumor burden [43,44]. In a retrospective study of 445 patients who underwent NAC, mammography was 94% sensitive and 50% specific for predicting residual disease in the breast. In cases presenting as mass lesions, 95% of masses decreased in mammographic size with treatment. However, there was correlation between mammographic size and surgical pathology in only 60% of cases [45]. One study found that if >50% of the margin of the primary lesion was mammographically visible at baseline, posttreatment mammographic imaging was a reliable tool for determining lesion size [28,46]. In a study of 56 patients, mammography was 79% sensitive and 77% specific in predicting residual disease after therapy, performing better than clinical breast examination [47]. The extent of calcifications on mammography after therapy does not correlate well with residual tumor burden and is overestimated in up to 45% of patients [48-50]. Therefore, it is not a reliable marker of remaining viable tumor. In a study including 139 patients with baseline mammographic calcifications, residual calcifications were present on all posttreatment mammograms [45]. Estrogen receptor (ER)-positive tumors are more likely than ER-negative tumors to have residual malignant calcifications on mammography after treatment, whereas triple-negative tumors are the least likely to have residual malignant calcifications after therapy, suggesting that different tumor subtypes may warrant different approaches [48,51].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Digital Breast Tomosynthesis Diagnostic Although mammography, DBT, and US are reliable for determining tumor size at diagnosis [11-15], changes within the tumor secondary to NAC may be difficult to evaluate after treatment is initiated. It is well known that tumoral changes related to necrosis, fragmentation, and fibrosis make it difficult for mammography, DBT, and US to accurately determine residual tumor burden [43,44]. In a retrospective study of 445 patients who underwent NAC, mammography was 94% sensitive and 50% specific for predicting residual disease in the breast. In cases presenting as mass lesions, 95% of masses decreased in mammographic size with treatment. However, there was correlation between mammographic size and surgical pathology in only 60% of cases [45]. One study found that if >50% of the margin of the primary lesion was mammographically visible at baseline, posttreatment mammographic imaging was a reliable tool for determining lesion size [28,46]. In a study of 56 patients, mammography was 79% sensitive and 77% specific in predicting residual disease after therapy, performing better than clinical breast examination [47]. The extent of calcifications on mammography after therapy does not correlate well with residual tumor burden and is overestimated in up to 45% of patients [48-50]. Therefore, it is not a reliable marker of remaining viable tumor. In a study including 139 patients with baseline mammographic calcifications, residual calcifications were present on all posttreatment mammograms [45]. Estrogen receptor (ER)-positive tumors are more likely than ER-negative tumors to have residual malignant calcifications on mammography after treatment, whereas triple-negative tumors are the least likely to have residual malignant calcifications after therapy, suggesting that different tumor subtypes may warrant different approaches [48,51].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

There is no relevant literature specifically comparing the performance of DBT to mammography after initiation or completion of NAC. FDG-PET/CT Skull Base to Mid-Thigh Because of its relatively low specificity, PET/CT is not routinely used for posttreatment imaging of the primary breast tumor and is typically only used in combination with other imaging modalities to monitor treatment response [52-54]. Two meta-analyses found posttreatment PET/CT sensitivities of 77% to 84% and specificities of 66% to 78% for predicting response to therapy [52,54]. In a study by Bassa et al [55], PET was able to accurately predict residual disease in only 75% of cases, compared with 88% for US. However, PET may have use in assessing early response to therapy, with a study in 47 patients showing that a >50% to 60% reduction in FDG uptake after one cycle of therapy correlated with a pCR [56]. PET imaging may be more helpful for certain tumor subtypes. Three studies showed that PET/CT can reliably detect early response and predict residual disease in HER2/neu-positive tumors [57-59], and a <42% decrease in radioisotope uptake in triple-negative tumors correlates with poor response and outcome [60]. Lobular cancers are less FDG avid, making assessment challenging [61,62]. Mammography Diagnostic Although mammography and US are reliable for determining tumor size at diagnosis [11-15], changes within the tumor, secondary to NAC, may be difficult to evaluate after treatment is initiated. It is well known that tumoral changes related to necrosis, fragmentation, and fibrosis make it difficult for mammography, DBT, and US to accurately determine residual tumor burden [43,44]. In a retrospective study of 445 patients who underwent NAC, mammography was 94% sensitive and 50% specific for predicting residual disease in the breast. In cases presenting as mass lesions, most masses (95%) decreased in mammographic size with treatment.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. There is no relevant literature specifically comparing the performance of DBT to mammography after initiation or completion of NAC. FDG-PET/CT Skull Base to Mid-Thigh Because of its relatively low specificity, PET/CT is not routinely used for posttreatment imaging of the primary breast tumor and is typically only used in combination with other imaging modalities to monitor treatment response [52-54]. Two meta-analyses found posttreatment PET/CT sensitivities of 77% to 84% and specificities of 66% to 78% for predicting response to therapy [52,54]. In a study by Bassa et al [55], PET was able to accurately predict residual disease in only 75% of cases, compared with 88% for US. However, PET may have use in assessing early response to therapy, with a study in 47 patients showing that a >50% to 60% reduction in FDG uptake after one cycle of therapy correlated with a pCR [56]. PET imaging may be more helpful for certain tumor subtypes. Three studies showed that PET/CT can reliably detect early response and predict residual disease in HER2/neu-positive tumors [57-59], and a <42% decrease in radioisotope uptake in triple-negative tumors correlates with poor response and outcome [60]. Lobular cancers are less FDG avid, making assessment challenging [61,62]. Mammography Diagnostic Although mammography and US are reliable for determining tumor size at diagnosis [11-15], changes within the tumor, secondary to NAC, may be difficult to evaluate after treatment is initiated. It is well known that tumoral changes related to necrosis, fragmentation, and fibrosis make it difficult for mammography, DBT, and US to accurately determine residual tumor burden [43,44]. In a retrospective study of 445 patients who underwent NAC, mammography was 94% sensitive and 50% specific for predicting residual disease in the breast. In cases presenting as mass lesions, most masses (95%) decreased in mammographic size with treatment.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

However, there was correlation between mammographic size and surgical pathology in only 60% of cases [45]. One study found that if >50% of the margin of the primary lesion was mammographically visible at baseline, posttreatment mammographic imaging was a reliable tool for determining lesion size [28,46]. In a study of 56 patients, mammography was 79% sensitive and 77% specific in predicting residual disease after therapy, performing better than clinical breast examination [47]. The extent of calcifications on mammography after therapy does not correlate well with residual tumor burden and is overestimated in up to 45% of patients [48-50]. Therefore, it is not a reliable marker of remaining viable tumor. In a study including 139 patients with baseline mammographic calcifications, residual calcifications were present 7 Monitoring Response to Neoadjuvant Chemotherapy on all posttreatment mammograms [45]. ER-positive tumors are more likely than ER-negative tumors to have residual malignant calcifications on mammography after treatment, whereas triple-negative tumors are the least likely to have residual malignant calcifications after therapy, suggesting that different tumor subtypes may warrant different approaches [48,51]. There is no relevant literature specifically comparing the performance of DBT to mammography after initiation of completion of NAC. MRI Breast Without and With IV Contrast MRI is a functional imaging technique that permits evaluation of a viable tumor before and after NAC by detecting changes in tumor vascularity [31]. There is substantial evidence to support the routine use of MRI to stage, monitor early response, and assess for residual and recurrent disease, given the overall high sensitivity and relatively high specificity of this technique [1]. However, MRI can overestimate as well as underestimate the amount of residual tumor after completion of therapy.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. However, there was correlation between mammographic size and surgical pathology in only 60% of cases [45]. One study found that if >50% of the margin of the primary lesion was mammographically visible at baseline, posttreatment mammographic imaging was a reliable tool for determining lesion size [28,46]. In a study of 56 patients, mammography was 79% sensitive and 77% specific in predicting residual disease after therapy, performing better than clinical breast examination [47]. The extent of calcifications on mammography after therapy does not correlate well with residual tumor burden and is overestimated in up to 45% of patients [48-50]. Therefore, it is not a reliable marker of remaining viable tumor. In a study including 139 patients with baseline mammographic calcifications, residual calcifications were present 7 Monitoring Response to Neoadjuvant Chemotherapy on all posttreatment mammograms [45]. ER-positive tumors are more likely than ER-negative tumors to have residual malignant calcifications on mammography after treatment, whereas triple-negative tumors are the least likely to have residual malignant calcifications after therapy, suggesting that different tumor subtypes may warrant different approaches [48,51]. There is no relevant literature specifically comparing the performance of DBT to mammography after initiation of completion of NAC. MRI Breast Without and With IV Contrast MRI is a functional imaging technique that permits evaluation of a viable tumor before and after NAC by detecting changes in tumor vascularity [31]. There is substantial evidence to support the routine use of MRI to stage, monitor early response, and assess for residual and recurrent disease, given the overall high sensitivity and relatively high specificity of this technique [1]. However, MRI can overestimate as well as underestimate the amount of residual tumor after completion of therapy.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Multiple studies show that dynamic contrast-enhanced MRI is the optimal imaging tool to determine disease response, with sensitivity approaching 90%, specificity ranging from 60 to 100%, and an accuracy of approximately 91% [31,32,35,36,43,63-66]. MRI is particularly helpful in patients with documented multifocal and multicentric tumors on the pretreatment study, despite the fact that MRI underestimates disease extent in up to 18% of cases [67,68]. However, there is a lack of consensus in the literature on the optimal imaging interval to assess response to therapy. Tumor measurements on MRI more accurately predict residual tumor and pathologic response than clinical assessment, a finding corroborated in several studies [69-71], with volume measurements performing better than tumor diameter early in treatment after the first cycle of chemotherapy [31]. In a prospective clinical trial of 138 patients, longest diameter on posttreatment MRI was superior to both mammography and clinical breast examination in detecting residual disease. MRI tumor volume was also shown to predict recurrence free survival in a trial of 162 patients [72]. The ability of MRI to evaluate disease response is variable on the basis of tumor subtype, being more effective for invasive lobular carcinoma, triple-negative, and HER2/neu-positive tumors and less accurate for luminal subtypes (ER and/or progesterone receptor positive, HER2/neu-positive or negative), with an overall accuracy of approximately 75% [73-81]. A study of 208 patients suggested that patients who can safely consider breast conservation therapy after NAC have tumors <3 cm in maximal size on pretreatment MRI, reduction in tumor size on posttreatment MRI, and more often have HER2/neu-positive or triple-negative tumors [67,82]. When the tumor presents as diffuse nonmass enhancement on the pretreatment MRI or is of low nuclear grade, MRI is less helpful in assessing response to therapy [83].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Multiple studies show that dynamic contrast-enhanced MRI is the optimal imaging tool to determine disease response, with sensitivity approaching 90%, specificity ranging from 60 to 100%, and an accuracy of approximately 91% [31,32,35,36,43,63-66]. MRI is particularly helpful in patients with documented multifocal and multicentric tumors on the pretreatment study, despite the fact that MRI underestimates disease extent in up to 18% of cases [67,68]. However, there is a lack of consensus in the literature on the optimal imaging interval to assess response to therapy. Tumor measurements on MRI more accurately predict residual tumor and pathologic response than clinical assessment, a finding corroborated in several studies [69-71], with volume measurements performing better than tumor diameter early in treatment after the first cycle of chemotherapy [31]. In a prospective clinical trial of 138 patients, longest diameter on posttreatment MRI was superior to both mammography and clinical breast examination in detecting residual disease. MRI tumor volume was also shown to predict recurrence free survival in a trial of 162 patients [72]. The ability of MRI to evaluate disease response is variable on the basis of tumor subtype, being more effective for invasive lobular carcinoma, triple-negative, and HER2/neu-positive tumors and less accurate for luminal subtypes (ER and/or progesterone receptor positive, HER2/neu-positive or negative), with an overall accuracy of approximately 75% [73-81]. A study of 208 patients suggested that patients who can safely consider breast conservation therapy after NAC have tumors <3 cm in maximal size on pretreatment MRI, reduction in tumor size on posttreatment MRI, and more often have HER2/neu-positive or triple-negative tumors [67,82]. When the tumor presents as diffuse nonmass enhancement on the pretreatment MRI or is of low nuclear grade, MRI is less helpful in assessing response to therapy [83].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

