Imaging of the Axilla

Imaging of the Axilla. A small single-center study looking at the role of midtreatment axillary US in 159 patients of mixed breast cancer subtypes observed that US performed better for residual axillary nodal tumor burden than for residual index breast cancer and provided more consistent results across different cancer subtypes [109]. Variant 8: Female. Breast cancer, greater than 2 cm in size, clinical node-negative. Imaging of the axilla after completion of neoadjuvant chemotherapy. NAC is used to treat operable large tumors, nonoperable locally advanced tumors, and inflammatory breast cancers prior to definitive surgical management. If there is pathological response to NAC and the patient is clinically node- negative, SLNB is preferred over ALND in order to minimize morbidity. In a study of 925 patients treated with NAC, 5-year overall survival was superior for patients with pathologic complete remission of cytological proven axillary lymph node metastases (93%) compared with those without complete response (72%) [110]. The prognostic significance of response to NAC can vary between the primary breast tumor and the axilla and based on tumor receptor subtypes (eg, triple negative versus HER2 positive cancers) [112]. Those patients with initial node-positive breast cancer who achieve complete pathological response after NAC have similar prognoses as to those with clinical node-negativity [112]. Even though no imaging will replace SLNB or ALND for staging, the ability to assess response during or after NAC helps to predict outcomes and aids with treatment planning. CT Chest, Abdomen, and Pelvis There is no relevant literature to support the use of contrast-enhanced or noncontrast-enhanced CT to image the axilla after completion of NAC. Digital Breast Tomosynthesis Diagnostic There are no data to support the use of DBT to image the axilla after completion of NAC in patients with initial clinical node-negative disease and no new clinical concern or palpable axillary lump.


Imaging of the Axilla

Imaging of the Axilla. For assessment of the primary breast tumor, one prospective study of 51 stage II and III breast cancer patients reported that MRI and DBT outperformed mammography and whole-breast US in the prediction of pathologic complete response [113]. However, this study cannot be extrapolated to axillary nodal disease. FDG-PET/CT Skull Base to Mid-Thigh There are limited data to support the use of FDG-PET/CT for assessing response of nodal disease from breast cancer following completion of NAC. Most studies report changes in size and SUV measurements of the index breast carcinoma or distant metastases. Four meta-analyses of FDG-PET/CT in detecting residual breast disease reported a pooled sensitivity of 81% to 84% and a specificity of 66% to 79% [114-118]. FDG-PET/CT is limited by the lack of consensus for standard criteria to measure response of the index tumor or nodal disease, and SUV measurements underestimating the amount of residual disease when the residual tumor size is small. In one meta-analysis, 4 of 19 studies reported a pooled sensitivity of 92% and an NPV of 88% in predicting regional lymph node response but the specificity was inconclusive [118]. Even though there is suggestion that the early changes in SUV may correlate Imaging of the Axilla with NAC response, a negative FDG-PET/CT does not guarantee that the final pathology is also negative, especially if the residual tumor is of low to moderate grade [119,120]. A recent report from the National Cancer Database of 33,162 patients concluded that a breast-only response from a node-only response or both breast and nodal response had different prognoses, which also varied with tumor subtypes [112]. Given the limited data, FDG-PET/CT is not currently performed post-NAC to restage the axilla. Mammography Diagnostic Mammography can reliably be used to assess response of a primary breast malignancy to NAC. However, it is less useful in assessing axillary nodal response to therapy given that the axilla is incompletely visualized.


Imaging of the Axilla

Imaging of the Axilla. MRI Breast The role of breast MRI in detecting residual tumor within the axillary lymph nodes remains questionable [121]. Based on a 26-study meta-analysis, MRI has moderate sensitivity (77%) and specificity (90%) for detecting residual disease after NAC [122,123]. Most of the literature confirms the superiority of MRI in detecting residual tumor within the breast after NAC compared with mammography, US, and physical examination [124]. However, it is not proven that preoperative MRI is associated with improved surgical outcomes or lower recurrence rates [125]. A meta-analysis of 44 studies reported MRI sensitivity for detecting residual disease in the breast was 92% and a specificity of 90% [124]. MRI also demonstrates higher accuracy in triple negative tumors and HER2-positive tumors [126-128]. The performance of MRI for the primary breast lesion cannot be extrapolated into MRI performance of the axillary nodal disease [112]. Therefore, MRI is not used routinely for predicting response of axillary nodal disease. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for assessing response after treatment with NAC. US Axilla The role of axillary US to assess the axilla after NAC remains controversial [7]. Most of the data from multicenter trials involve patients with initial clinical node-positive disease [129,130]. These studies, evaluating SLNB after NAC, report that the accuracy rates of SLNB are acceptable. With the variable sensitivity and specificity of axillary US, even in combination with percutaneous biopsy, axillary US is not able to replace SLNB. Therefore, axillary US may not assess axillary response after chemotherapy. Variant 9: Female. Breast cancer, greater than 2 cm in size, clinical node-positive. Imaging of the axilla after completion of neoadjuvant chemotherapy and prior to surgery. NAC is used to treat operable large tumors, nonoperable locally advanced tumors, and inflammatory breast cancers prior to definitive surgical management.


Imaging of the Axilla

Imaging of the Axilla. Information on the residual disease or positive axillary nodes after NAC is beneficial for the determination of the axillary surgical management and for the need of radiation therapy [7]. The guidelines define low tumor burden in the axilla as nodal disease that is image-detected disease not apparent on clinical examination; however, the imaging test is not specified in the guidelines. If there is pathological response to NAC and the patient is clinically node-negative, SLNB is preferred over ALND in order to minimize morbidity. In a study of 925 patients treated with NAC, 5-year overall survival was superior for patients with pathologic complete remission of the cytological proven axillary lymph node metastases (93%) compared with those without complete response (72%) [110]. Imaging of the Axilla CT Chest, Abdomen, and Pelvis There are no relevant data to support the use of contrast-enhanced or noncontrast-enhanced CT to image the axilla after completion of NAC. Digital Breast Tomosynthesis Diagnostic There are no data to support the use of DBT to image the axilla after completion of NAC in patients with initial clinical node-positive disease pre-NAC and who have no clinical suspicion of disease progression or new axillary nodal disease. When comparing mammography to DBT, one prospective study of 51 stage II and III breast cancer patients reported that MRI and DBT outperformed mammography and whole-breast US in the prediction of pathologic complete response [113]. Unfortunately, this cannot be extrapolated to axillary nodal disease because DBT does not completely visualize the entire axilla. DBT may be useful in selected cases after NAC because it may identify response within a clipped node and provide a means for image guided localization [131]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is widely used to assess response to therapy, despite the lack of consensus on the criteria for determining response.


Imaging of the Axilla

Imaging of the Axilla. The reported pooled sensitivity for FDG-PET/CT is 71% to 88% and specificity is 69% to 79.3% [117,120,132,133]. Most of the studies do not specifically report on response of the regional lymph nodes. In one meta-analysis of four studies involving 920 patients, the sensitivity of FDG-PET/CT for regional lymph node response assessment is 92% [118]. In another meta-analysis of 987 abstracts, only four were eligible for analysis, yielding a PPV between 40% and 100% [134]. The timing of FDG-PET/CT is critical and varies between studies, with some investigators demonstrating FDG- PET/CT has more accuracy during NAC (after first or second cycles of chemotherapy) than after NAC, whereas MRI performed better at the end of NAC [118,133]. MRI had higher sensitivity in predicting the pathologic response after NAC in 13 studies involving 575 patients, and FDG-PET/CT had a higher specificity in these same 13 studies involving 618 patients [132]. Currently, there is lack of consensus that early response detected by imaging tests translates into improved overall outcomes. A negative FDG-PET/CT during or after NAC does not necessarily correlate with final pathological node-negative disease, as demonstrated in one series of 206 patients [119]. SUV values may underestimate or overestimate response when the residual tumor is small. Some investigators have reported SUVmax <2.5 as negative [120], whereas others demonstrated that the change in SUV before and after NAC or change between the pre-NAC FDG-PET/CT examination and the examination performed after the first or second cycle of NAC were better predictors of response [134-136]. Despite the research, there is no accurate noninvasive test to replace SLNB or ALND at this time. However, one benefit of using FDG-PET/CT is that this examination can also evaluate other sites of metastases in a single study [102]. A search for a noninvasive restaging technique for identifying patients with axillary complete response is ongoing.


