Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. There is no relevant literature specifically comparing the performance of DBT to mammography after initiation or completion of NAC.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 7 Monitoring Response to Neoadjuvant Chemotherapy


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. There is no relevant literature specifically comparing the performance of DBT to mammography after initiation of completion of NAC.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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]. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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 Systemic Therapy for Breast Cancer. Monitoring Response to Neoadjuvant Chemotherapy


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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]. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging evaluation of the axilla before NAC.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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]. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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, 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


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 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in initial imaging of the axilla after NAC [4].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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 Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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]. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 13 Monitoring Response to Neoadjuvant Chemotherapy


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. The axilla is incompletely visualized on the mediolateral and lateral projections, thereby limiting the use of these modalities to reliably detect residual disease.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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 Systemic Therapy for Breast Cancer. 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. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. Mammography Diagnostic There is no relevant literature to support the use of diagnostic mammography in further evaluation of axillary imaging suspicious for metastatic disease.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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 Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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%. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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. 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


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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 node but only 85% for SLN removal alone [119].


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 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.


Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. Monitoring Response to Neoadjuvant Chemotherapy For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Cerebrovascular Disease Child PCAs

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].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Reprint requests to: publications@acr.org


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. and 25% presented outside of the therapeutic window [2]. The study was closed by the NIH for lack of patient accrual [2].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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

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].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CT angiography (CTA) can provide a useful assessment of intracranial vessels in arteriopathies and thromboembolic disease [17].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head Perfusion Perfusion CT in children is feasible but requires repetitive imaging of the brain [28].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head CT of the head is frequently the initial 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].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA can provide a useful assessment of intracranial vessels in arteriopathies and thromboembolic disease [17].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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].


Cerebrovascular Disease Child PCAs


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. following the closure of the fontanels, but Doppler US can be used to interrogate flow in the intracranial vessels [35].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 3: Child. Clinical presentation suggestive of acute stroke, known or suspected arteriopathy, or moyamoya. Not a candidate for emergent treatment. Initial imaging. 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