In addition, tumors presenting initially as nonmass enhancement more likely presented as scattered foci within an area of fibrosis on posttreatment MRI, making prediction of residual disease challenging [34,84]. Finally, there is some evidence that certain chemotherapeutic agents, such as ER modulators, antiangiogenic agents, and taxane-based therapies, may alter perfusion to the breasts, limiting the ability of MRI to accurately predict residual tumor after chemotherapy, most often leading to disease underestimation [85,86]. MRI Breast Without IV Contrast A small study of 71 patients with MRI before and after treatment found no significant difference in lesion size interpretation on unenhanced versus enhanced MRI sequences [39]. However, there is insufficient literature to support the use of MRI without IV contrast of the breast in initial imaging evaluation of tumor size and extent in the breast after initiation or completion of chemotherapy. Sestamibi MBI In a study of 20 patients who underwent imaging with Tc-99m sestamibi, reduction in tumor size correlated reliably with size on MRI, but tumor to background ratio after chemotherapy did not correlate with treatment response [95]. Monitoring Response to Neoadjuvant Chemotherapy A small study of 62 patients also showed that high uptake after chemotherapy predicts poor survival [96]. In one study of 122 patients, breast-specific gamma imaging had sensitivity of 74% and specificity of 72% for detection of residual tumor after chemotherapy, but it underestimated the amount of residual disease for tumors of luminal subtype [97]. In a small study of 49 patients with locally advanced breast cancer, MBI did not accurately predict response to therapy [98]. In a prospective study of 90 patients, posttreatment MBI had a higher false-negative rate than MRI (41% versus 18%) for predicting pathologic response [41].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. In addition, tumors presenting initially as nonmass enhancement more likely presented as scattered foci within an area of fibrosis on posttreatment MRI, making prediction of residual disease challenging [34,84]. Finally, there is some evidence that certain chemotherapeutic agents, such as ER modulators, antiangiogenic agents, and taxane-based therapies, may alter perfusion to the breasts, limiting the ability of MRI to accurately predict residual tumor after chemotherapy, most often leading to disease underestimation [85,86]. MRI Breast Without IV Contrast A small study of 71 patients with MRI before and after treatment found no significant difference in lesion size interpretation on unenhanced versus enhanced MRI sequences [39]. However, there is insufficient literature to support the use of MRI without IV contrast of the breast in initial imaging evaluation of tumor size and extent in the breast after initiation or completion of chemotherapy. Sestamibi MBI In a study of 20 patients who underwent imaging with Tc-99m sestamibi, reduction in tumor size correlated reliably with size on MRI, but tumor to background ratio after chemotherapy did not correlate with treatment response [95]. Monitoring Response to Neoadjuvant Chemotherapy A small study of 62 patients also showed that high uptake after chemotherapy predicts poor survival [96]. In one study of 122 patients, breast-specific gamma imaging had sensitivity of 74% and specificity of 72% for detection of residual tumor after chemotherapy, but it underestimated the amount of residual disease for tumors of luminal subtype [97]. In a small study of 49 patients with locally advanced breast cancer, MBI did not accurately predict response to therapy [98]. In a prospective study of 90 patients, posttreatment MBI had a higher false-negative rate than MRI (41% versus 18%) for predicting pathologic response [41].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

A retrospective study of 114 patients demonstrated that posttreatment MBI had a lower sensitivity than MRI for detecting residual tumor (70% versus 83%). However, MBI was more specific than MRI in determining CR (90% versus 60%) [99]. At present, there is insufficient literature to support the routine use of Sestamibi MBI in imaging of the breast after initiation or completion of NAC. US Breast US is a reliable modality for determining tumor size, especially if the residual tumor measures >7 mm [100,101]. A decrease in tumor vascularity does appear to correlate with response [28]. In 2 studies, US predicted residual tumor size accurately in 60% to 80% of patients, compared with 32% to 71% for mammography [102,103]. In a study by Keune et al [104], the absence of residual disease on both mammography and US correlated with a pCR in 80% of patients. Although pretreatment tumor stiffness as determined by shear-wave elastography has shown strong correlation with response to therapy, there is insufficient data to support its routine use at this time [105,106]. In addition, there is insufficient data to support the routine use of contrast-enhanced US, although some early research suggests that changes in the time-intensity curves may reliably predict response to therapy [107,108]. Variant 3: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer, clinically node-negative. Axillary evaluation prior to neoadjuvant chemotherapy. Initial imaging. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in the initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. A retrospective study of 114 patients demonstrated that posttreatment MBI had a lower sensitivity than MRI for detecting residual tumor (70% versus 83%). However, MBI was more specific than MRI in determining CR (90% versus 60%) [99]. At present, there is insufficient literature to support the routine use of Sestamibi MBI in imaging of the breast after initiation or completion of NAC. US Breast US is a reliable modality for determining tumor size, especially if the residual tumor measures >7 mm [100,101]. A decrease in tumor vascularity does appear to correlate with response [28]. In 2 studies, US predicted residual tumor size accurately in 60% to 80% of patients, compared with 32% to 71% for mammography [102,103]. In a study by Keune et al [104], the absence of residual disease on both mammography and US correlated with a pCR in 80% of patients. Although pretreatment tumor stiffness as determined by shear-wave elastography has shown strong correlation with response to therapy, there is insufficient data to support its routine use at this time [105,106]. In addition, there is insufficient data to support the routine use of contrast-enhanced US, although some early research suggests that changes in the time-intensity curves may reliably predict response to therapy [107,108]. Variant 3: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer, clinically node-negative. Axillary evaluation prior to neoadjuvant chemotherapy. Initial imaging. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in the initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is not routinely used for initial imaging of the clinically node-negative axilla before NAC because of its low sensitivity and specificity for detecting nodal disease [4]. In several studies on detection of nodal disease, including a multicenter study of 360 patients, PET had disparate sensitivities (43%-79%) and specificities (66%-93%), possibly related to differences in tumor size in patient populations [109,110]. Given these limitations, surgical sampling of the axillary nodes remains the standard of care. However, when an FDG-avid axillary node is seen on a pretreatment PET/CT scan, this is highly predictive of metastasis [111]. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast There is robust evidence to support MRI for determining the extent of disease in the breast, both before and after NAC [1,4,31,32,35,36,43,63-66]. Although the axillary lymph nodes are included on MRI, it is only moderately sensitive for the detection of axillary nodal metastasis before and after therapy [4,112,113]. Therefore, MRI is not typically obtained solely for the purpose of staging the clinically node-negative axilla before NAC [4]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in initial imaging evaluation of the axilla before NAC. US Axilla Current National Comprehensive Cancer Network practice guidelines recommend considering axillary US and possible biopsy before starting NAC, even in clinically node-negative patients [115,116].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is not routinely used for initial imaging of the clinically node-negative axilla before NAC because of its low sensitivity and specificity for detecting nodal disease [4]. In several studies on detection of nodal disease, including a multicenter study of 360 patients, PET had disparate sensitivities (43%-79%) and specificities (66%-93%), possibly related to differences in tumor size in patient populations [109,110]. Given these limitations, surgical sampling of the axillary nodes remains the standard of care. However, when an FDG-avid axillary node is seen on a pretreatment PET/CT scan, this is highly predictive of metastasis [111]. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast There is robust evidence to support MRI for determining the extent of disease in the breast, both before and after NAC [1,4,31,32,35,36,43,63-66]. Although the axillary lymph nodes are included on MRI, it is only moderately sensitive for the detection of axillary nodal metastasis before and after therapy [4,112,113]. Therefore, MRI is not typically obtained solely for the purpose of staging the clinically node-negative axilla before NAC [4]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in initial imaging evaluation of the axilla before NAC. US Axilla Current National Comprehensive Cancer Network practice guidelines recommend considering axillary US and possible biopsy before starting NAC, even in clinically node-negative patients [115,116].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Assessment of the axilla before and after NAC with US can help guide surgical management. US permits routine visualization of stage I and II nodes. By identifying subclinical metastases in clinically node-negative patients, US-guided fine-needle aspiration (FNA) or core needle biopsy (CNB) may select patients who require axillary lymph node dissection [116]. However, a study of 402 patients with a clinically negative axilla demonstrated that half of patients with abnormal lymph nodes on pretreatment imaging did not require axillary lymph node dissection [116]. Therefore, pretreatment imaging of the axilla in clinically node-negative patients remains controversial [4]. US-Guided Core Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation. However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease. Overall, US-guided biopsy offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation. However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Assessment of the axilla before and after NAC with US can help guide surgical management. US permits routine visualization of stage I and II nodes. By identifying subclinical metastases in clinically node-negative patients, US-guided fine-needle aspiration (FNA) or core needle biopsy (CNB) may select patients who require axillary lymph node dissection [116]. However, a study of 402 patients with a clinically negative axilla demonstrated that half of patients with abnormal lymph nodes on pretreatment imaging did not require axillary lymph node dissection [116]. Therefore, pretreatment imaging of the axilla in clinically node-negative patients remains controversial [4]. US-Guided Core Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation. However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease. Overall, US-guided biopsy offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation. However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease.