Imaging of the Axilla

Imaging of the Axilla. Mammography Diagnostic Mammography can reliably be used to assess response of a primary breast malignancy to NAC. However, it is less useful in assessing axillary nodal response to therapy given that the axilla is incompletely visualized. MRI Breast In patients who have had axillary nodal metastatic disease diagnosed prior to NAC for breast cancer, there is little consensus on how to image the axilla subsequently. MRI has some limitations in evaluating the axilla and is unlikely to be the sole imaging test for estimating residual tumor burden preoperatively [121]. However, a combination of tests with axillary US, MRI, or FDG-PET/CT may be the future direction for clinical trials trying to answer such questions (https://clinicaltrials.gov/ct2/show/NCT03188393). At least one study suggests that measurements at 360 seconds after contrast administration provides the most accurate measurements of size, compared with the earlier phase or the later phase of the dynamic series [137]. Imaging of the Axilla Most of the literature focuses on the evaluation of response of the primary breast tumor after NAC and MRI superiority to mammogram, US, and physical examination in this setting [124]. The performance of MRI for the primary breast lesion cannot be extrapolated to MRI performance of the axillary nodal disease [112]. Therefore, MRI is not used routinely for predicting response of axillary nodal disease. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for assessing response after treatment with NAC. US Axilla Because of its noninvasive nature, axillary US may evaluate for residual axillary nodal disease despite its PPV of 60% to 81%, NPV of 43% to 74%, and specificity of 37% to 92% [138]. However, the sensitivity of US (71%) for prediction of residual nodal metastatic disease was higher than that of clinical examination and MRI/PET in most studies [139].


Imaging of the Axilla

Imaging of the Axilla. Limited data have suggested that the sensitivity of axillary US is higher for some subtypes such as triple negative breast cancer (69%) and HER2 positive breast cancer (71%) [140,141]. This discussion is based on the understanding that patients post-BCS or postmastectomy with reconstruction have likely already undergone a diagnostic mammogram or DBT to evaluate for or rule out in-breast recurrent disease. Therefore, the possible next imaging test or initial imaging test for the axilla are discussed below for each modality. Imaging of the Axilla CT Chest, Abdomen, and Pelvis There are no data to support the utilization of CT for axillary node assessment in the setting of newly diagnosed in- breast recurrent disease or as the initial imaging test for the axilla. However, CT can be performed concurrently at the time of the locally recurrent breast cancer diagnosis to rule out distant metastatic disease and for pretreatment planning. CT allows visualization of any chest wall involvement as well as the relationship of the recurrent disease to regional vital structures such as axillary artery and vein [7,92,154]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT may be ordered concurrently at the time of the locally recurrent breast cancer diagnosis to rule out distant metastatic disease and for pretreatment planning. PET/CT is helpful in identifying unsuspected regional nodal disease or distant metastases in certain situations such as in patients with locally advanced breast cancer and inflammatory breast cancer [7]. In a meta-analysis of 26 studies involving 1,752 patients with suspected recurrent breast cancer, the pooled sensitivity for FDG-PET/CT was 90% and specificity was 81%; FDG-PET/CT is more accurate than PET alone [155]. The authors noted that the studies were heterogeneous, and therefore the analysis had limitations. In-breast recurrent disease versus chest wall or nodal recurrent disease was not specified [155].


Imaging of the Axilla

Imaging of the Axilla. MRI Breast Breast MRI is a highly sensitive imaging modality for assessing disease within the breast [156,157]. There are no data to support breast MRI as the initial imaging test of the axilla in patients with newly diagnosed locally recurrent breast cancer to evaluate for additional nodal disease. The MRI may be ordered after the mammogram or DBT to evaluate additional recurrent disease or disease extent within the breast not completely seen on mammogram or DBT [158]. An observational cohort study of 13,266 women and a single-center study of 1,521 women reported higher cancer detection rate with MRI compared with mammography [156,157]. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for imaging the axilla in patients with newly diagnosed recurrent disease. US Axilla US can be used to evaluate the axilla in patients with newly diagnosed recurrent breast cancer after BCS, after mastectomy, or with suspicion of recurrent nodal disease in the axilla. Diagnostic mammogram and/or DBT to evaluate for in-breast recurrent disease has also been shown to be helpful [154]. Axillary US can also provide guidance for percutaneous biopsy of any suspicious nodes because it influences potential surgical approach (SLNB versus full ALND). Variant 11: Female. Suspicious axillary node on mammography or ultrasound. Next imaging study. CT Chest, Abdomen, and Pelvis CT is not frequently used to assess abnormal axillary nodes detected on US or mammography; however, it is often used to evaluate a biopsy-proven nonbreast malignant axillary node. One study with 297 patients from two centers found no change in the number of second axillary surgeries between patients who received a CT scan of their axilla versus those who did not [47]. There are little data to support the use of contrast- or noncontrast-enhanced CT for this indication if there is no clinical suspicion of additional systemic disease.


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh Less than 1% of breast cancers initially present as axillary adenopathy [32,33]. Historically, mammography, US, and breast MRI have helped to identify the primary malignancy in patients with pathologic axillary adenopathy from unknown primary. However, mammography and US have relatively low sensitivity for detecting the primary breast lesion [31,159]. The addition of breast MRI has improved sensitivity [160] because MRI is able to detect the primary breast lesion in 36% to 86% of cases [39]. Although PET/CT can be helpful in identifying the site of an unknown primary, for breast cancer, there are little data to support its routine use. MRI Breast Once the suspicious axillary node has been documented as metastatic nodal disease, then breast MRI can detect a mammographic or sonographic occult breast lesion with high sensitivity for detecting an in-breast lesion or confirm no breast primary [34,35]. In a meta-analysis of 8 retrospective studies involving 220 patients, MRI detects an occult breast cancer in 72% of cases with a pooled sensitivity of 90% and a specificity of 31% [39]. MRI can also help further characterize the axillary mass by evaluating its relationship to adjacent vessels, the chest wall, and other axillary structures. In a meta-analysis of 26 studies looking at the diagnostic performance of MRI in detecting Imaging of the Axilla metastatic nodal disease, the pooled sensitivity and specificity in patients with breast cancer is 77% and 90%, respectively [123]. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for imaging the axilla in patients with suspicious axillary nodes detected on mammography and US. US-Guided Core Biopsy Axillary Node US-guided biopsy (either core needle biopsy or FNA) may provide a diagnosis for morphologically abnormal lymph nodes detected on imaging.