Cerebrovascular Disease Child PCAs. CT Head CT is less sensitive than MRI for demonstrating acute infarctions but can be useful in evaluating rare instances of intracranial hemorrhage in moyamoya [43].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA, including multiphase CTA, is an alternative to MRA and catheter angiography in the initial diagnosis and follow-up of children with moyamoya.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head Proposed screening guidelines for moyamoya include diagnostic imaging using MRI/MRA in at-risk populations, particularly if there are symptoms of cerebral ischemia. Screening of first-degree relatives of patients with moyamoya is probably not warranted in the absence of symptoms or unless multiple family members are already known to be affected. T2-weighted fluid-attenuated inversion-recovery imaging may show high signal in the sulci (ivy sign), indicative of slow flow in affected vascular territories. A similar appearance may be evident on T1- weighted contrast-enhanced studies. SWI may be used to demonstrate microhemorrhage that has been reported in up to 52% of patients [44]. Arteriopathy can also be further evaluated with the technique of vessel-wall imaging [15,45].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head MRA is an alternative to CTA in the initial and follow-up imaging evaluation of children with moyamoya and is the preferred noninvasive vascular imaging modality. MRA is typically performed together with brain MRI to evaluate both the cerebral vasculature and the brain parenchyma.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head Perfusion The use of perfusion CT, including xenon-enhanced CT, in children with moyamoya is feasible but requires repetitive imaging of the brain [28].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MR Head Perfusion MR cerebral blood flow evaluation includes perfusion-weighted MR, either using arterial spin-labeling techniques without IV contrast or dynamic susceptibility contrast techniques with IV contrast. Perfusion imaging is also used to assess functional improvement after treatment [39,46-49].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. HMPAO SPECT or SPECT/CT Brain Single-photon-emission computed tomography (SPECT) studies can be used to assess perfusion in patients with moyamoya and can be augmented with acetazolamide challenge to assess perfusion instability and vascular reserve. Perfusion imaging is also used to assess functional improvement after treatment [39].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography is required for definitive diagnosis of moyamoya and is typically obtained as part of a preoperative assessment prior to surgical revascularization or following revascularization to assess the development of surgically created collaterals.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial Head US does not typically play a role in the management of children with moyamoya.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 4: Child. Known or suspected cervicocranial arterial dissection based on clinical or imaging findings. Next imaging study. Cervicocranial artery dissection occurs in 2.5/100,000 children per year and is up to 4 times more common in children than in adults [50-52]. Purely intracranial dissections are also more common in children than adults [50]. Patients with cervical artery dissection can present with headache, neck pain, or ischemic infarction due to emboli, whereas patients with intracranial artery dissection can present with ischemic infarction, subarachnoid hemorrhage (SAH), or symptoms due to local mass effect [50,52]. A history of antecedent trauma may or may not be present.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head CT can show areas of infarction or SAH although the sensitivity of CT is less than that of MRI with DWI for demonstrating acute infarction [43]. A crescent-shaped hyperattenuating area in a cranial or cervical artery is consistent with an intramural hematoma and is highly suggestive of dissection [52].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head and Neck CTA can demonstrate vessel narrowing, pseudoaneurysm, or an intimal flap in dissection [50,52].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head and Neck MRI is the preferred study for the demonstration of infarction due to cervicocranial arterial dissection [50,52,53]. DWI and perfusion-weighted MRI provide information on regions of infarction. SWI can demonstrate emboli, and increased oxygen extraction leads to prominence of the veins in infarcted regions. T1-weighted imaging with fat suppression or T2-weighted imaging may demonstrate an intramural hematoma in 76% to 91% of patients with dissection [50,52].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head and Neck MRA without or with IV contrast may be used to assess for cervicocranial artery dissection to demonstrate an intimal flap, vessel narrowing, or pseudoaneurysm formation [52,53].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography remains the gold standard for the radiologic evaluation of dissection but is typically reserved for patients in whom dissection is suspected but not confirmed on noninvasive imaging [52,53]. Angiography may reveal vessel narrowing, pseudoaneurysm formation, or an intimal flap in regions of dissection and distal vessel occlusions due to emboli.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial and Carotid Artery Doppler US may be used to evaluate the cervical internal carotid arteries for dissection. The technique is of limited utility for carotid dissections at or above the skull base and in the evaluation of the vertebral arteries because of a lack of a good acoustic window [52].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 5: Child. Clinical presentation suggestive of acute stroke, known or suspected central nervous system vasculitis. Initial imaging. Childhood vasculitis is as an inflammatory process only affecting the intracranial vessels and can result in stroke. It can present as childhood primary angiitis of the central nervous system or as a secondary phenomenon in systemic rheumatologic infections and neoplastic conditions [54]. Childhood primary angiitis of the central nervous system is subcategorized into large-medium vessel vasculitis (angiography positive) or small vessel (vessel abnormality too small to be demonstrated on MRA, CTA, or conventional angiography) best diagnosed by brain biopsy [55]. The diagnosis of childhood primary angiitis of the central nervous system requires an acquired