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acrac_3099208_15

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Overall, US-guided FNA offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. Variant 4: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer, clinically node-positive. Axillary evaluation prior to neoadjuvant chemotherapy. Initial imaging. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in the initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT may be useful for staging and restaging clinically node-positive patients undergoing NAC [4]. In node-positive patients, the decrease in standardize uptake value from pre- to posttreatment scans can be used to monitor response and help predict pCR [116]. This possibly may lead to less aggressive axillary surgery upon completion of chemotherapy rather than complete lymph node dissection [118]. In several studies on detection of nodal disease, including a multicenter study of 360 patients, PET had disparate sensitivities (43%-79%) and specificities (66%-93%), possibly related to differences in tumor size in patient populations [109,110]. Given these limitations, surgical sampling of the axillary nodes remains the standard of care.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Overall, US-guided FNA offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. Variant 4: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer, clinically node-positive. Axillary evaluation prior to neoadjuvant chemotherapy. Initial imaging. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in the initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT may be useful for staging and restaging clinically node-positive patients undergoing NAC [4]. In node-positive patients, the decrease in standardize uptake value from pre- to posttreatment scans can be used to monitor response and help predict pCR [116]. This possibly may lead to less aggressive axillary surgery upon completion of chemotherapy rather than complete lymph node dissection [118]. In several studies on detection of nodal disease, including a multicenter study of 360 patients, PET had disparate sensitivities (43%-79%) and specificities (66%-93%), possibly related to differences in tumor size in patient populations [109,110]. Given these limitations, surgical sampling of the axillary nodes remains the standard of care.

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acrac_3099208_16

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

However, when an FDG-avid axillary node is seen on a pretreatment PET/CT scan, this is highly predictive of metastasis [111]. Monitoring Response to Neoadjuvant Chemotherapy Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast MRI does not always include the entire axilla and is not routinely used solely for evaluation of axillary lymph nodes. However, contrast-enhanced MRI may be useful for monitoring the breast and axillary response in clinically node- positive patients [4]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in initial imaging evaluation of the axilla before NAC. US Axilla Axillary US is routinely performed for pretreatment evaluation of a clinically positive axilla [4]. Current National Comprehensive Cancer Network practice guidelines recommend axillary US and possible biopsy before starting systemic therapy [115]. US-guided FNA or CNB can confirm and mark metastatic disease. When US-guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy because the completion of axillary surgery is typically performed after therapy [2,117]. Placing a biopsy clip to mark the metastatic lymph node before therapy can also help guide the type of axillary restaging surgery following NAC [119]. US-Guided Core Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. However, when an FDG-avid axillary node is seen on a pretreatment PET/CT scan, this is highly predictive of metastasis [111]. Monitoring Response to Neoadjuvant Chemotherapy Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging evaluation of the axilla before NAC. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast MRI does not always include the entire axilla and is not routinely used solely for evaluation of axillary lymph nodes. However, contrast-enhanced MRI may be useful for monitoring the breast and axillary response in clinically node- positive patients [4]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in initial imaging evaluation of the axilla before NAC. US Axilla Axillary US is routinely performed for pretreatment evaluation of a clinically positive axilla [4]. Current National Comprehensive Cancer Network practice guidelines recommend axillary US and possible biopsy before starting systemic therapy [115]. US-guided FNA or CNB can confirm and mark metastatic disease. When US-guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy because the completion of axillary surgery is typically performed after therapy [2,117]. Placing a biopsy clip to mark the metastatic lymph node before therapy can also help guide the type of axillary restaging surgery following NAC [119]. US-Guided Core Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation.

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acrac_3099208_17

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease. Overall, US-guided biopsy offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation. However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease. Overall, US-guided FNA offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. Variant 5: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer, clinically node-negative. Axillary evaluation after completion of neoadjuvant chemotherapy, axilla not previously evaluated. Initial imaging. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in initial imaging of the axilla after NAC [4].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease. Overall, US-guided biopsy offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no evidence to support US-guided sampling as the initial imaging test for axillary lymph node evaluation. However, US-guided axillary lymph node sampling is typically the next study performed when axillary imaging is suspicious for metastatic disease. Overall, US-guided FNA offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US- guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy, because the completion of axillary surgery is typically performed after therapy [2,117]. Variant 5: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer, clinically node-negative. Axillary evaluation after completion of neoadjuvant chemotherapy, axilla not previously evaluated. Initial imaging. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in initial imaging of the axilla after NAC [4].

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acrac_3099208_18

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Monitoring Response to Neoadjuvant Chemotherapy Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. FDG-PET/CT Skull Base to Mid-Thigh PET/CT is not routinely used for evaluation of the axilla after NAC as data are limited [4]. In several studies on detection of nodal disease, including a multicenter study of 360 patients, PET had disparate sensitivities (43%-79%) and specificities (66%-93%), possibly related to differences in tumor size in patient populations [109,110]. Given these limitations, this modality is not particularly useful to evaluate the axilla, and surgical sampling of the axillary nodes remains the standard of care. However, when an FDG-avid axillary node is seen on a pretreatment PET/CT scan, this is highly predictive of metastasis [111]. In addition, in node-positive tumors, PET/CT can be used to monitor response and possibly lead to sentinel node biopsy upon completion of chemotherapy rather than full axillary dissection [118]. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging of the axilla after NAC [4]. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast The current literature evaluates performance of posttreatment MRI evaluation of the axilla only in the setting of baseline pretreatment imaging and/or clinically node-positive patients, as described below. These data cannot necessarily be extrapolated to initial imaging after completion of therapy in the absence of pretreatment axillary evaluation.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Monitoring Response to Neoadjuvant Chemotherapy Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. FDG-PET/CT Skull Base to Mid-Thigh PET/CT is not routinely used for evaluation of the axilla after NAC as data are limited [4]. In several studies on detection of nodal disease, including a multicenter study of 360 patients, PET had disparate sensitivities (43%-79%) and specificities (66%-93%), possibly related to differences in tumor size in patient populations [109,110]. Given these limitations, this modality is not particularly useful to evaluate the axilla, and surgical sampling of the axillary nodes remains the standard of care. However, when an FDG-avid axillary node is seen on a pretreatment PET/CT scan, this is highly predictive of metastasis [111]. In addition, in node-positive tumors, PET/CT can be used to monitor response and possibly lead to sentinel node biopsy upon completion of chemotherapy rather than full axillary dissection [118]. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging of the axilla after NAC [4]. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast The current literature evaluates performance of posttreatment MRI evaluation of the axilla only in the setting of baseline pretreatment imaging and/or clinically node-positive patients, as described below. These data cannot necessarily be extrapolated to initial imaging after completion of therapy in the absence of pretreatment axillary evaluation.