Imaging of the Axilla

Imaging of the Axilla. In a meta-analysis of 1,353 patients from 6 studies, US-guided core needle biopsy was superior to US-guided FNA in diagnosing axillary nodal metastases with reported pooled sensitivity of 88% versus 74%, respectively. Both US-guided core needle biopsy and FNA had a high specificity of 100% [86]. Complications such as pain, hematoma, and bruising were higher with core needle biopsy than FNA. US-Guided Fine Needle Aspiration Biopsy Axillary Node US-guided FNA biopsy is a reliable procedure associated with minimal complications. In a meta-analysis of 31 studies, US-guided FNA improved the median sensitivity of US from 61% to 79% and specificity from 82.0% to 100% [62]. In another publication of 3,781 breast cancer patients, the sensitivity and specificity of axillary US alone were 59% and 89%, respectively. The specificity improved to 100% when axillary US was combined with FNA. FNA resulted in sensitivity, specificity, PPV, NPV, and accuracy of 52%, 100%, 100%, 74.8%, and 80%, respectively [63]. The decision to perform FNA or core biopsy of a suspicious axillary node is not standardized and depends on provider choice and patient factors. Variant 12: Female. Suspicious axillary node on any other imaging modality (excluding mammography and ultrasound). Next imaging study. Digital Breast Tomosynthesis Diagnostic When a suspicious lymph node is identified on imaging, correlation with clinical history and physical examination is essential to guide management. If a breast primary is of concern, mammography and DBT can assist in identifying the breast primary. At least one study has shown that DBT is superior to full-field digital mammography for detection of subtle architectural distortion [161]. Mammography Diagnostic When a suspicious lymph node is identified on imaging, other than mammography or DBT, correlation with clinical history and physical examination is essential to guide further imaging.


Imaging of the Axilla

Imaging of the Axilla. If a breast primary is of concern, mammography and/or DBT may assist in identifying a primary breast malignancy. Mammography is not optimal for evaluating the axilla. Valente et al [162] found that mammography has a high FNR in the detection of axillary metastatic lymphadenopathy. US Axilla If mammogram or DBT identifies a primary breast malignancy, then axillary US after mammogram and/or DBT may evaluate the nodal size, nodal cortical, and hilar morphology. The sensitivity and specificity for axillary US for differentiating benign from malignant nodes is variable, with reported sensitivity ranging from 26% to 94% and specificity from 53% to 98% [58]. Axillary US alone has relatively low NPV and sensitivity and therefore is not a reliable predictor of axillary nodal burden [83,84]. When combined with needle biopsy, however, the sensitivity improves from 61% to 79% in a meta-analysis of 21 studies [54,62,85]. Some US features that are more likely to be associated with malignancy include short-axis diameter >1 cm, cortical thickness >0.3 cm, and absence of a fatty hilum [87-90]. The absence of a fatty hilum has the highest PPV (90% to 93%) for malignancy [103,104]. A suspicious node on US warrants percutaneous biopsy because a positive axillary US helps to identify those patients at risk for higher tumor burden [54,55]. However, a negative axillary US with or without biopsy does not rule out nodal disease [58]. US-Guided Core Biopsy Axillary Node Based on a meta-analysis of 1,353 patients with newly diagnosed breast cancer, US-guided core needle biopsy is superior to US-guided FNA with a reported sensitivity of 88% for core biopsy and 74% for FNA [86]. The overall sensitivity of US-guided biopsy ranges from 52% to 90%, whereas the specificity ranges from 98% to 100% [59- 63]. Imaging of the Axilla


Nonatherosclerotic Peripheral Arterial Disease.  Introduction/Background Lower-extremity vascular diseases span a diverse range of etiologies and may be autoimmune, congenital, degenerative, inflammatory, infectious, metabolic, neoplastic, or traumatic in nature. Examples of such conditions include, but are not limited to, aneurysm formation, atherosclerosis, Buerger disease, cystic adventitial disease, dissection/transection, deep vein thrombosis, external iliac artery endofibrosis (EIAE), fibromuscular dysplasia (FMD), popliteal arterial entrapment syndrome (PAES), segmental arterial mediolysis (SAM), and genetic syndromes such as Marfan syndrome (MS), Loeys-Dietz syndrome (LDS), and vascular Ehlers-Danlos syndrome (EDS). Because of the plethora of potential underlying disease processes, imaging is often employed to secure a diagnosis and assist in guiding clinical management. Accurate vascular imaging relies upon visualization of the vessel lumen, vessel wall, and surrounding soft-tissue structures, with some modalities also offering the ability to characterize blood flow direction and velocity. Furthermore, nonvascular findings are often paramount in supporting a suspected clinical syndrome [1-4] or guiding surgical management [5-8]. Guidelines proposed in this document focus on nonatherosclerotic, arterial lower-extremity vascular disease. PAES is the most common cause of surgically correctable lower-extremity vascular insufficiency in young adults and consists of anatomic and functional subtypes. Patients with PAES present with calf claudication, paresthesia, and swelling during exercise. In anatomic PAES (Types I, II, III, and V), the extravascular structures within the popliteal fossa compress the popliteal artery and/or the popliteal vein, which results in compression and stenosis or occlusion during plantar flexion. Functional PAES (Type IV) results in compression of the popliteal artery despite the presence of an anatomically normal popliteal fossa; its etiology remains unclear.


Nonatherosclerotic Peripheral Arterial Disease. Either subtype may lead to aneurysm or pseudoaneurysm formation, thrombosis or distal thromboembolism [5-8,15-19]. EIAE is a rare cause of performance-limiting claudication that occurs primarily in endurance athletes. Although EIAE typically occurs in cyclists, it has been described in other groups of elite endurance athletes. Symptoms include lower-extremity weakness, thigh pain, and symptom resolution after cessation of exercise [20]. Its etiology is poorly understood and may be multifactorial. Suggested mechanisms include repeated mechanical Reprint requests to: publications@acr.org Nonatherosclerotic Peripheral Arterial Disease trauma upon the external iliac artery by a hypertrophied psoas muscle during hip flexion with subsequent arterial kinking [21] and vasospasm [22]. Arterial-brachial pressure indexes typically decrease following exercise [20]. Connective tissue diseases are multisystem disorders, several of which profoundly involve the vascular system. MS is an autosomal-dominant (AD) connective tissue disorder caused by a mutation in the FBN1 gene that codes for fibrillin-1 and occurs in 1 in 20,000 individuals. The systems typically affected by MS are cardiovascular, ocular, and skeletal. MS is classically associated with aortic root aneurysms and dissection; however, the dissection flap may extend into the iliac arteries resulting in pain, pallor, paresthesias, and pulselessness [1,24]. LDS results from an AD heterozygous mutation in either of the genes that encode transforming growth factor beta. LDS has a much more aggressive clinical course than MS, with a mean survival of 26 years. Like MS, LDS is associated with aortic root aneurysm and dissection [3]. Vascular EDS, formerly known as EDS type IV, is an AD disease caused by a heterozygous mutation in the COL3A1 gene that encodes type III collagen. Vascular EDS can affect any vessel and carries a poor prognosis that is due to risk of life-threatening arterial rupture [4].


Nonatherosclerotic Peripheral Arterial Disease. SAM is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects the visceral abdominal vessels, although involvement of the iliac arteries has been reported [27]. Lysis of the medial layer of the arterial wall in SAM results in dissection, stenosis, occlusion, or aneurysm formation; it commonly presents with catastrophic hemorrhages within the abdominal cavity or retroperitoneum as a result of spontaneous aneurysm rupture [28-30]. Cystic adventitial disease is a rare vascular disease predominantly affecting healthy young men with no cardiovascular risk factors. Arterial involvement is more common than venous involvement, with most cases seen involving the popliteal artery. Cystic adventitial disease affecting the lower extremity typically results in claudication or pain of sudden onset, while imaging demonstrates adventitial cysts localized to the site of symptomatology. Surgical resection is usually curative thereby obviating follow-up [31]. Injury to the lower-extremity vasculature is not an uncommon occurrence in the setting of penetrating or blunt trauma. Rapid diagnostic imaging is paramount to exclude or confirm vascular injury in these potentially unstable individuals. Discussion of Procedures by Variant Variant 1: Suspected popliteal entrapment syndrome. Initial imaging. CTA Lower Extremity CT angiography (CTA), including multiplanar reformation and 3-D volume-rendered reconstructions, is helpful in depicting popliteal vascular changes (vessel deviation, stenosis, occlusion, aneurysm formation) and abnormal musculotendinous structures in the setting of PAES [5,19]. Following revascularization for PAES, CTA is recommended to assess graft patency after an abnormal ultrasound (US) [17]. The use of dynamic CTA has also been proposed for the initial workup of PAES, as images of both lower extremities can be obtained at both rest and plantar flexion in a single examination requiring only one contrast bolus [15].