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. neurologic deficit, angiographic or histologic features of central nervous system vasculitis, and no evidence of a systemic condition associated with the central nervous system findings.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head Evaluation of central nervous system vasculitis by CT is typically negative [56].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA can provide a noninvasive assessment of intracranial vessels in arteriopathies as an alternative to catheter angiography in some patients but is typically negative in small-vessel vasculitis (eg, childhood primary angiitis of the central nervous system) [17].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head MRI typically shows progressive multifocal parenchymal lesions on T2-weighted imaging. Gadolinium enhancement of lesions is inconsistent.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head MRA can provide a noninvasive assessment of intracranial vessels in arteriopathies as an alternative to catheter angiography in some patients but is typically negative in small vessel-vasculitis (eg, childhood primary angiitis of the central nervous system) [17].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography is the most sensitive imaging method in the assessment of cerebral vasculitis but is typically negative in small-vessel vasculitis (eg, childhood primary angiitis of the central nervous system) [17].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial Head US in not usually indicated in the evaluation of cerebral vasculitis.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 6: Child. Nontraumatic intraparenchymal hemorrhage (hematoma) found on CT or MRI. Unknown etiology. Next imaging study. Approximately half of all strokes beyond the perinatal period are hemorrhagic, whereas only 6.5% to 13% of strokes in adults are hemorrhagic [57,58]. Hemorrhagic strokes are associated with a variety of etiologies, including arteriovenous fistula or arteriovenous malformation (48%), brain tumors (15%), genetic or acquired coagulopathy (9%), thrombocytopenia (6%), cavernous malformation (5%), and coagulopathy and aneurysm (2%) [58]. Presenting symptoms of hemorrhagic stroke differ with respect to the age of the child but may include mental status changes, seizures, or focal neurologic deficit.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head Unenhanced head CT is useful to assess the location and size of hemorrhage, evidence of mass effect, and hydrocephalus [59]. IV contrast may be helpful in demonstrating an underlying cause for the hemorrhage, such as vascular malformation, aneurysm, or tumor.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA may be used to delineate the vascular anatomy and may be used to demonstrate a vascular malformation or aneurysm but lacks the temporal information available from catheter angiography.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head Unenhanced MRI can delineate the location and size of hemorrhage, evidence of mass effect, and hydrocephalus and may show evidence of an underlying structural lesion, such as vascular malformation, aneurysm, or tumor. SWI and arterial spin-labeling imaging may improve the delineation of the draining veins and arteriovenous shunting, respectively, compared with conventional MR sequences [24]. Contrast may be required to demonstrate small malformations, such as those that may occur in hereditary hemorrhagic telangiectasia, or other causes of parenchymal hematoma, such as tumor.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head MRA may be used to delineate the vascular anatomy and may be used to demonstrate a vascular malformation or aneurysm but lacks the temporal information available from catheter angiography.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography is the gold standard for imaging of high-flow vascular malformations and aneurysms [60]. Although developmental venous anomalies (DVAs) can be demonstrated on catheter angiography, cavernoma and capillary telangiectasia are angiographically occult [61].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 7: Child. Nontraumatic subarachnoid hemorrhage (SAH) detected by noncontrast CT. Next imaging study. Fifty-seven percent of SAH in children is due to aneurysm; however, only 2% to 15% of hemorrhagic strokes in children are due to aneurysm [58,62]. Aneurysms in children account for <1% of SAH due to aneurysms in all age groups [62]. The mortality in pediatric aneurysm has been reported to be 1.3%, with morbidity including infarction (8%) and seizures (4%) [63]. Only 0.6% of ruptured aneurysms occur in patients <19 years of age [51,60]. Aneurysms in children are idiopathic (45%), post-traumatic (20%), or due to a variety of conditions causing abnormal vessel-wall hemodynamic stress [62]. In contrast to adults, aneurysms in children are more likely to be giant (>25 mm) or fusiform [62]. Children with a positive family history of aneurysm account for <5% of pediatric aneurysms, and fewer than 2% of patients with a positive family history of aneurysm develop an aneurysm in the first two decades of life [62]. Fusiform aneurysms are more likely to increase in size over time than are saccular aneurysms [64].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head The initial imaging study in suspected SAH is a noncontrast head CT. If the CT is negative for SAH, lumbar puncture may be performed. Unenhanced head CT is useful in ruptured aneurysms to assess the location and size of hemorrhage, evidence of mass effect, and hydrocephalus [59]. Small aneurysms are difficult to evaluate with unenhanced CT whereas a giant aneurysm, if present, appears as a hyperdense mass.