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acrac_3099208_19

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

MRI of the axilla is only 38% to 61% sensitive for detection of residual disease after NAC [112,113]; therefore, surgical sampling is the standard of care [114,120-122]. In a retrospective study of 135 clinically node-positive patients after NAC, MRI had a low negative predictive value (NPV) of 26% for predicting axillary disease when a positive MRI was defined by node >1 cm, cortex >3 mm, loss of hilum, or irregular contour [121]. In a retrospective study of 269 node-positive patients, posttreatment MRI was only 38% sensitive, 76% specific, and 58% accurate in predicting the pathology of the sentinel lymph node (SLN). In a prospective study of 45 patients, 35 of whom were node-positive, there was no association between posttreatment axillary MRI and surgical pathology; MRI had a high false negative rate (46%), low sensitivity (55%), and specificity (63%) [114]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in initial imaging of the axilla after NAC. US Axilla US is not typically performed for initial evaluation of the axilla after initiation of NAC, and the current literature does not specifically evaluate this scenario. The literature on posttreatment axillary US predicting residual nodal disease evaluates patients with established node-positive disease before therapy, as described below. These data cannot necessarily be extrapolated to initial imaging after therapy in the absence of pretreatment axillary evaluation. No imaging test can reliably detect residual nodal disease after NAC, and therefore surgical sampling is the standard of care. In established node-positive patients after therapy, axillary US only demonstrates moderate sensitivity (53%-86%) and specificity (78%) for detecting residual disease with an NPV ranging from 46% to 90% [112,123,124]. Therefore, surgical sampling of axillary lymph nodes after therapy remains the standard of care.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. MRI of the axilla is only 38% to 61% sensitive for detection of residual disease after NAC [112,113]; therefore, surgical sampling is the standard of care [114,120-122]. In a retrospective study of 135 clinically node-positive patients after NAC, MRI had a low negative predictive value (NPV) of 26% for predicting axillary disease when a positive MRI was defined by node >1 cm, cortex >3 mm, loss of hilum, or irregular contour [121]. In a retrospective study of 269 node-positive patients, posttreatment MRI was only 38% sensitive, 76% specific, and 58% accurate in predicting the pathology of the sentinel lymph node (SLN). In a prospective study of 45 patients, 35 of whom were node-positive, there was no association between posttreatment axillary MRI and surgical pathology; MRI had a high false negative rate (46%), low sensitivity (55%), and specificity (63%) [114]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in initial imaging of the axilla after NAC. US Axilla US is not typically performed for initial evaluation of the axilla after initiation of NAC, and the current literature does not specifically evaluate this scenario. The literature on posttreatment axillary US predicting residual nodal disease evaluates patients with established node-positive disease before therapy, as described below. These data cannot necessarily be extrapolated to initial imaging after therapy in the absence of pretreatment axillary evaluation. No imaging test can reliably detect residual nodal disease after NAC, and therefore surgical sampling is the standard of care. In established node-positive patients after therapy, axillary US only demonstrates moderate sensitivity (53%-86%) and specificity (78%) for detecting residual disease with an NPV ranging from 46% to 90% [112,123,124]. Therefore, surgical sampling of axillary lymph nodes after therapy remains the standard of care.

3099208

acrac_3099208_20

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

In a retrospective study of 408 clinically node-positive breast cancer patients treated with NAC, the strongest predictor for residual axillary disease was preoperative US showing axillary lymphadenopathy, defined as axial cortical thickness >3.5 mm or loss of the hilum [125]. The prospective clinical Z1071 trial included 611 patients with US after NAC; US features associated with residual disease included increased cortical thickness (mean 3.5 mm), absent hilum, and longer lymph node diameter [126]. Monitoring Response to Neoadjuvant Chemotherapy US-Guided Core Biopsy Axillary Node There is no relevant literature to support the use of US-guided core biopsy of axillary nodes in initial imaging of the axilla after completion of NAC. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no relevant literature to support the use of US-guided FNA of axillary nodes in initial imaging of the axilla after completion of NAC. Variant 6: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer with clinical suspicion of metastatic disease. Staging or assessment of response to neoadjuvant chemotherapy. Initial imaging. Bone Scan Whole Body Staging of patients before and after treatment typically entails either 1) FDG-PET/CT skull base to mid-thigh only or 2) bone scan in conjunction with CT chest, abdomen, and pelvis with IV contrast, depending upon institutional preference. There is no evidence to support performing all 3 studies. Bone scan represents one of the standard imaging tests to stage a patient with newly diagnosed breast cancer, allowing assessment of bony metastasis. PET/CT combines cross-sectional imaging with tumor metabolism and has been shown to be more sensitive and accurate than conventional staging with combined CT and bone scan [127].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. In a retrospective study of 408 clinically node-positive breast cancer patients treated with NAC, the strongest predictor for residual axillary disease was preoperative US showing axillary lymphadenopathy, defined as axial cortical thickness >3.5 mm or loss of the hilum [125]. The prospective clinical Z1071 trial included 611 patients with US after NAC; US features associated with residual disease included increased cortical thickness (mean 3.5 mm), absent hilum, and longer lymph node diameter [126]. Monitoring Response to Neoadjuvant Chemotherapy US-Guided Core Biopsy Axillary Node There is no relevant literature to support the use of US-guided core biopsy of axillary nodes in initial imaging of the axilla after completion of NAC. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no relevant literature to support the use of US-guided FNA of axillary nodes in initial imaging of the axilla after completion of NAC. Variant 6: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer with clinical suspicion of metastatic disease. Staging or assessment of response to neoadjuvant chemotherapy. Initial imaging. Bone Scan Whole Body Staging of patients before and after treatment typically entails either 1) FDG-PET/CT skull base to mid-thigh only or 2) bone scan in conjunction with CT chest, abdomen, and pelvis with IV contrast, depending upon institutional preference. There is no evidence to support performing all 3 studies. Bone scan represents one of the standard imaging tests to stage a patient with newly diagnosed breast cancer, allowing assessment of bony metastasis. PET/CT combines cross-sectional imaging with tumor metabolism and has been shown to be more sensitive and accurate than conventional staging with combined CT and bone scan [127].

3099208

acrac_3099208_21

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

CT Chest, Abdomen, and Pelvis With IV Contrast Staging of patients before and after treatment typically entails either 1) FDG-PET/CT skull base to mid-thigh only or 2) bone scan in conjunction with CT chest, abdomen, and pelvis with IV contrast, depending upon institutional preference. There is no evidence to support performing all 3 studies. CT with IV contrast is commonly used to stage patients with newly diagnosed, locally advanced, or recurrent breast cancer [128]. PET/CT combines cross-sectional imaging with tumor metabolism and has been shown to be more sensitive and accurate than conventional staging with combined CT and bone scan [127]. CT Chest, Abdomen, and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT chest, abdomen, and pelvis without and with IV contrast in the initial evaluation of metastatic disease. CT Chest, Abdomen, and Pelvis Without IV Contrast There is no relevant literature to support the use of CT chest, abdomen, and pelvis without IV contrast in the initial evaluation of metastatic disease. FDG-PET/CT Skull Base to Mid-Thigh Staging of patients before and after treatment typically entails either 1) FDG-PET/CT skull base to mid-thigh only or 2) bone scan in conjunction with CT chest, abdomen, and pelvis with IV contrast, depending upon institutional preference. There is no evidence to support performing all 3 studies. PET/CT combines cross-sectional imaging with tumor metabolism and has been shown to be more sensitive and accurate than conventional staging with combined CT and bone scan [127]. Staging with PET/CT detects distant metastases with a sensitivity of 50% to 100% and a specificity of 50% to 97% in patients with advanced breast cancers, some of which were occult on conventional CT imaging. In one study by Lee et al, the detection of distant metastases occult on conventional CT imaging led to changes in clinical stage for 52% of women [129].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. CT Chest, Abdomen, and Pelvis With IV Contrast Staging of patients before and after treatment typically entails either 1) FDG-PET/CT skull base to mid-thigh only or 2) bone scan in conjunction with CT chest, abdomen, and pelvis with IV contrast, depending upon institutional preference. There is no evidence to support performing all 3 studies. CT with IV contrast is commonly used to stage patients with newly diagnosed, locally advanced, or recurrent breast cancer [128]. PET/CT combines cross-sectional imaging with tumor metabolism and has been shown to be more sensitive and accurate than conventional staging with combined CT and bone scan [127]. CT Chest, Abdomen, and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT chest, abdomen, and pelvis without and with IV contrast in the initial evaluation of metastatic disease. CT Chest, Abdomen, and Pelvis Without IV Contrast There is no relevant literature to support the use of CT chest, abdomen, and pelvis without IV contrast in the initial evaluation of metastatic disease. FDG-PET/CT Skull Base to Mid-Thigh Staging of patients before and after treatment typically entails either 1) FDG-PET/CT skull base to mid-thigh only or 2) bone scan in conjunction with CT chest, abdomen, and pelvis with IV contrast, depending upon institutional preference. There is no evidence to support performing all 3 studies. PET/CT combines cross-sectional imaging with tumor metabolism and has been shown to be more sensitive and accurate than conventional staging with combined CT and bone scan [127]. Staging with PET/CT detects distant metastases with a sensitivity of 50% to 100% and a specificity of 50% to 97% in patients with advanced breast cancers, some of which were occult on conventional CT imaging. In one study by Lee et al, the detection of distant metastases occult on conventional CT imaging led to changes in clinical stage for 52% of women [129].