Nonatherosclerotic Peripheral Arterial Disease. However, MRA and US duplex Doppler are typically preferred because they do not require ionizing radiation. MRA Lower Extremity MR angiography (MRA) can be used to evaluate vascular abnormalities and the dynamic changes in the popliteal artery during plantar flexion [16]. MRA is typically performed as a confirmatory test after US duplex Doppler. However, many patients are unable to maintain steady forced plantar flexion throughout the duration of lengthy MR sequences, resulting in excessive motion and degradation of image quality [7,8,15]. Despite this, a recent Nonatherosclerotic Peripheral Arterial Disease study demonstrated superiority of MRA over digital subtraction angiography (DSA) in confirming PAES [6]. MRA can be particularly helpful in defining abnormal musculotendinous structures. Furthermore, the T1- weighted and T2-weighted sequences done as part of the MRA study are currently the gold standard for defining the complete anatomy of the popliteal fossa and are therefore most appropriate for determining the anatomic abnormality in suspected PAES [7,15]. MRA without intravenous (IV) contrast is typically not used because the long acquisition times required cause challenges for their performance during stress maneuvers. However, the anatomic imaging used to determine the etiology of PAES can be done without IV contrast. Arteriography Lower Extremity Selective arteriography is regarded as the gold standard in identifying dynamic arterial deviation and/or occlusion during plantar flexion in addition to identifying vascular occlusion/stenosis, aneurysm, and thrombosis. [5,7,15]. In addition to being an invasive modality, arteriography is limited by its inability to depict extravascular anatomy. One study comparing the use of DSA and MRI in the evaluation of PAES found DSA to be nonspecific and unable to determine the etiology of patient symptoms [6], thereby obviating the need for cross-sectional imaging.


Nonatherosclerotic Peripheral Arterial Disease. Selective arteriography is therefore often used as a confirmatory modality when PAES is suspected on cross- sectional imaging or US [7,16]. US Duplex Doppler Lower Extremity US duplex Doppler is heavily relied upon in the initial workup of PAES, where real-time visualization of flow occlusion and changes in segmental Doppler pressures upon provocative plantar flexion is crucial in confirming a suspected diagnosis [16,18]. This is extremely beneficial in the setting of functional PAES, where lack of an anatomic abnormality limits the sensitivity of cross-sectional modalities like CTA and MRA [18]. In PAES patients treated with popliteal bypass, US duplex Doppler is the first-line modality of choice in assessing graft patency; CTA, MRA, and selective arteriography are reserved for postoperative patients with abnormal US duplex Doppler examinations [17]. Several studies have found the use of US in the diagnosis of PAES to be potentially problematic, as the necessary use of transducer pressure applied during the examination may result in velocity changes that are difficult to interpret [7]. Provocative maneuvers may also shift the popliteal artery out of the Doppler region of interest, giving the artifactual appearance of occlusion [7,8]. US duplex Doppler has been found to have a particularly high false-positive rate in the workup of PAES, especially in athletes [5]. MRA is recommended to confirm the etiology of PAES in patients with a positive US duplex Doppler study and in patients with a negative US duplex Doppler study with a high index of clinical suspicion. US Intravascular Lower Extremity The use of intravascular US (IVUS) has been reportedly beneficial in confirming and assessing extent of popliteal artery compression in PAES. IVUS is often used as a confirmatory modality when PAES is suspected on cross- sectional imaging.


Nonatherosclerotic Peripheral Arterial Disease. One study lauded IVUS for its ability to evaluate the arterial lumen for intimal change and potential irreparable mural damage that may be missed with conventional US [16]. In functional PAES, IVUS is beneficial in determining the magnitude of extrinsic muscular compression [16]. Variant 2: Suspected external iliac artery endofibrosis. Initial imaging. CTA Lower Extremity CTA is uncommonly used in the diagnosis of EIAE and has not demonstrated diagnostic superiority to MRA combined with US [21]. CTA allows assessment of arterial kinking, arterial wall thickening, stenosis, and extent of involved arterial segment. MRA Lower Extremity The superior contrast resolution inherent to MRA allows for optimal visualization of extravascular anatomy in suspected EIAE. Like CTA, MRA allows assessment of arterial length and kinking, albeit with improved soft- tissue characterization. MRA is less sensitive than US for detecting intravascular lesions. MRA has proven useful in diagnosing EIAE when used in conjunction with US, a combination that was found to be superior or equal to CTA alone [21]. US Duplex Doppler Lower Extremity The ability to visualize changes in both flow dynamics and vessel caliber in real time has been paramount in diagnosing EIAE in endurance athletes [21,22]. Dynamic use of US duplex Doppler and segmental Doppler pressures in both hip flexion and extension can accurately depict flow disturbance [21], while its use pre- and Nonatherosclerotic Peripheral Arterial Disease postexercise may demonstrate associated exercise-induced vasospasm [20,22]. US duplex Doppler has been found to be superior to MRA in detecting intravascular lesions; however, its sensitivity may be limited in patients with only mildly symptomatic disease [21]. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of EIAE. Arteriography Lower Extremity The role of DSA in the evaluation of EIAE is not as well established.


Nonatherosclerotic Peripheral Arterial Disease. The most frequent finding of EIAE at DSA is smooth, long, and eccentric stenosis, with thrombosis and dissection present less frequently [1]. Although the external iliac artery is most frequently affected, the common iliac artery can be involved in approximately 15% of patients [32]. A benefit of arteriography, relative to other modalities, is that the pressure gradient across the narrowing can be measured at baseline as well as during various maneuvers, including following the administration of vasodilators [33]. Acquiring images during hip flexion frequently reveals a kink in the iliac arteries at the site of stenosis [32]. Variant 3: Suspected or known lower-extremity inflammatory vasculitides. Initial imaging. CTA Lower Extremity While the spatial resolution of CTA is relatively high, some authors have suggested that it may not be sensitive enough to resolve the fine collateral vessels seen in thromboangiitis obliterans and other small-vessel pathologies [2]. Evaluation of subtle vascular findings may also be limited by beam hardening artifact related to adjacent bone or metal [34]. CTA is helpful in identifying vessel wall thickening, stenosis, occlusion and collaterals when large- or medium-sized vessels of the lower extremities are involved. MRA Lower Extremity MRA has lower spatial resolution than CTA, a factor that makes it less than ideal in adequately characterizing distal small vessels. Despite this, additional sequences acquired during an MRA examination may be helpful in evaluating for associated nonvascular findings, such as osteomyelitis or septic arthritis [2]. The sensitivity for detecting these soft-tissue abnormalities is greater with contrast-enhanced MRA than noncontrast-enhanced MRA. Arteriography Lower Extremity Because of its high inherent spatial resolution, selective arteriography with DSA is considered the gold standard in the diagnosis of thromboangiitis obliterans [2].