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA is a noninvasive alternative to catheter angiography to show an underlying vascular cause of SAH with reported sensitivity (96.5%) and specificity (88%) for aneurysms of all sizes with sensitivity (98.4%) and specificity (100%) for aneurysms >3 mm [65]. CTA is used to confirm the presence of aneurysm and may be used as an adjunct to catheter angiography in the pretreatment assessment of aneurysm. CTA provides an alternative to catheter angiography for assessing residual or recurrent aneurysm but may be limited by streak artifact from the treatment device. Using digital subtraction angiography as the gold standard, CTA has a reported sensitivity of 74% and specificity of 96% for the demonstration of residual aneurysm post-treatment [66].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head MRI is not typically an initial imaging study in patients with suspected SAH. However, SWI is sensitive to the presence of subarachnoid blood. MRI may be useful in classifying the aneurysms into saccular, dissecting, giant, and infectious [60]. MRI may be used to evaluate potential complications of treatment, including cerebral infarction or hemorrhage [63]. Only patients with MRI-safe aneurysm clips should be imaged with MR.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head MRA is a noninvasive alternative to catheter angiography to show an underlying vascular cause of SAH. MRA of the brain is the examination of choice for children with unruptured aneurysms being followed prior to treatment [51]. A meta-analysis of the literature shows the sensitivity and specificity of MRA for the detection of intracranial aneurysm to be 95% and 89%, respectively [67]. Given the limited number of children who will develop an aneurysm under the age of 20, routine screening with MRA of children with a positive family history of aneurysm is not supported in the literature [68].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography remains the gold standard for the demonstration of high-flow vascular anomalies and aneurysms as a cause of SAH. Catheter angiography can be performed for pretreatment planning and for post- treatment assessment. Catheter angiography is associated with a low incidence of procedural complications in children [51,60]. Catheter angiography is the gold standard for the diagnosis and pretreatment evaluation of intracranial aneurysm and may also be required for post-treatment follow-up in some patients [60].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial Head US is not sensitive for the presence of subarachnoid blood or vascular causes of intracranial hemorrhage. Head US provides limited information on intracranial aneurysm, but Doppler US may be used to confirm the vascular nature of a mass seen on head US performed in neonates and young infants with open fontanels.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head Unenhanced head CT is useful in hemorrhagic high-flow vascular anomalies to assess the location and size of hemorrhage, evidence of mass effect, and hydrocephalus [59]. High-flow vascular malformations that have not bled are slightly hyperdense relative to brain on unenhanced head CT. The detection of a high-flow vascular anomaly that has not bled may be improved with the use of IV contrast.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA is often used to delineate the anatomy of a high-flow vascular anomaly but lacks the temporal information available from catheter angiography. CTA may be used to monitor the lesion prior to treatment or to assess for growth or recurrence after treatment.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head MRI is used to determine the location and size of high-flow vascular anomalies and is often preferred to CT for use in children. SWI and arterial spin-labeling imaging may improve the delineation of the draining veins and arteriovenous shunting, respectively, compared with conventional MRI sequences [24]. Contrast may be required to demonstrate small malformations.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head MRA, like CTA, can be used to delineate the anatomy of a high-flow vascular anomaly but lacks the temporal information available from catheter angiography. MRA is often preferable to CTA in children for following vascular anomalies serially. The use of IV contrast may be required to assess the venous outflow of the anomaly. MRA may be used to monitor the anomaly prior to treatment or to assess for growth or recurrence after treatment.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral With the increased accuracy of the noninvasive imaging studies CTA and MRA, catheter angiography is not typically used as the initial diagnostic imaging for suspected high-flow vascular anomaly. Catheter angiography can be used for pretreatment evaluation and post-treatment assessment of any residual anomaly [59,71].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial Head US with Doppler may be used to show the presence of large high-flow vascular malformations, such as vein of Galen malformation and dural arteriovenous fistula or malformation in neonates and young infants. US is useful in very young children because it can be performed without sedation or anesthesia, which may be required for MRI examinations.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 9: Child. Clinical presentation suggestive of acute stroke, known or suspected low-flow vascular anomaly. Initial imaging. Low-flow vascular anomalies include cavernous malformation, DVA, and capillary telangiectasia. Cavernomas are comprised of endothelial spaces containing venous blood and account for 17% of hemorrhagic stroke in children [18]. In a large series, 62% of children with cavernomas presented with hemorrhage, 35% with seizures with or without hemorrhage, and 26% had cavernomas discovered incidentally [72]. Patients with cavernoma (15%) have multiple lesions and 10% have a family history of cavernoma and may have mutations in CCM1, CCM2, and CCM3 genes [72-74]. Although 9% are associated with prior cranial irradiation [72], 86% are supratentorial and 14% infratentorial in location. Cavernomas have an annual hemorrhage rate of 3.3% to 4.5% [72,75]. DVA is an anomalous vein draining normal brain parenchyma, and 20% of DVA are associated with