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acrac_3099208_22

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Given that 8% to 14% of women with locally advanced breast cancer have distant metastatic disease at diagnosis (beyond the axillary nodes), FDG-PET/CT skull base to mid-thigh may be preferred over conventional CT imaging [130]. In addition, several studies have shown FDG-PET/CT to be superior in detecting internal mammary and mediastinal lymphadenopathy [129] but inferior to contrast-enhanced chest CT at detecting pulmonary metastases [130]. Multiple studies show that PET/CT staging is more useful for stage IIIB and operable stage IIIA tumors and specific tumor subtypes including invasive ductal cancers, ER-negative and triple-negative tumors, high-grade malignancies, and those with p53 mutations [131-133]. PET/CT staging is not as useful for low-grade malignancies or invasive lobular cancers because of the overall low isotope uptake [134]. MRI Chest, Abdomen, Pelvis Without and With IV Contrast There is no relevant literature to support the use of MRI chest, abdomen, and pelvis without and with IV contrast in the initial evaluation of metastatic disease. 13 Monitoring Response to Neoadjuvant Chemotherapy MRI Chest, Abdomen, Pelvis Without IV Contrast There is no relevant literature to support the use of MRI chest, abdomen, and pelvis without IV contrast in the initial evaluation of metastatic disease. Variant 7: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known axillary lymph node-positive breast cancer on prior mammography, US, or MRI. Axillary evaluation after completion of neoadjuvant chemotherapy, axilla previously evaluated. Next imaging study. Digital Breast Tomosynthesis Diagnostic Although many patients undergo mammography or DBT after NAC, there is no specific evidence supporting its use in the imaging of known axillary lymph node-positive breast cancer after completion of therapy.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Given that 8% to 14% of women with locally advanced breast cancer have distant metastatic disease at diagnosis (beyond the axillary nodes), FDG-PET/CT skull base to mid-thigh may be preferred over conventional CT imaging [130]. In addition, several studies have shown FDG-PET/CT to be superior in detecting internal mammary and mediastinal lymphadenopathy [129] but inferior to contrast-enhanced chest CT at detecting pulmonary metastases [130]. Multiple studies show that PET/CT staging is more useful for stage IIIB and operable stage IIIA tumors and specific tumor subtypes including invasive ductal cancers, ER-negative and triple-negative tumors, high-grade malignancies, and those with p53 mutations [131-133]. PET/CT staging is not as useful for low-grade malignancies or invasive lobular cancers because of the overall low isotope uptake [134]. MRI Chest, Abdomen, Pelvis Without and With IV Contrast There is no relevant literature to support the use of MRI chest, abdomen, and pelvis without and with IV contrast in the initial evaluation of metastatic disease. 13 Monitoring Response to Neoadjuvant Chemotherapy MRI Chest, Abdomen, Pelvis Without IV Contrast There is no relevant literature to support the use of MRI chest, abdomen, and pelvis without IV contrast in the initial evaluation of metastatic disease. Variant 7: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known axillary lymph node-positive breast cancer on prior mammography, US, or MRI. Axillary evaluation after completion of neoadjuvant chemotherapy, axilla previously evaluated. Next imaging study. Digital Breast Tomosynthesis Diagnostic Although many patients undergo mammography or DBT after NAC, there is no specific evidence supporting its use in the imaging of known axillary lymph node-positive breast cancer after completion of therapy.

3099208

acrac_3099208_23

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

The axilla is incompletely visualized on the mediolateral and lateral projections, thereby limiting the use of these modalities to reliably detect residual disease. FDG-PET/CT Skull Base to Mid-Thigh PET/CT is not routinely used to evaluate the axilla after completion of NAC. Although a few studies suggest that PET can reliably predict the response of axillary nodes early in treatment, a majority of studies show that PET has low sensitivity (63%) for detection of residual disease after NAC [112,135]. No imaging test can reliably detect residual nodal disease after NAC, and therefore surgical sampling is the standard of care. Mammography Diagnostic Although many patients undergo mammography or DBT after NAC, there is no specific evidence supporting its use in the imaging of known axillary lymph node-positive breast cancer after completion of therapy [4]. The axilla is incompletely visualized on the mediolateral and lateral projections, thereby limiting the use of these modalities to reliably detect residual disease. MRI Breast Without and With IV Contrast MRI is not routinely used for evaluation of the axilla after completion of NAC because it is only 38% to 61% sensitive for detecting residual axillary disease [112-114,120-122]. No imaging test can reliably detect residual nodal disease after NAC, and therefore surgical sampling is the standard of care. Use of MRI for restaging the axilla in clinically node-positive patients is questionable [4]. In a retrospective study of 135 clinically node-positive patients who underwent NAC, MRI evaluation of the axilla after treatment had a low NPV (26%) and therefore could not predict residual axillary disease when a positive MRI of the axilla was defined as node >1 cm, cortex >3 mm, loss of hilum, or irregular contour [121]. In a retrospective study of 269 node-positive patients, postchemotherapy MRI was only 38% sensitive, 76% specific, and 58% accurate in predicting the pathology result of the SLN.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. The axilla is incompletely visualized on the mediolateral and lateral projections, thereby limiting the use of these modalities to reliably detect residual disease. FDG-PET/CT Skull Base to Mid-Thigh PET/CT is not routinely used to evaluate the axilla after completion of NAC. Although a few studies suggest that PET can reliably predict the response of axillary nodes early in treatment, a majority of studies show that PET has low sensitivity (63%) for detection of residual disease after NAC [112,135]. No imaging test can reliably detect residual nodal disease after NAC, and therefore surgical sampling is the standard of care. Mammography Diagnostic Although many patients undergo mammography or DBT after NAC, there is no specific evidence supporting its use in the imaging of known axillary lymph node-positive breast cancer after completion of therapy [4]. The axilla is incompletely visualized on the mediolateral and lateral projections, thereby limiting the use of these modalities to reliably detect residual disease. MRI Breast Without and With IV Contrast MRI is not routinely used for evaluation of the axilla after completion of NAC because it is only 38% to 61% sensitive for detecting residual axillary disease [112-114,120-122]. No imaging test can reliably detect residual nodal disease after NAC, and therefore surgical sampling is the standard of care. Use of MRI for restaging the axilla in clinically node-positive patients is questionable [4]. In a retrospective study of 135 clinically node-positive patients who underwent NAC, MRI evaluation of the axilla after treatment had a low NPV (26%) and therefore could not predict residual axillary disease when a positive MRI of the axilla was defined as node >1 cm, cortex >3 mm, loss of hilum, or irregular contour [121]. In a retrospective study of 269 node-positive patients, postchemotherapy MRI was only 38% sensitive, 76% specific, and 58% accurate in predicting the pathology result of the SLN.

3099208

acrac_3099208_24

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

In a prospective study of 45 patients, 35 of whom were node-positive, there was no association between posttreatment axillary MRI findings and surgical pathology; MRI had a high false negative rate (46%), low sensitivity (55%), and specificity (63%) [114]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in the imaging of known axillary lymph node-positive breast cancer after completion of NAC. US Axilla If the axilla is imaged after NAC, US is the most useful imaging modality, although it only demonstrates moderate sensitivity (53%-86%) and specificity (78%) for detecting residual disease [112,124]. Therefore, surgical sampling of axillary lymph nodes after therapy remains the standard of care. US permits image-guided localization of the clipped metastatic axillary lymph node if the patient is undergoing sentinel node biopsy with surgical excision of the clipped node. The axilla is most commonly imaged after NAC in patients with a clinically positive axilla before therapy [4]. In a retrospective study of 408 clinically node-positive breast cancer patients treated with NAC, the strongest predictor of residual axillary disease was posttreatment US showing axillary lymphadenopathy, defined as axial cortical thickness >3.5 mm or loss of the hilum [125]. The prospective clinical Z1071 trial included 611 patients with US after NAC, 238 of whom had axillary CR. US features associated with residual disease included increased cortical thickness (mean 3.5 mm), absent hilum, and longer lymph node diameter [126]. Monitoring Response to Neoadjuvant Chemotherapy US Breast There is no relevant literature to support the use of breast US alone in the evaluation of known axillary lymph node- positive disease after completion of NAC. However, some studies have shown a correlation between pCR in the breast and the axilla [136].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. In a prospective study of 45 patients, 35 of whom were node-positive, there was no association between posttreatment axillary MRI findings and surgical pathology; MRI had a high false negative rate (46%), low sensitivity (55%), and specificity (63%) [114]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in the imaging of known axillary lymph node-positive breast cancer after completion of NAC. US Axilla If the axilla is imaged after NAC, US is the most useful imaging modality, although it only demonstrates moderate sensitivity (53%-86%) and specificity (78%) for detecting residual disease [112,124]. Therefore, surgical sampling of axillary lymph nodes after therapy remains the standard of care. US permits image-guided localization of the clipped metastatic axillary lymph node if the patient is undergoing sentinel node biopsy with surgical excision of the clipped node. The axilla is most commonly imaged after NAC in patients with a clinically positive axilla before therapy [4]. In a retrospective study of 408 clinically node-positive breast cancer patients treated with NAC, the strongest predictor of residual axillary disease was posttreatment US showing axillary lymphadenopathy, defined as axial cortical thickness >3.5 mm or loss of the hilum [125]. The prospective clinical Z1071 trial included 611 patients with US after NAC, 238 of whom had axillary CR. US features associated with residual disease included increased cortical thickness (mean 3.5 mm), absent hilum, and longer lymph node diameter [126]. Monitoring Response to Neoadjuvant Chemotherapy US Breast There is no relevant literature to support the use of breast US alone in the evaluation of known axillary lymph node- positive disease after completion of NAC. However, some studies have shown a correlation between pCR in the breast and the axilla [136].