Nonatherosclerotic Peripheral Arterial Disease. US Duplex Doppler Lower Extremity US duplex Doppler can identify the typical corkscrew collateral vessels in the walls of the lower-extremity vessels in patients with thromboangiitis obliterans [35]. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of lower-extremity inflammatory vasculitides. Variant 4: Suspected or known dissection or connective tissue lower-extremity vascular diseases. Initial imaging. CTA Lower Extremity CTA is highly recommended in the workup of MS, LDS, and vascular EDS, as it offers comprehensive whole- body imaging and high spatial resolution in a single study. This allows for evaluation of the entire vascular system and identification of typical musculoskeletal malformations that may assist in the initial diagnosis of a heritable connective tissue disease [1,3,4]. CTA is valuable for defining the true and false lumen and can be used for longitudinal follow-up. Although the initial diagnosis of these diseases is most commonly made in the pediatric population, this document addresses imaging in adults (18 years of age and older) only. Because of the high risk of vascular complications inherent to LDS and MS, CTA surveillance is recommended at least every 1 year [3] and 2 years [1], respectively. MRA Lower Extremity MRA has been suggested for evaluation of the lower extremities in patients with connective tissue disorders, such as MS, LDS, and vascular EDS. However, the lower spatial resolution inherent to MRA limits the evaluation of small arterial branches [1,2,36] compared to CTA. Nonatherosclerotic Peripheral Arterial Disease Arteriography Lower Extremity Given its invasive nature, the use of selective arteriography should be avoided in patients with congenitally weakened vessels (eg, collagen vascular diseases, such as vascular EDS) where the risk of catastrophic vascular perforation is high [1,4].


Nonatherosclerotic Peripheral Arterial Disease. In such patients, it has been suggested that this modality only be performed if it is part of a planned interventional procedure (eg, coil embolization of remote bleeding arteries, etc) [4]. US Duplex Doppler Lower Extremity There is no relevant literature regarding the use of US duplex Doppler in the evaluation of lower-extremity connective disease. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of lower-extremity connective disease, but the same concerns regarding arterial puncture would apply. Variant 5: Suspected or known other noninflammatory lower-extremity vascular diseases (such as fibromuscular dysplasia, segmental arterial mediolysis). Initial imaging. CTA Lower Extremity While selective arteriography is considered the gold standard in diagnosing FMD, CTA has proven helpful in the initial diagnosis and follow-up of FMD within the lower extremities [25,37]. Because of its high spatial resolution, several studies have demonstrated the superiority of CTA over MRA in visualizing vascular lesions in FMD [4,36]. Despite this, one study found CTA to have limited sensitivity in the evaluation of small vessels in patients with mild FMD [36]. CTA may be helpful in the workup of cystic adventitial disease [31]. It has also been advocated as a first-line imaging study in the diagnosis of SAM [28,29] with follow-up recommended at 1- year intervals [27]. MRA Lower Extremity The improved contrast resolution inherent to MRA renders superior characterization of the extravascular soft tissues. This is of particular importance in the workup of cystic adventitial disease, where T1-weighted and T2- weighted sequences may demonstrate connections between adventitial cysts and the adjacent joint capsule. It has been recommended as the modality of choice in preoperative planning for cystic adventitial disease [31]. MRA has also been found useful for annual follow-up in SAM [27].


Nonatherosclerotic Peripheral Arterial Disease. Arteriography Lower Extremity Because of its high inherent spatial resolution, selective arteriography with DSA is considered the gold standard in the diagnosis of FMD [25,26,36,38-40], with many authors claiming that CTA and MRA may lack the spatial resolution necessary to detect small-artery pathology [36]. Arteriography is susceptible to standing waves. Therefore, caution must be exercised to accurately distinguish standing waves from true arterial beading characteristic of FMD [15]. This modality may simultaneously be therapeutic in FMD, as angioplasty is currently the preferred treatment of choice [25,38,39]. Selective arteriography is considered the reference standard in the diagnosis of SAM while also having therapeutic potential [28]. US Duplex Doppler Lower Extremity A recent study found US duplex Doppler to be helpful in diagnosing cystic adventitial disease, where numerous anechoic cysts are seen scattered throughout the adventitia at a site of vessel stenosis [31]. While much has been published about the use of US duplex Doppler in renal artery FMD, no literature is currently present to support its use in the diagnosis of FMD affecting the lower-extremity arteries. US Intravascular Lower Extremity IVUS has been reported to be useful in diagnosing cystic adventitial disease [31]. In FMD, other authors have concluded that IVUS is likely more accurate than other modalities in characterizing the hemodynamic severity of encountered stenosis [39,41]. Variant 6: Lower-extremity vascular trauma. Initial imaging. CTA Lower Extremity CTA is considered especially important in the setting of trauma to the lower extremities. Several studies recognize its use as a first-line investigation in all patients with suspected vascular injury [42], demonstrating a sensitivity of 95% to 100% and a specificity of 87% to 100% [34,43]. Sensitivity for vascular injury in equivocal cases can be increased by using reconstructed images.


Nonatherosclerotic Peripheral Arterial Disease. The use of CTA is associated with lower morbidity than that of selective arteriography and has resulted in a precipitous decrease in negative surgical exploration rates in the post-traumatic Nonatherosclerotic Peripheral Arterial Disease patient [43]. One study has suggested that the critical time saved by CTA in diagnosing lower-extremity vascular injury translates to decreased morbidity, thereby reducing hospital costs while improving outcomes [34]. MRA Lower Extremity MRA is not indicated after trauma, as long requisite imaging times are precarious in a potentially unstable patient. Underlying shrapnel or bullet fragments pose significant safety concerns within the confines of the magnetic field, in addition to degrading image quality [43]. Arteriography Lower Extremity Arteriography is recommended for vascular evaluation in patients with hard signs of vascular injury requiring immediate repair [44,45]. This can be done in the operating room with a C-arm or in a hybrid suite [44,45]. Selective arteriography is invasive and unable to depict extravascular anatomy [34]. In addition, it is time- consuming and could delay treatment of other traumatic injuries. However, it accurately detects active bleeding, pseudoaneurysms, arteriovenous fistula, and vascular thrombosis. A recent retrospective review advocates the use of arteriography if CTA is equivocal [43]. US Duplex Doppler Lower Extremity While portability and lack of nephrogenic contrast administration make US duplex Doppler an attractive option for evaluating the lower-extremity vessels after trauma, significant injury to the superficial soft tissues may limit its accuracy in assessing vascular integrity [43]. A recent meta-analysis reported that the post-test probability of arterial injury was 89% with a positive US and 5% with a negative US [46]. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of lower-extremity vascular trauma.


Indeterminate Renal Mass

Indeterminate Renal Mass.  Introduction/Background Renal masses are increasingly detected in asymptomatic individuals as incidental findings. Many of these are small renal tumors that vary widely in biological aggressiveness, ranging from benign tumors to high-grade renal cell carcinomas (RCCs). An indeterminate renal mass cannot be diagnosed confidently as benign or malignant at the time it is discovered. Masses that can be definitively characterized on the first imaging test will not be discussed in this review. Special Imaging Considerations Dual-energy CT and contrast-enhanced ultrasound (CEUS) are gaining traction in the characterization of indeterminate renal masses. Several studies have demonstrated that dual-energy CT can improve the differentiation between nonenhancing cysts and low-level-enhancing tumors [8-11]. Dual-energy CT with reconstruction of virtual monochromatic images has been shown to decrease or overcome renal cyst pseudoenhancement [12]. Other studies have shown that dual-energy CT can differentiate between solid tumors and hyperdense cysts incidentally detected on a single-phase postcontrast CT [13-15] and can be useful when a comprehensive multiphase renal protocol CT is not available. CEUS with microbubble agents is a useful alternative for characterizing renal masses, especially for patients in whom iodinated CT contrast or gadolinium-based MRI contrast is contraindicated. The microbubble agents are not excreted by the kidneys and therefore do not affect renal function. CEUS allows real-time evaluation of microvasculature and has been shown to be valuable for differentiating between cystic and solid renal lesions and for characterizing complex renal cystic lesions and indeterminate renal masses [16-18]. CEUS may result in assignment of a higher Bosniak classification compared to contrast-enhanced CT [19,20]. However, a typical CEUS examination does not result in a complete evaluation of both kidneys for additional renal masses.