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. cavernoma [72]. Most hemorrhage in patients with DVA is believed to be due to bleeding from an associated cavernoma [61,72].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head Noncontrast CT can show acute hemorrhage with cavernoma. Nonhemorrhagic cavernomas and DVA may be faintly hyperdense on noncontrast imaging [61]. IV contrast increases the conspicuity of DVA.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA plays a limited role in the assessment of cavernoma but may be used to demonstrate a DVA.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head MRI is the imaging study of choice for cavernoma. Various stages of hemorrhage may be evident. T2-weighted gradient-echo imaging or SWI may show additional cavernomas not seen on spin-echo imaging. The presence of acute and subacute blood products increases the likelihood of future hemorrhage [75]. DVAs are visible on both spin-echo and gradient-echo imaging and are occasionally associated with gliosis or cortical malformation. Contrast may increase the conspicuity of DVA.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head MRA is not usually helpful in the assessment of cavernoma, capillary telangiectasia, and DVA.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography is rarely required for the evaluation of incidentally discovered DVA but may be used to exclude the possibility of an associated high-flow vascular malformation. An isolated DVA appears as an abnormal cluster of veins draining into a single collector and appears only on the venous phase of the arteriogram [61]. Cavernomas and capillary telangiectasia are usually angiographically occult.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial Head US is not usually helpful in the assessment of cavernoma or capillary telangiectasia. Head US may occasionally be used to demonstrate large DVA in neonates and young infants with open fontanels.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 10: Child. Clinical presentation suggestive of acute stroke, known or suspected cortical vein or dural venous sinus thrombosis. Initial imaging. Cerebral sinovenous thrombosis has an incidence of 1/200,000 children per year. It is less common in children than is arterial ischemic or hemorrhagic stroke and is most often associated with infection, trauma, dehydration, cancer, oral contraceptives, and prothrombotic disorders [76,77]. The risk is highest in the first year of life, with neonates accounting for 61% of cerebral sinovenous thrombosis [76-78]. Prothrombotic disorders are present in more than half of children, and multiple risk factors are commonly present. An acute illness with sepsis and dehydration is present in up to one-third of patients. Trauma is more common in older children. Cerebral sinovenous thrombosis can cause elevation in venous pressure, increased intracranial pressure, and venous infarction. Hemorrhagic infarction (40%) and hydrocephalus (10%) may complicate cerebral sinovenous thrombosis [77]. Infarctions are more frequently hemorrhagic in neonates (72%) than in older children (48%) [79]. The lateral dural venous sinuses (73%) and superior sagittal sinus (35%) are most commonly affected [76- 78].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head CT Head Unenhanced CT shows increased density, often accompanied by distension, of the thrombosed sinus or vein [77,80]. CT is less sensitive than MRI for the demonstration of early ischemic infarction but readily shows areas of brain hemorrhage [77,79].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRV Head MRV is used to diagnose and follow cortical vein and dural venous sinus thrombosis and is typically performed in conjunction with anatomic MRI without and with IV contrast for a comprehensive assessment of the intracranial venous drainage. MRV without IV contrast is commonly used to confirm absence of flow in a thrombosed dural venous sinus. MRV with IV contrast is less susceptible to the flow artifacts that may occur because of turbulent flow in the dural venous sinuses with noncontrast MRV [80].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography is not routinely used for the diagnosis of cortical venous or dural venous sinus thrombosis but is used when endovascular treatment is required.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial Head US with Doppler may be used to assess patency of the dural venous sinuses in the neonate. Following closure of the fontanels, CT and MRI are more commonly used.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Variant 11: Child. Clinical presentation suggestive of acute stroke, sickle cell disease. New focal fixed or worsening neurologic defect. Initial imaging. SCD constitutes one of the main etiologies of pediatric stroke. Eleven percent of children with SCD not receiving primary stroke prevention therapy will have a stroke by 20 years of age [36,82,83]. Most infarctions are due to vasculopathy involving the supraclinoid portion of the internal carotid artery or branches of the circle of Willis and occurring in a watershed distribution. Clinically silent infarctions are known to occur in 17% of children with SCD [84]. The National Heart Lung and Blood institute recommends that children with SCD between 2 and 16 years of age undergo transcranial Doppler US screening every 6 months. The treatment of acute stroke symptoms in children with SCD is transfusion.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CT Head CT is relatively insensitive compared with MRI for the demonstration of infarction and is typically only used in the acute setting if MRI is unavailable or to document hemorrhage or evaluate for mass effect [26].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. CTA Head CTA is not used in routine neurovascular screening in children with SCD. CTA can be used in children with contraindication to MRA.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRI Head MRI can show T2 prolongation in watershed vascular territories or cortex in patients with SCD.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. MRA Head MRA is the study of choice to screen for vessel stenosis in children with SCD with elevated transcranial Doppler US velocities in the intracranial vessels [39,44]. Although MRA can accurately show vessel stenosis, it is susceptible to false-positive results when long echo times are used or when severe anemia is present, resulting in turbulent blood flow and localized artefactual signal loss resembling focal stenosis [26,84,85]. Although gadolinium-enhanced MRA can be used, it is generally not required and is often avoided because of concerns that it may potentiate hemolysis in patients with SCD [26]. MRI of the brain without IV contrast is typically performed during the same examination as the MRA to assess the brain parenchyma for ischemic injury.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. Arteriography Cervicocerebral Catheter angiography is generally not indicated except in uncommon circumstances, including preoperative assessment for revascularization for moyamoya syndrome and suspected aneurysm complicating SCD [26].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. US Duplex Doppler Transcranial The National Heart Lung and Blood institute recommends that children with SCD between 2 and 16 years of age to undergo transcranial Doppler US screening every 6 months [35]. Velocity measurements from the distal internal carotid artery or proximal middle cerebral artery are used to assess stroke risk. Time averaged means of maximum velocity of <170 cm/sec are associated with a low risk of stroke, velocities of 170 to 199 cm/sec are associated with an intermediate risk of stroke, and velocities of >200 cm/sec are associated with a high risk of stroke (40%) in the next 3 years [35,86].