3099208

acrac_3099208_25

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

US-Guided Core Biopsy Axillary Node There is no relevant literature to support the use of US-guided core biopsy of the axillary node in imaging of known axillary lymph node-positive breast cancer after completion of NAC. No imaging test can reliably detect residual nodal disease after NAC; therefore, surgical intervention (either sentinel node biopsy or axillary dissection) is necessary after completion of treatment, provided the patient demonstrated a PR or CR warranting surgery and did not undergo axillary surgery before treatment [112,137]. Some centers place a clip in the biopsied positive axillary node before treatment so that it can be surgically excised along with the sentinel node(s) after completion of the NAC; this procedure is sometimes referred to as targeted axillary dissection [138]. US-guided localization of the clipped lymph node can be performed preoperatively [139]. Excising the clipped lymph node and SLN(s) decreases the false-negative rate of SLN biopsy (SLNB) [140]. In a study of 31 patients, 11 patients had residual axillary disease, and, in all cases, the clipped lymph node was positive [141]. In a prospective study of 23 patients with clipped axillary metastases before NAC, the surgeon retrieved the clipped node in 22 cases, and the SLN was retrieved in only 19. The clipped node was the SLN in only 14 cases (61%). The NPV was 100% for removal of clipped and sentinel node but only 85% for SLN removal alone [119]. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no relevant literature to support the use of US-guided FNA of the axillary node in imaging of known axillary lymph node-positive breast cancer after completion of NAC.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. US-Guided Core Biopsy Axillary Node There is no relevant literature to support the use of US-guided core biopsy of the axillary node in imaging of known axillary lymph node-positive breast cancer after completion of NAC. No imaging test can reliably detect residual nodal disease after NAC; therefore, surgical intervention (either sentinel node biopsy or axillary dissection) is necessary after completion of treatment, provided the patient demonstrated a PR or CR warranting surgery and did not undergo axillary surgery before treatment [112,137]. Some centers place a clip in the biopsied positive axillary node before treatment so that it can be surgically excised along with the sentinel node(s) after completion of the NAC; this procedure is sometimes referred to as targeted axillary dissection [138]. US-guided localization of the clipped lymph node can be performed preoperatively [139]. Excising the clipped lymph node and SLN(s) decreases the false-negative rate of SLN biopsy (SLNB) [140]. In a study of 31 patients, 11 patients had residual axillary disease, and, in all cases, the clipped lymph node was positive [141]. In a prospective study of 23 patients with clipped axillary metastases before NAC, the surgeon retrieved the clipped node in 22 cases, and the SLN was retrieved in only 19. The clipped node was the SLN in only 14 cases (61%). The NPV was 100% for removal of clipped and sentinel node but only 85% for SLN removal alone [119]. US-Guided Fine Needle Aspiration Biopsy Axillary Node There is no relevant literature to support the use of US-guided FNA of the axillary node in imaging of known axillary lymph node-positive breast cancer after completion of NAC.

3099208

acrac_3099208_26

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

No imaging test can reliably detect residual nodal disease after NAC; therefore, surgical intervention (either sentinel node biopsy or axillary dissection) is necessary after completion of neoadjuvant treatment, provided the patient demonstrated a PR or CR warranting surgery and did not undergo axillary surgery before treatment [112,137]. Some centers place a clip in the biopsied positive axillary node before treatment so that it can be surgically excised along with the sentinel node(s) after completion of the NAC; this procedure is sometimes referred to as targeted axillary dissection [138]. US-guided localization of the clipped lymph node can be performed preoperatively [139]. Excising the clipped lymph node and SLN(s) decreases the false-negative rate of SLNB [140]. In a study of 31 patients, 11 patients had residual axillary disease, and, in all cases, the clipped lymph node was positive [141]. In a prospective study of 23 patients with clipped axillary metastases before NAC, the surgeon retrieved the clipped node in 22 cases, and the SLN was retrieved in only 19. The clipped node was the SLN in only 14 cases (61%). The NPV was 100% for removal of clipped and sentinel node but only 85% for SLN removal alone [119]. Variant 8: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer. Axillary imaging suspicious for metastatic disease on mammography, US, or MRI during initial evaluation. Next imaging study. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in further evaluation of axillary imaging suspicious for metastatic disease. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. No imaging test can reliably detect residual nodal disease after NAC; therefore, surgical intervention (either sentinel node biopsy or axillary dissection) is necessary after completion of neoadjuvant treatment, provided the patient demonstrated a PR or CR warranting surgery and did not undergo axillary surgery before treatment [112,137]. Some centers place a clip in the biopsied positive axillary node before treatment so that it can be surgically excised along with the sentinel node(s) after completion of the NAC; this procedure is sometimes referred to as targeted axillary dissection [138]. US-guided localization of the clipped lymph node can be performed preoperatively [139]. Excising the clipped lymph node and SLN(s) decreases the false-negative rate of SLNB [140]. In a study of 31 patients, 11 patients had residual axillary disease, and, in all cases, the clipped lymph node was positive [141]. In a prospective study of 23 patients with clipped axillary metastases before NAC, the surgeon retrieved the clipped node in 22 cases, and the SLN was retrieved in only 19. The clipped node was the SLN in only 14 cases (61%). The NPV was 100% for removal of clipped and sentinel node but only 85% for SLN removal alone [119]. Variant 8: Adult female or male or transfeminine (male-to-female) or transmasculine (female-to-male). Known breast cancer. Axillary imaging suspicious for metastatic disease on mammography, US, or MRI during initial evaluation. Next imaging study. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the use of DBT in further evaluation of axillary imaging suspicious for metastatic disease. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections.

3099208

acrac_3099208_27

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in further evaluation of axillary imaging suspicious for metastatic disease. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast There is no relevant literature to support the use of MRI breast with IV contrast in the further evaluation of axillary imaging suspicious for metastatic disease. Monitoring Response to Neoadjuvant Chemotherapy There is robust evidence to support MRI for determining extent of disease in the breast, both before and after NAC [1,4,31,32,35,36,43,63-66]. Although the axillary lymph nodes are included on MRI, it is only moderately sensitive for detection of axillary nodal metastasis before and after therapy [4,112,113]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in the further evaluation of imaging suspicious for metastatic disease. US-Guided Core Biopsy Axillary Node US-guided axillary lymph node sampling is the most useful next study performed when axillary imaging is suspicious for metastatic disease [4]. Sampling of abnormal-appearing nodes by CNB is typically performed using a 14- to 18-gauge device. Some centers place a clip in the biopsied node to facilitate future image-guided localization of the lymph node at surgical excision after completion of NAC. US-guided CNB has proven high specificity, with a moderate to high sensitivity in the detection of metastatic lymph nodes. Houssami et al [33] published a meta-analysis of 2,874 FNA and CNB procedures and found a pooled sensitivity of 80%, a specificity of 98%, and a positive predictive value of 97%.

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in further evaluation of axillary imaging suspicious for metastatic disease. Mammography or DBT is performed for initial diagnosis of the primary breast cancer. This procedure incompletely images the axilla, although pathologically enlarged stage I and II nodes may be included on the lateral and mediolateral oblique projections. MRI Breast Without and With IV Contrast There is no relevant literature to support the use of MRI breast with IV contrast in the further evaluation of axillary imaging suspicious for metastatic disease. Monitoring Response to Neoadjuvant Chemotherapy There is robust evidence to support MRI for determining extent of disease in the breast, both before and after NAC [1,4,31,32,35,36,43,63-66]. Although the axillary lymph nodes are included on MRI, it is only moderately sensitive for detection of axillary nodal metastasis before and after therapy [4,112,113]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast in the further evaluation of imaging suspicious for metastatic disease. US-Guided Core Biopsy Axillary Node US-guided axillary lymph node sampling is the most useful next study performed when axillary imaging is suspicious for metastatic disease [4]. Sampling of abnormal-appearing nodes by CNB is typically performed using a 14- to 18-gauge device. Some centers place a clip in the biopsied node to facilitate future image-guided localization of the lymph node at surgical excision after completion of NAC. US-guided CNB has proven high specificity, with a moderate to high sensitivity in the detection of metastatic lymph nodes. Houssami et al [33] published a meta-analysis of 2,874 FNA and CNB procedures and found a pooled sensitivity of 80%, a specificity of 98%, and a positive predictive value of 97%.