Indeterminate Renal Mass

Indeterminate Renal Mass. Tc-99m sestamibi single-photon emission computed tomography (SPECT)/CT has been shown in several studies to be helpful when the diagnosis of a renal oncocytoma is suspected [21-23]. For example, in a study of 31 renal masses imaged with Tc-99m sestamibi SPECT/CT, 91.6% (11 of 12) of oncocytomas had radiotracer uptake above aUniversity of California San Francisco School of Medicine, San Francisco, California. bPanel Chair, Northwestern University, Chicago, Illinois. cPanel Vice- Chair, UT Southwestern Medical Center, Dallas, Texas. dUniversity of Rochester Medical Center, Rochester, New York. eThe University of Texas MD Anderson Cancer Center, Houston, Texas. fUniversity of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; American Society of Nephrology. gUniversity of Washington, Seattle, Washington; American Urological Association. hDuke University Medical Center, Durham, North Carolina. iMayo Clinic, Rochester, Minnesota. jEmory University School of Medicine, Atlanta, Georgia. kThomas Jefferson University Hospital, Philadelphia, Pennsylvania. lCleveland Clinic, Cleveland, Ohio. mMedical University of South Carolina, Charleston, South Carolina; American Urological Association. nUniversity of Alabama at Birmingham, Birmingham, Alabama. oJohns Hopkins University School of Medicine, Washington, District of Columbia. pUniversity of Maryland School of Medicine, Baltimore, Maryland. qSpecialty Chair, University of Alabama at Birmingham, Birmingham, Alabama. Reprint requests to: publications@acr.org Indeterminate Renal Mass adjacent normal renal parenchyma, three hybrid tumors (mixed-type oncocytoma and chromophobe renal cancer) showed tracer uptake, one papillary RCC had a slight tracer uptake, and the remaining 11 RCC were sestamibi negative [23]. CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts.


Indeterminate Renal Mass

Indeterminate Renal Mass. There is variability in the specific parameters, but it usually involves unenhanced images followed by IV contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum intensity projection or 3-D volume rendering. For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast. CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the precontrast and excretory phases. MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phases. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract. OR Discussion of Procedures by Variant Variant 1: Indeterminate renal mass. No contraindication to either iodinated CT contrast or gadolinium- based MR intravenous contrast.


Indeterminate Renal Mass

Indeterminate Renal Mass. Initial imaging. Arteriography Kidney Cross-sectional imaging has replaced arteriography for the evaluation of indeterminate renal masses. There is no relevant literature regarding the use of arteriography in the evaluation of an indeterminate renal mass. Although CT with and without IV contrast is optimal for evaluation of indeterminate renal masses, CT without IV contrast can provide some information. For example, homogenous renal masses measuring <20 HU or >70 HU [1,2] or lesions containing macroscopic fat can be characterized as benign lesions on noncontrast CT. Other studies have also shown that dual-energy CT can differentiate between solid tumors and hyperdense cysts incidentally detected on a single-phase postcontrast CT [13-15] and can be useful when a comprehensive multiphase renal protocol CT is not available. Indeterminate Renal Mass Cystic Renal Masses The Bosniak CT classification system for cystic renal masses encompasses the spectrum from simple renal cyst to cystic RCC, with the likelihood of malignancy increasing with the complexity of the mass [28,29]. Because the presence of any enhancing nodules, walls, or thick septa within a cystic mass is key to determining the probability of malignancy using the Bosniak classification, CT without and with IV contrast is usually necessary for evaluating these lesions. One retrospective study of 156 Bosniak IIF lesions showed that 10.9% of the lesions progressed to malignancy between 6 months and 3.2 years [30]. Another retrospective study of 69 Bosniak IIF lesions and 144 Bosniak III lesions showed malignancy rates of 25% and 54%, respectively [31]. In one study of 312 prospectively classified Bosniak lesions, the malignancy rate at pathology was 38% for Bosniak IIF, 40% for Bosniak III, and 90% for Bosniak IV renal lesions [32]. Oncocytoma is another benign tumor that mimics RCC, and to date there are no specific CT features to reliably differentiate between the two [37].


Indeterminate Renal Mass

Indeterminate Renal Mass. Enhancement pattern on multiphasic CT has been used to subtype RCC. In a retrospective study of 298 cases of RCC and oncocytoma evaluated with 4-phase CT, multiphasic enhancement threshold helped to discriminate clear-cell RCC from oncocytoma with an accuracy of 77%, clear-cell RCC from papillary RCC with an accuracy of 85%, and clear-cell RCC from chromophobe RCC with an accuracy of 84% [38]. However, no prospective studies have validated the reported enhancement threshold, and accuracies of 77% to 85% may not be sufficient to change clinical management. CTU While there is no literature specifically evaluating the performance of CTU for indeterminate renal masses, CTU may be useful in this context. CTU that includes the acquisition of both unenhanced and nephrographic phase images would be expected to provide the same information as CT abdomen without and with IV contrast. The excretory phase images from CTU may provide additional information for differentiating between intrarenal urothelial carcinoma from centrally located RCC [39]. MRI Abdomen MRI is frequently used to characterize renal lesions. In one retrospective study of 120 patients, the specificity of MRI was significantly higher than that of CT in diagnosing RCC (68.1% versus 27.7%), whereas their sensitivities Indeterminate Renal Mass Ho et al [51] showed that the optimal percentage of enhancement threshold for distinguishing cysts from solid tumors on MRI was 15%. Hecht et al [52] reported that both quantitative and qualitative methods are sensitive in the detection of enhancement in a renal lesion on MRI and that subtracted images enable accurate assessment of tumor enhancement for intrinsically hyperintense lesions using qualitative methods. Although MRI without and with IV contrast is optimal for renal lesion characterization, MRI without IV contrast can also provide diagnostic information.


Indeterminate Renal Mass

Indeterminate Renal Mass. For example, simple cystic lesions, or even those with thin septations, can often be characterized on noncontrast T2-weighted imaging based on their homogeneous and very high T2 signal intensity. To differentiate between hemorrhagic or proteinaceous cyst and RCC, a retrospective study shows that homogenous high T1 signal intensity lesions with smooth borders and lesion to renal parenchyma signal intensity ratio of >1.6 predicted the lesion as a benign cyst [53]. Another study of 144 T1-hyperintense lesions demonstrated that diffuse and marked T1-hyperintensity achieved accuracies of 73.6% to 79.9% for the diagnosis of T1- hyperintense cysts [54]. An angular interface with the renal parenchyma on T2-weighted imaging has been shown to be 78% sensitive and 100% specific for differentiating benign exophytic renal masses from malignant masses [55]. Diffusion-weighted imaging, although less accurate than contrast-enhanced MRI, may have some ability to differentiate solid RCC from oncocytomas and characterize the histologic subtypes of RCC [56]. New and specialized MRI sequences have been proposed for the purposes of characterizing the vascularity of renal lesions in patients with renal dysfunction. For example, one small study of 17 renal lesions used arterial spin labeling to detect blood flow in renal masses, which correlated with malignancy [57]. Cystic Renal Masses In a study of 69 cystic renal masses evaluated using the Bosniak classification with CT and MRI, there was CT and MRI agreement in 56 of 69 lesions (81%) and disagreement in 13 of 69 lesions (19%) [29]. CT and MRI were felt to be similar in evaluation of most renal cystic mass lesions. However, MRI may depict additional findings, such as an increase in number of septa, septal or wall thickness, and enhancement. Such findings would result in MRI upgrading cystic lesions and thus might alter patient management [29].