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. 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.


Cerebrovascular Disease Child PCAs

Cerebrovascular Disease Child PCAs. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Pancreatic Cyst

Pancreatic Cyst. Introduction/Background Incidental pancreatic cysts are now increasingly detected on imaging studies performed for unrelated indications. [1-3]. Both increased imaging utilization and improved cross-sectional technique are responsible for the more frequent detection of progressively smaller cysts [4-6]. The most commonly encountered pancreatic cysts include intraductal papillary mucinous neoplasms (IPMNs), serous cystadenoma, mucinous cystic neoplasm (MCN), and pseudocysts [6,7].


Pancreatic Cyst

Pancreatic Cyst. There is a very small risk that an incidental pancreatic cyst may be malignant [8]. For instance, an incidental pancreatic cyst on MRI has a 10 in 100,000 chance of being a mucinous invasive malignancy and a 17 in 100,000 chance of being a ductal carcinoma [8]. The risk of malignant transformation in pancreatic cysts is estimated to be 0.24% per year [9], varying according to histologic subtype [7,10]. Yet there is considerable overlap in the imaging appearance of histologically distinct pancreatic cysts, particularly those <3 cm in size, with over 60% of cysts lacking a specific radiologic appearance on CT or MRI [6]. Another important feature in the natural history of pancreatic cysts is the small risk of pancreatic adenocarcinoma developing at a separate site within the pancreas [4,7,11-13]. Although the risk of cyst-related or concomitant pancreatic malignancy is small, there is a need to characterize incidental pancreatic cysts effectively at initial imaging in order to guide management.


Pancreatic Cyst

Pancreatic Cyst. Appropriate imaging evaluation of incidental pancreatic cysts is critical because morphology determines management. As an example, surveillance is generally recommended for cysts <3 cm in size without worrisome features or high-risk stigmata [7,13]. Cysts with worrisome features undergo sampling with endoscopic ultrasound fine-needle aspiration (EUS-FNA) [8-10] and those with high-risk stigmata are typically resected [8-10]. For management recommendations please refer to the ACR White Paper on Management of Incidental Pancreatic Cysts [7].


Pancreatic Cyst

Pancreatic Cyst. The following recommendations refer to the initial imaging evaluation of pancreatic cysts incidentally detected and incompletely evaluated on imaging studies performed for unrelated indications. The recommendations below apply


Pancreatic Cyst

Pancreatic Cyst. Reprint requests to: publications@acr.org


Pancreatic Cyst

Pancreatic Cyst. Pancreatic Cyst irrespective of the imaging modality in which the cyst was initially detected. CT abdomen, MRI abdomen with MRCP, and US abdomen endoscopic are included in the discussion. These are the three conventional imaging modalities used in the workup of pancreatic cysts. Although we acknowledge the added value of US (especially contrast-enhanced US) in select cases in which workup with conventional imaging is inconclusive or incomplete, US has been omitted from the discussion because it is not routinely used in this setting.


Pancreatic Cyst

Pancreatic Cyst. Discussion of Procedures by Variant Variant 1: Incidentally detected pancreatic cyst less than or equal to 2.5 cm in size. Initial evaluation. CT Abdomen MRI is preferred over contrast-enhanced CT in this setting. The sensitivity and specificity of CT for distinguishing IPMN from other cystic pancreatic lesions is 80.6% and 86.4% compared with 96.8% and 90.8% for MRI [3,18]. Advantages of CT include its ease of implementation and excellent spatial resolution. Multidetector CT provides critical diagnostic information pertaining to the presence or absence of calcifications (both in the background parenchyma and in the cyst proper), ductal dilation, intralesional septations, mural nodules, and pancreatic duct communication [6,15].