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

Another meta-analysis of 1,353 patients undergoing axillary lymph node biopsy to detect metastases showed that both CNB and FNA procedures performed well, with sensitivities of 74% and 88%, respectively, and a specificity of 100% for both procedures. Complication rates with US-guided biopsies were low, although slightly higher for CNB when compared with FNA (7% versus 1%, respectively), and most commonly included pain, hematoma, and bruising [142]. Some centers place a clip in the biopsied positive axillary node before treatment so that it can be surgically excised along with the sentinel node(s) after completion of the NAC; this procedure is sometimes referred to as targeted axillary dissection [138]. US-guided localization of the clipped lymph node can be performed preoperatively [139]. Excising the clipped lymph node and SLNs decreases the false-negative rate of SLNB [26]. In a study of 31 patients, 11 patients had residual axillary disease, and, in all cases, the clipped lymph node was positive [141]. In a prospective study of 23 patients with clipped axillary metastases before NAC, the surgeon retrieved the clipped node in 22 cases, and the SLN was retrieved in only 19. The clipped node was the SLN in only 14 cases (61%). The NPV was 100% for removal of clipped and sentinel nodes but only 85% for SLN removal alone [119]. Overall, US-guided biopsy offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US-guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy because the completion of axillary surgery is typically performed after therapy [2,117].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Another meta-analysis of 1,353 patients undergoing axillary lymph node biopsy to detect metastases showed that both CNB and FNA procedures performed well, with sensitivities of 74% and 88%, respectively, and a specificity of 100% for both procedures. Complication rates with US-guided biopsies were low, although slightly higher for CNB when compared with FNA (7% versus 1%, respectively), and most commonly included pain, hematoma, and bruising [142]. Some centers place a clip in the biopsied positive axillary node before treatment so that it can be surgically excised along with the sentinel node(s) after completion of the NAC; this procedure is sometimes referred to as targeted axillary dissection [138]. US-guided localization of the clipped lymph node can be performed preoperatively [139]. Excising the clipped lymph node and SLNs decreases the false-negative rate of SLNB [26]. In a study of 31 patients, 11 patients had residual axillary disease, and, in all cases, the clipped lymph node was positive [141]. In a prospective study of 23 patients with clipped axillary metastases before NAC, the surgeon retrieved the clipped node in 22 cases, and the SLN was retrieved in only 19. The clipped node was the SLN in only 14 cases (61%). The NPV was 100% for removal of clipped and sentinel nodes but only 85% for SLN removal alone [119]. Overall, US-guided biopsy offers a minimally invasive option to obtain histopathologic proof of axillary nodal involvement for suspicious findings, although a negative biopsy does not reliably exclude metastatic disease, and therefore surgical pathology remains the reference standard. When US-guided biopsy confirms metastatic disease in pathologic-appearing nodes, it can obviate the need for pretreatment sentinel node biopsy because the completion of axillary surgery is typically performed after therapy [2,117].

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Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer

US-Guided Fine Needle Aspiration Biopsy Axillary Node US-guided axillary lymph node sampling is the most useful next study performed when axillary imaging is suspicious for metastatic disease [4]. Sampling of abnormal-appearing lymph nodes by US-guided FNA is frequently performed with a 22- or 25-gauge needle and also requires the availability of skilled cytopathologists. False-negative rates are low (< 2%) in experienced hands but may occur, especially with smaller metastatic deposits [143]. Some centers place a clip in the biopsied node to facilitate future image-guided localization of the lymph node at surgical excision after completion of NAC. US-guided axillary FNA has proven high specificity, with a moderate to high sensitivity in the detection of metastatic lymph nodes. A retrospective study of 65 patients compared US-guided FNA results to final surgical pathology in patients with radiographically suspicious lymph nodes and demonstrated high sensitivity, specificity, and positive predicative value (89%, 100% and 100%, respectively) for FNA [144]. A larger meta-analysis of 1,353 patients undergoing axillary lymph node biopsy to detect metastases showed that both FNA and CNB performed well, with sensitivities of 74% and 88%, respectively, and a specificity of 100% for both procedures. Complication rates for FNA were lower than CNB (1% versus 7%, respectively) and were most commonly pain, hematoma, and bruising [142]. Additionally, one prospective study of combined axillary US and FNA in 315 patients with sonographically positive lymph nodes again demonstrated high sensitivity (81%), specificity (100%), and positive predictive value (100%). However, the NPV was low (50%), supporting the need for definitive surgical sampling [145].

Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. US-Guided Fine Needle Aspiration Biopsy Axillary Node US-guided axillary lymph node sampling is the most useful next study performed when axillary imaging is suspicious for metastatic disease [4]. Sampling of abnormal-appearing lymph nodes by US-guided FNA is frequently performed with a 22- or 25-gauge needle and also requires the availability of skilled cytopathologists. False-negative rates are low (< 2%) in experienced hands but may occur, especially with smaller metastatic deposits [143]. Some centers place a clip in the biopsied node to facilitate future image-guided localization of the lymph node at surgical excision after completion of NAC. US-guided axillary FNA has proven high specificity, with a moderate to high sensitivity in the detection of metastatic lymph nodes. A retrospective study of 65 patients compared US-guided FNA results to final surgical pathology in patients with radiographically suspicious lymph nodes and demonstrated high sensitivity, specificity, and positive predicative value (89%, 100% and 100%, respectively) for FNA [144]. A larger meta-analysis of 1,353 patients undergoing axillary lymph node biopsy to detect metastases showed that both FNA and CNB performed well, with sensitivities of 74% and 88%, respectively, and a specificity of 100% for both procedures. Complication rates for FNA were lower than CNB (1% versus 7%, respectively) and were most commonly pain, hematoma, and bruising [142]. Additionally, one prospective study of combined axillary US and FNA in 315 patients with sonographically positive lymph nodes again demonstrated high sensitivity (81%), specificity (100%), and positive predictive value (100%). However, the NPV was low (50%), supporting the need for definitive surgical sampling [145].

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Cerebrovascular Disease Child PCAs

Perinatal stroke (<6 months of age), although the most common acute stroke in children (20 to 62.5/100,000 live births), will not be discussed in this topic. As in many cases, the diagnosis is retrospective when the child presents later in life with new onset seizure, asymmetric motor function, or failure of developmental milestones [8]. The majority of perinatal stroke is likely to be caused by thromboembolism from the placenta through a patent foramen ovale or fetal heart defect [8]. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] and 25% presented outside of the therapeutic window [2]. The study was closed by the NIH for lack of patient accrual [2]. To date, there is insufficient information about acute pediatric stroke to confirm the appropriate window for initiation of thrombolytic therapy in children [12]. A window of 24 hours from stroke onset to initiation of treatment is used in this clinical scenario. This treatment is considered in children >2 years of age [13]. The risk of symptomatic hemorrhage into an ischemic infarction in adults treated with IV tissue-type plasminogen activator is 6.4% and is unknown in children [2]. Recently, interest in the use of intra-arterial treatment for stroke in children has developed because of the documented success of this type of therapy in adults. However, currently, no systematic study of such therapy in children has been performed, and only case reports exist [14]. Adult studies have shown good results with mechanical thrombectomy up to 6 hours or longer on a case-by-case basis from acute stroke symptom onset [15].

Cerebrovascular Disease Child PCAs. Perinatal stroke (<6 months of age), although the most common acute stroke in children (20 to 62.5/100,000 live births), will not be discussed in this topic. As in many cases, the diagnosis is retrospective when the child presents later in life with new onset seizure, asymmetric motor function, or failure of developmental milestones [8]. The majority of perinatal stroke is likely to be caused by thromboembolism from the placenta through a patent foramen ovale or fetal heart defect [8]. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] and 25% presented outside of the therapeutic window [2]. The study was closed by the NIH for lack of patient accrual [2]. To date, there is insufficient information about acute pediatric stroke to confirm the appropriate window for initiation of thrombolytic therapy in children [12]. A window of 24 hours from stroke onset to initiation of treatment is used in this clinical scenario. This treatment is considered in children >2 years of age [13]. The risk of symptomatic hemorrhage into an ischemic infarction in adults treated with IV tissue-type plasminogen activator is 6.4% and is unknown in children [2]. Recently, interest in the use of intra-arterial treatment for stroke in children has developed because of the documented success of this type of therapy in adults. However, currently, no systematic study of such therapy in children has been performed, and only case reports exist [14]. Adult studies have shown good results with mechanical thrombectomy up to 6 hours or longer on a case-by-case basis from acute stroke symptom onset [15].