Indeterminate Renal Mass

Indeterminate Renal Mass. Another study of 33 cystic lesions imaged with both 1.5T and 3.0T MRI showed that there is a greater tendency to upgrade cyst complexity and Bosniak cyst category at 3.0T than at 1.5T and thus suggested that serial follow-up of cystic renal lesions be performed at constant field strength [58]. Solid Renal Masses Other than AMLs with macroscopic fat, MRI cannot yet reliably differentiate benign from malignant renal tumors. However, several MRI features have been reported to be useful for suggesting types of solid renal tumors. In one multiparametric MRI study, lipid-poor AMLs were characterized by higher T1 signal intensity and lower T2 signal intensity compared to normal renal cortex and by greater arterial-to-delayed enhancement ratio than RCC [59]. Another study showed that the combination of low T2 signal and signal drop on chemical-shift imaging is specific for lipid-poor AMLs but lacks sensitivity, and the combination of low T2 signal intensity and high area under the contrast-enhanced MRI curve is sensitive and specific for lipid-poor AMLs [60]. Although both papillary RCC and lipid-poor AMLs can have low signal intensity on T2-weighted images, the presence of intratumoral hemorrhage seen on T1-weighted images was suggested to be a specific feature of papillary RCC [61]. Nonetheless, MRI findings of lipid-poor AMLs overlap with various RCC subtypes and remain difficult to prospectively diagnose [60]. Indeterminate Renal Mass diagnostic algorithm had diagnostic accuracy of 81% (88 of 109) and 91% (99 of 109) in the diagnosis of clear-cell RCC and papillary RCC, respectively, while achieving moderate to substantial inter-reader agreement among 7 radiologists [64]. MRU There is no relevant literature regarding the use of MRU in the evaluation of indeterminate renal masses. Radiography Intravenous Urography There is no relevant literature regarding the use of IV urography (IVU) in the evaluation of indeterminate renal masses.


Indeterminate Renal Mass

Indeterminate Renal Mass. US Abdomen with IV Contrast CEUS using microbubble agents is emerging as a useful way to characterize previously indeterminate renal lesions [16-18]. In a study of 1,018 indeterminate renal lesions, CEUS had a per patient sensitivity of 100% (126 of 126 patients), specificity of 95% (132 of 139 patients), positive predictive value of 94.7% (126 of 133 patients), and negative predictive value of 100% (132 of 132 patients) for classifying benign versus malignant renal masses [16]. In that study, any echogenic masses with enhancement equal to or greater than normal renal cortex and wash-out, and any masses with blood flow, were considered malignant. In another study, CEUS successfully classified 95.7% (90 of 94) previously indeterminate lesions and has an accuracy of 90.2% (37 of 41 lesions) when compared with the reference standard, including histopathology and follow-up [18]. In the subgroup analysis, CEUS was definitive for 94.4% (17 of 18) of cases referred because of equivocal enhancement at CT [18]. In that same study, CEUS was able to classify lesions in 100% (10 of 10) of the cases in which the lesions were indeterminate on prior MRI [18]. Another study of CEUS in 83 CT indeterminate renal masses reported that the accuracy of characterization by CEUS was 95.2% compared with 42.2% using unenhanced US [17]. Studies have shown CEUS to be more sensitive than contrast-enhanced CT in characterizing cystic renal masses [19,65]. In a study of 31 cystic renal masses evaluated by both CT and CEUS using the Bosniak classification, 26% of the lesions were upgraded by CEUS [19]. In a prospective CEUS study of 94 solid renal lesions excluding lipid- rich AML, hypovascularity of small solid renal masses relative to the cortex in the arterial phase has 100% specificity for detecting malignancy, especially for detecting papillary RCC [66]. Quantitative analysis of CEUS has also been reported to be useful to stratify RCC and benign renal tumors [67,68]. Variant 2: Indeterminate renal mass.


Indeterminate Renal Mass

Indeterminate Renal Mass. Contraindication to both iodinated CT and gadolinium-based MR intravenous contrast. Initial imaging. Arteriography Kidney Cross-sectional imaging has replaced arteriography for the evaluation of indeterminate renal masses. There is no relevant literature regarding the use of arteriography in the evaluation of indeterminate renal masses. Arteriography typically requires IV administration of iodinated contrast. CT Abdomen Iodinated CT contrast is contraindicated in some patients with severe allergy to the CT contrast or patients who are at high risk for contrast-induced nephropathy. For more details, please refer to the ACR Manual on Contrast Media [71]. The inability to utilize IV contrast to evaluate a renal mass markedly limits whether it can be classified as benign or malignant on CT, but it does provide some information if calcifications, nodules, or septations are visible. Homogenous renal masses measuring <20 HU or >70 HU [1,2] or lesions containing macroscopic fat can be characterized as benign lesions, but all other small lesions cannot be characterized using CT without IV contrast. Large lesions with calcifications and necrosis may not need further characterization, but detection of venous invasion and metastases is also limited. Indeterminate Renal Mass CTU There is no relevant literature regarding the use of CTU in the evaluation of indeterminate renal masses. MRI Abdomen Because of the risk for nephrogenic systemic fibrosis [72], certain gadolinium-based contrast agents may be contraindicated in patients with renal failure. Another contraindication is severe allergy to gadolinium agents. For more details, please refer to the ACR Manual on Contrast Media [71]. In the absence of contrast, unenhanced MRI has some advantages over unenhanced CT in the characterization of renal masses. Simple cystic lesions or even those with thin septations can often be characterized on noncontrast T2-weighted imaging based on their homogeneous and very high T2 signal intensity.


Indeterminate Renal Mass

Indeterminate Renal Mass. To differentiate between hemorrhagic or proteinaceous cysts and RCC, a retrospective study shows that homogenous high T1 signal intensity lesions with smooth borders and lesion to renal parenchyma signal intensity ratio of >1.6 predicted the lesion as a benign cyst [53]. Another study of 144 T1-hyperintense lesions demonstrated that diffuse and marked T1-hyperintensity achieved accuracies of 73.6% to 79.9% for the diagnosis of T1-hyperintense cysts [54]. An angular interface with the renal parenchyma on T2- weighted imaging has been shown to be 78% sensitive and 100% specific for differentiating benign exophytic renal masses from malignant masses [55]. Diffusion-weighted imaging, although less accurate than contrast-enhanced MRI, may have some ability to differentiate solid RCC from oncocytomas and characterize the histologic subtypes of RCC [56]. New and specialized MRI sequences have been proposed for the purposes of characterizing the vascularity of renal lesions in patients with renal dysfunction. For example, one small study of 17 renal lesions used arterial spin labeling to detect blood flow in renal masses, which correlated with malignancy [57]. A drawback of MRI compared with CT is the limited ability of MRI for detection of calcifications. MRU There is no relevant literature regarding the use of MRU in the evaluation of indeterminate renal masses. Radiography Intravenous Urography There is no relevant literature regarding the use of IVU for the evaluation of indeterminate renal masses. IVU requires IV administration of iodinated contrast. US Abdomen with IV Contrast CEUS using microbubble agents is emerging as a useful way to characterize previously indeterminate renal lesions [16-18]. It is not limited by renal or hepatic failure.