Pancreatic Cyst

Pancreatic Cyst. MRI Abdomen with MRCP Contrast-enhanced MRI with MR cholangiopancreatography (MRCP) is considered the procedure of choice in this setting because of its superior soft-tissue contrast and superior ability to demonstrate ductal communication [6-10]. The reported sensitivity of thin-slice 3-D MRCP acquisitions for demonstrating communication of a cyst with the pancreatic duct is as high as 100% [6,22]. Communication with the main pancreatic duct is suggestive of IPMN, although this may also be seen in the setting of pseudocysts [6]. The sensitivity of MRI for detection of internal septations is 91% [6,22], and its diagnostic accuracy for distinguishing between malignant and nonmalignant lesions ranges between 73.2% and 91% [6,23,24]. In distinguishing IPMN from other cystic lesions, studies have reported a sensitivity of 96.8% and a specificity of 90.8% [3,18].


Pancreatic Cyst

Pancreatic Cyst

Pancreatic Cyst. Pancreatic Cyst


Pancreatic Cyst

Pancreatic Cyst. MRI Abdomen with MRCP Because of its superior soft-tissue resolution and noninvasive approach, contrast-enhanced MRI with MRCP is generally favored over CT or EUS-FNA in this setting [6-10]. The diagnostic accuracy of MRI for distinguishing between malignant and nonmalignant lesions ranges from 73.2% to 91% [6,23,24]. Its accuracy at diagnosing the specific type of cyst is slightly lower at 50% [23]. However, an exception may be the distinction of IPMN from other cystic lesions, in which studies have reported a sensitivity of 96.8% and specificity of 90.8% [3,18].


Pancreatic Cyst

Pancreatic Cyst. In a study of over 300 patients with pancreatic cysts, the addition of EUS-FNA to the diagnostic workup significantly altered the management strategy in nearly 72% of patients [28]. Management algorithms integrating clinical data, imaging, and fluid analysis have reported cyst classification sensitivities of 90% to 100% and specificities of 92% to 98% [7,25]. The addition of EUS-FNA to management algorithms combining clinical history and imaging may also reduce unnecessary surgeries by 91% [7].


Pancreatic Cyst

Pancreatic Cyst. Variant 3: Incidentally detected pancreatic cyst greater than 2.5 cm in size. High-risk stigmata or worrisome features. Initial evaluation. CT Abdomen The presence of high-risk stigmata or worrisome features significantly increases the risk of malignancy, and therefore EUS-FNA is favored over CT in this setting [8,9,14]. In cases in which EUS-FNA cannot be performed and the patient is not a candidate for MRI with MRCP, a dual-phase contrast-enhanced pancreatic protocol CT may still be of value for cyst characterization or presurgical planning [1,7-10,13,19-21]. The use of IV contrast improves detection of worrisome features and high-risk stigmata and the assessment of surrounding anatomy [1,7-10,13,19- 21].


Pancreatic Cyst

Pancreatic Cyst. US Abdomen Endoscopic When high-risk stigmata or worrisome features are present, the appropriate initial imaging study is EUS-FNA [7- 10]. The unique advantage of EUS-FNA is its ability to distinguish mucinous from nonmucinous lesions by means of biochemical markers assayed from cyst fluid samples. This facilitates a specific diagnosis in many cases [25,28- 30]. For instance, the presence of nongut mucin supports a diagnosis of mucinous neoplasm. Carcinoembryonic antigen levels <5 ng/mL suggest pseudocyst or serous cystadenoma. A carcinoembryonic antigen threshold level in the range of 192 to 200 ng/mL is 80% accurate for diagnosis of a mucinous cyst [13,29]. Amylase levels of >250 IU/L suggest a pseudocyst. Molecular assays for markers such as K-ras, GNAS, PTEN, VHL, TP53, and PIK3CA may also assist in differentiating neoplastic cystic lesions and predicting cyst behavior. When performed in centers with expertise in EUS-FNA, cytological evaluation can identify atypia, dysplasia, or neoplasia [7,13,25]. Studies have demonstrated that the presence of high-grade epithelial atypia in IPMN detects approximately 30% more cancers than the presence of worrisome imaging features alone [13].


Pancreatic Cyst

Pancreatic Cyst. Variant 5: Follow-up imaging of pancreatic cyst. CT Abdomen The risk of malignant transformation of a pancreatic cyst is approximately 0.24% per year [9]. Once a pancreatic cyst has been characterized on a dedicated baseline examination, subsequent follow-up may be performed with either CT or MRI. There is no evidence to suggest that MRI is superior to CT for detection of new or developing worrisome features or pancreatic ductal adenocarcinoma, and cysts that change at follow up typically do so by increasing size, which is well assessed by either modality [7], although modality concordance between baseline and follow-up examinations may facilitate comparison. For CT follow-up, a dual-phase contrast-enhanced pancreatic protocol CT, including late arterial and portal venous phases, should be performed [7,8].