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Cerebrovascular Disease Child PCAs

CT Head CT of the head is frequently the front-line imaging study for the assessment of a child with a suspected acute stroke. Although CT is less sensitive than MRI for the early depiction of acute ischemic infarction, the technique is rapid, usually does not require the child to be sedated, and can be useful in evaluating for hemorrhage or in excluding other treatable pathologies [16]. CTA Head CT angiography (CTA) can provide a useful assessment of intracranial vessels in arteriopathies and thromboembolic disease [17]. MRA Head MR angiography (MRA) can provide information on the intracranial vasculature and is particularly helpful in noninvasive assessment of arteriopathies [17]. MRA is susceptible to flow-related artifacts that may simulate regions of stenosis, especially in the setting of turbulence that may occur with anemia at vessel branch points [26]. MRI and MRA of the cervical vessels in cases of unexplained stroke should be considered, with attention paid to the time constraints of the window of therapeutic intervention [27]. MRA can be performed with IV contrast to improve vessel delineation, although contrast is not typically required to produce diagnostic imaging in acute stroke. CT Head Perfusion Perfusion CT in children is feasible but requires repetitive imaging of the brain [28]. MR Head Perfusion Perfusion-weighted MR can be performed with either dynamic susceptibility contrast administration or arterial spin-label techniques without IV contrast and can provide information on the adequacy of cerebral blood flow [17,19,29]. Perfusion MR is not necessary to proceed to emergent acute stroke thrombolysis. CT Head CT of the head is frequently the initial imaging study for the assessment of a child with a suspected acute stroke.

Cerebrovascular Disease Child PCAs. CT Head CT of the head is frequently the front-line imaging study for the assessment of a child with a suspected acute stroke. Although CT is less sensitive than MRI for the early depiction of acute ischemic infarction, the technique is rapid, usually does not require the child to be sedated, and can be useful in evaluating for hemorrhage or in excluding other treatable pathologies [16]. CTA Head CT angiography (CTA) can provide a useful assessment of intracranial vessels in arteriopathies and thromboembolic disease [17]. MRA Head MR angiography (MRA) can provide information on the intracranial vasculature and is particularly helpful in noninvasive assessment of arteriopathies [17]. MRA is susceptible to flow-related artifacts that may simulate regions of stenosis, especially in the setting of turbulence that may occur with anemia at vessel branch points [26]. MRI and MRA of the cervical vessels in cases of unexplained stroke should be considered, with attention paid to the time constraints of the window of therapeutic intervention [27]. MRA can be performed with IV contrast to improve vessel delineation, although contrast is not typically required to produce diagnostic imaging in acute stroke. CT Head Perfusion Perfusion CT in children is feasible but requires repetitive imaging of the brain [28]. MR Head Perfusion Perfusion-weighted MR can be performed with either dynamic susceptibility contrast administration or arterial spin-label techniques without IV contrast and can provide information on the adequacy of cerebral blood flow [17,19,29]. Perfusion MR is not necessary to proceed to emergent acute stroke thrombolysis. CT Head CT of the head is frequently the initial imaging study for the assessment of a child with a suspected acute stroke.

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Cerebrovascular Disease Child PCAs

Although CT is less sensitive than MRI for the early depiction of acute ischemic infarction, the technique is rapid, usually does not require the child to be sedated, and can be useful in evaluating for hemorrhage or in excluding other treatable pathologies [16]. CTA Head CTA can provide a useful assessment of intracranial vessels in arteriopathies and thromboembolic disease [17]. MRA Head MRA can provide information on the intracranial vasculature and is particularly helpful in noninvasive assessment of arteriopathies [17]. MRA is susceptible to flow-related artifacts that may simulate regions of stenosis, especially in the setting of turbulence that may occur with anemia at vessel branch points [26]. MRI and MRA should include the cervical vessels in cases of unexplained stroke because cerebral arterial abnormalities are found in 25% of patients [27]. CT Head Perfusion Perfusion CT in children is feasible but requires repetitive imaging of the brain [28]. MR Head Perfusion Perfusion-weighted MR can be performed with either dynamic susceptibility contrast administration or arterial spin-label techniques without IV contrast and can provide information on the adequacy of cerebral blood flow [17,19,29]. US Duplex Doppler Transcranial Using an open fontanel as an acoustic window, ultrasound (US) can be used to diagnose infarction in the neonate but MRI, as in the older child, is more definitive. US shows 68% of infarctions in the first 3 days of life and 87% within the first 2 weeks [34]. Detailed evaluation of the brain parenchyma is generally not possible with US following the closure of the fontanels, but Doppler US can be used to interrogate flow in the intracranial vessels [35]. Variant 3: Child. Clinical presentation suggestive of acute stroke, known or suspected arteriopathy, or moyamoya. Not a candidate for emergent treatment. Initial imaging.

Cerebrovascular Disease Child PCAs. Although CT is less sensitive than MRI for the early depiction of acute ischemic infarction, the technique is rapid, usually does not require the child to be sedated, and can be useful in evaluating for hemorrhage or in excluding other treatable pathologies [16]. CTA Head CTA can provide a useful assessment of intracranial vessels in arteriopathies and thromboembolic disease [17]. MRA Head MRA can provide information on the intracranial vasculature and is particularly helpful in noninvasive assessment of arteriopathies [17]. MRA is susceptible to flow-related artifacts that may simulate regions of stenosis, especially in the setting of turbulence that may occur with anemia at vessel branch points [26]. MRI and MRA should include the cervical vessels in cases of unexplained stroke because cerebral arterial abnormalities are found in 25% of patients [27]. CT Head Perfusion Perfusion CT in children is feasible but requires repetitive imaging of the brain [28]. MR Head Perfusion Perfusion-weighted MR can be performed with either dynamic susceptibility contrast administration or arterial spin-label techniques without IV contrast and can provide information on the adequacy of cerebral blood flow [17,19,29]. US Duplex Doppler Transcranial Using an open fontanel as an acoustic window, ultrasound (US) can be used to diagnose infarction in the neonate but MRI, as in the older child, is more definitive. US shows 68% of infarctions in the first 3 days of life and 87% within the first 2 weeks [34]. Detailed evaluation of the brain parenchyma is generally not possible with US following the closure of the fontanels, but Doppler US can be used to interrogate flow in the intracranial vessels [35]. Variant 3: Child. Clinical presentation suggestive of acute stroke, known or suspected arteriopathy, or moyamoya. Not a candidate for emergent treatment. Initial imaging.

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Cerebrovascular Disease Child PCAs

Arteriopathies, defined as intrinsic vessel stenosis, irregularity, pseudoaneurysm, banding, or dissection flap, account for 18% to 64% of pediatric ischemic stroke cases [36]. Common causes of arteriopathy include moyamoya (22%), arterial dissection (15% to 20%), vasculitis (12%), and sickle cell disease (SCD) arteriopathy (8%) [27,36]. Genetic mutation constitutes an increasingly represented etiology of cerebral arteriopathy as demonstrated by mutations in the ACTA2 or CERC 1 genes. Arteriopathies are a strong indicator of recurrent stroke risk (66%) [36-38]. Moyamoya refers to the angiographic appearance of a progressive stenosis or occlusion of the internal carotid artery apex and proximal branches of the circle of Willis with the development of stereotypical collaterals. Moyamoya occurs in approximately one in every 1 million children in the United States and accounts for 6% of all pediatric strokes [39]. The underlying cause is unclear, but it is likely that many different factors, both genetic and environmental, contribute to developing the arteriopathy. The moyamoya syndrome may be idiopathic (moyamoya disease) or occur in association with other conditions (moyamoya syndrome). Up to 40% of children with SCD may show moyamoya-like changes on imaging [39]. Moyamoya disease is, by definition, bilateral but may be asymmetric in severity [39]. Unilateral involvement is considered moyamoya syndrome. As many as 12% of patients with sickle cell anemia will have a clinically detected stroke by the age of 20 [40,41]. Importantly, at a minimum, 85% of patients with sickle cell anemia who present with frank stroke will have evidence of cerebral arteriopathy on neuroimaging [41,42]. Most strokes in moyamoya in children are ischemic and most frequently occur in the vascular border zone territories, but cortical infarctions can occur as well.

Cerebrovascular Disease Child PCAs. Arteriopathies, defined as intrinsic vessel stenosis, irregularity, pseudoaneurysm, banding, or dissection flap, account for 18% to 64% of pediatric ischemic stroke cases [36]. Common causes of arteriopathy include moyamoya (22%), arterial dissection (15% to 20%), vasculitis (12%), and sickle cell disease (SCD) arteriopathy (8%) [27,36]. Genetic mutation constitutes an increasingly represented etiology of cerebral arteriopathy as demonstrated by mutations in the ACTA2 or CERC 1 genes. Arteriopathies are a strong indicator of recurrent stroke risk (66%) [36-38]. Moyamoya refers to the angiographic appearance of a progressive stenosis or occlusion of the internal carotid artery apex and proximal branches of the circle of Willis with the development of stereotypical collaterals. Moyamoya occurs in approximately one in every 1 million children in the United States and accounts for 6% of all pediatric strokes [39]. The underlying cause is unclear, but it is likely that many different factors, both genetic and environmental, contribute to developing the arteriopathy. The moyamoya syndrome may be idiopathic (moyamoya disease) or occur in association with other conditions (moyamoya syndrome). Up to 40% of children with SCD may show moyamoya-like changes on imaging [39]. Moyamoya disease is, by definition, bilateral but may be asymmetric in severity [39]. Unilateral involvement is considered moyamoya syndrome. As many as 12% of patients with sickle cell anemia will have a clinically detected stroke by the age of 20 [40,41]. Importantly, at a minimum, 85% of patients with sickle cell anemia who present with frank stroke will have evidence of cerebral arteriopathy on neuroimaging [41,42]. Most strokes in moyamoya in children are ischemic and most frequently occur in the vascular border zone territories, but cortical infarctions can occur as well.

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