Pancreatic Cyst

Pancreatic Cyst. The frequency and duration of follow-up is controversial and depends on multiple factors, including patient age, family history of pancreatic ductal adenocarcinoma, cyst size, and whether or not there has been prior surgical resection of a pancreatic cyst. For patients with a nonspecific pancreatic cyst without a history of prior surgery, the surveillance plan will depend upon patient age and the cyst size. Follow-up intervals are generally in the range of 6 months to every 2 years for a minimum of 5 to 10 years [7-9]. Development of high-risk stigmata or worrisome features during the surveillance period should prompt EUS-FNA or surgical evaluation. For patients with a previous history of surgery for IPMN or invasive MCN without residual disease, continued surveillance is recommended, in view of the small yearly risk of pancreatic ductal adenocarcinoma of 0.7% to 0.9% [8]. For patients with known IPMN in the remnant pancreas, residual IPMN at the surgical margins, or new postoperative recurrence of IPMN, surveillance recommendations are less well defined [8]. To date, there is no evidence basis for the recommended size threshold to follow-up cysts. Based on limited clinical and published experience, a cyst <5 mm may require one follow-up CT or MRI at 2 years. Demonstrating stability at 2 years is sufficient to stop surveillance.


Pancreatic Cyst

Pancreatic Cyst. MRI Abdomen with MRCP The risk of malignant transformation of a pancreatic cyst is approximately 0.24% per year [9]. Once a pancreatic cyst has been characterized on a dedicated baseline examination, subsequent follow-up may be performed with either CT or MRI. There is no evidence to suggest that MRI is superior to CT for detection of new or developing worrisome features or pancreatic ductal adenocarcinoma [7], although modality concordance between baseline and follow-up examinations may facilitate comparison.


Pancreatic Cyst

Pancreatic Cyst. The issue of whether IV contrast is necessary for MRI follow-up of pancreatic cysts remains controversial. Noncontrast MRI is associated with shorter scan times, with some sources citing little difference in the ability to detect evolving dysplastic changes compared with a contrast-enhanced study [7,33,34]. However, the use of IV contrast may permit detection of high-risk stigmata such as enhancing mural nodules. An abbreviated protocol MRI, including T2-weighted sequences and dual-phase (late arterial and portal venous phase) contrast-enhanced acquisitions, has been shown to be equivalent to standard pancreatic protocol MRI for detection of evolving dysplasia [7,34].


Pancreatic Cyst

Pancreatic Cyst. The frequency and duration of follow-up is controversial and depends on multiple factors, including patient age, family history of pancreatic ductal adenocarcinoma, cyst size, and whether or not there has been prior surgical resection of a pancreatic cyst. For patients with a nonspecific pancreatic cyst without a history of prior surgery, the surveillance plan will depend upon patient age and the cyst size. Follow-up intervals are generally in the range of 6 months to every 2 years for a minimum of 5 to 10 years [7-9]. Development of high-risk stigmata or worrisome features during the surveillance period should prompt EUS-FNA or surgical evaluation [8,9,14,26]. For patients with a previous history of surgery for IPMN or invasive MCN without residual disease, continued surveillance is still recommended in view of the small yearly risk of pancreatic ductal adenocarcinoma [8]. For patients with known IPMN in the remnant pancreas, residual IPMN at the surgical margins, or new postoperative recurrence of IPMN, surveillance recommendations are less well defined [8]. To date, there is no evidence basis for the recommended size threshold to follow-up cysts. Based on limited clinical and published experience, a cyst <5 mm may require one follow-up CT or MRI at 2 years. Demonstrating stability at 2 years is sufficient to stop surveillance.


Pancreatic Cyst

Pancreatic Cyst. US Abdomen Endoscopic The risk of malignant transformation of a pancreatic cyst is approximately 0.24% per year [9]. Although detection of new or evolving dysplasia may prompt evaluation with EUS-FNA, EUS-FNA is not recommended for routine follow-up of pancreatic cysts because of its invasive approach [7-10]. Patients who undergo EUS-FNA without concerning results may resume surveillance with CT or MRI according to the recommendations for cysts without high-risk stigmata or worrisome features [7-9].


Pancreatic Cyst

Pancreatic Cyst. 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.


Pancreatic Cyst

Pancreatic Cyst. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.