Indeterminate Renal Mass

Indeterminate Renal Mass. In one study of 1,018 indeterminate renal lesions, CEUS had a per patient sensitivity of 100% (126 of 126 patients), specificity of 95% (132 of 139 patients), positive predictive value of 94.7% (126 of 133 patients), and negative predictive value of 100% (132 of 132 patients) for classifying benign versus malignant renal masses [16]. In that study, any echogenic masses with enhancement at least of normal renal cortex and wash-out as well as any masses with blood flow were considered malignant. In another study, CEUS successfully classified 95.7% (90 of 94) of previously indeterminate lesions and has an accuracy of 90.2% (37 of 41 lesions) when compared with the reference standard, including histopathology and follow-up [18]. In the subgroup analysis, CEUS was definitive for 94.4% (17 of 18) of cases referred because of equivocal enhancement Indeterminate Renal Mass at CT [18]. In that same study, CEUS was able to classify lesions in 100% (10 of 10) of the cases in which the lesions were indeterminate on prior MRI [18]. Another study of CEUS in 83 CT indeterminate renal masses reported that the accuracy of characterization by CEUS was 95.2% compared with 42.2% using unenhanced US [17]. Studies have shown CEUS to be more sensitive than contrast-enhanced CT in characterizing cystic renal masses [19,65]. In a study of 31 cystic renal masses evaluated by both CT and CEUS using the Bosniak classification, 26% of the lesions were upgraded by CEUS [19]. In a prospective CEUS study of 94 solid renal lesions excluding lipid- rich AMLs, hypovascularity of small solid renal masses relative to the cortex in the arterial phase has 100% specificity for detecting malignancy, especially for detecting papillary RCC [66]. Quantitative analysis of CEUS has also been reported to be useful to stratify RCC and benign renal tumors [67,68]. Variant 3: Indeterminate renal mass. Contraindication only to iodinated CT intravenous contrast. Initial imaging.


Indeterminate Renal Mass

Indeterminate Renal Mass. Arteriography Kidney Cross-sectional imaging has replaced arteriography for the evaluation of indeterminate renal masses. There is no relevant literature regarding the use of arteriography in the evaluation of indeterminate renal masses. CT Abdomen Iodinated CT contrast is contraindicated in some patients with severe allergy to the CT contrast or in patients who are at high risk for contrast-induced nephropathy. For more details, please refer to the ACR Manual on Contrast Media [71]. The inability to utilize IV contrast to evaluate a renal mass markedly limits whether it can be classified as benign or malignant on CT, but it can provide some information. Homogenous renal masses measuring <20 HU or >70 HU [1,2] or lesions containing macroscopic fat can be characterized as benign lesions, but all other small lesions cannot be characterized using CT without IV contrast. Large lesions with calcifications and necrosis may not need further characterization, but detection of venous invasion and metastases is also limited. CTU There is no relevant literature regarding the use of CTU in the evaluation of indeterminate renal masses. Indeterminate Renal Mass Ho et al [51] showed that the optimal percentage of enhancement threshold for distinguishing cysts from solid tumors on MRI was 15%. Hecht et al [52] reported that both quantitative and qualitative methods are sensitive in the detection of enhancement in a renal lesion on MRI and that subtracted images enables accurate assessment of tumor enhancement for intrinsically hyperintense lesions using qualitative methods. Although MRI without and with IV contrast is optimal for renal lesion characterization, MRI without IV contrast can also provide diagnostic information. For example, simple cystic lesions or even those with thin septations can often be characterized on noncontrast T2-weighted imaging based on their homogeneous and very high T2 signal intensity.


Indeterminate Renal Mass

Indeterminate Renal Mass. To differentiate between hemorrhagic or proteinaceous cysts and RCC, a retrospective study shows that homogenous high T1 signal intensity lesions with smooth borders and lesion to renal parenchyma signal intensity ratio of >1.6 predicted the lesion as a benign cyst [53]. Another study of 144 T1-hyperintense lesions demonstrated that diffuse and marked T1 hyperintensity achieved accuracies of 73.6% to 79.9% for the diagnosis of T1- hyperintense cysts [54]. An angular interface with the renal parenchyma on T2-weighted imaging has been shown to be 78% sensitive and 100% specific for differentiating benign exophytic renal masses from malignant masses [55]. Diffusion-weighted imaging, although less accurate than contrast-enhanced MRI, may have some ability to differentiate solid RCC from oncocytomas and characterize the histologic subtypes of RCC [56]. New and specialized MRI sequences have been proposed for the purposes of characterizing the vascularity of renal lesions in patients with renal dysfunction. For example, one small study of 17 renal lesions used arterial spin labeling to detect blood flow in renal masses, which correlated with malignancy [57]. Cystic Renal Masses In a patient who cannot receive iodinated contrast, MRI without and with IV contrast is a good alternative. MRI may depict findings like an increase in number of septa, septal or wall thickness, and enhancement; these may result in MRI upgrading cystic lesions and thus might alter patient management [29]. Another study of 33 cystic lesions imaged with both 1.5T and 3.0T MRI showed that there is a greater tendency to upgrade cyst complexity and Bosniak cyst category at 3.0T than at 1.5T and thus suggested that serial follow-up of cystic renal lesions be performed at constant field strength [58]. MRU There is no relevant literature regarding the use of MRU in the evaluation of indeterminate renal masses. Indeterminate Renal Mass


Indeterminate Renal Mass

Indeterminate Renal Mass. Radiography Intravenous Urography There is no relevant literature regarding the use of IVU for the evaluation of indeterminate renal masses. US Abdomen with IV Contrast CEUS using microbubble agents is emerging as a useful way to characterize previously indeterminate renal lesions [16-18]. In one study of 1,018 indeterminate renal lesions, CEUS had a per patient sensitivity of 100% (126 of 126 patients), specificity of 95% (132 of 139 patients), positive predictive value of 94.7% (126 of 133 patients), and negative predictive value of 100% (132 of 132 patients) for classifying benign versus malignant renal masses [16]. In that study, any echogenic masses with enhancement at least of normal renal cortex and wash-out, as well as any masses with blood flow, were considered malignant. In another study, CEUS successfully classified 95.7% (90 of 94) previously indeterminate lesions, and had an accuracy of 90.2% (37 of 41 lesions) when compared with the reference standard, including histopathology and follow-up [18]. In the subgroup analysis, CEUS was definitive for 94.4% (17 of 18) of cases referred because of equivocal enhancement at CT [18]. In that same study, CEUS was able to classify lesions in 100% (10 of 10) of the cases in which the lesions were indeterminate on prior MRI [18]. Another study of CEUS in 83 CT indeterminate renal masses reported that the accuracy of characterization by CEUS was 95.2% compared with 42.2% using unenhanced US [17]. In a prospective CEUS study of 94 solid renal lesions, excluding lipid-rich AML, hypovascularity of small solid renal masses relative to the cortex in the arterial phase has 100% specificity for detecting malignancy, especially for detecting papillary RCC [66]. Quantitative analysis of CEUS has also been reported to be useful to stratify RCC and benign renal tumors [67,68]. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain.  OR aUniversity of Missouri Health Care, Columbia, Missouri. bPanel Chair, Mayo Clinic Arizona, Phoenix, Arizona. cPanel Vice-Chair, University of Virginia Health System, Charlottesville, Virginia. dUniversity of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. eMayo Clinic, Rochester, Minnesota. fHospital for Special Surgery, New York, New York. gThe Centers for Advanced Orthopaedics, George Washington University, Washington, DC and Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; American Academy of Orthopaedic Surgeons. hDuke University Medical Center, Durham, North Carolina. iUniversity of Missouri School of Medicine, Columbia, Missouri, Primary care physician. jCleveland Clinic, Cleveland, Ohio. kPenn State Milton S. Hershey Medical Center, Hershey, Pennsylvania and Uniformed Services University of the Health Sciences, Bethesda, Maryland. lThe Ohio State University Wexner Medical Center, Columbus, Ohio; Commission on Nuclear Medicine and Molecular Imaging. mSpecialty Chair, VA San Diego Healthcare System, San Diego, California. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Chronic Hand and Wrist Pain Discussion of Procedures by Variant Variant 1: Adult. Chronic hand or wrist pain. Initial imaging. Bone Scan Area of Interest There is no relevant literature to support the use of bone scan as the first imaging study in the evaluation of chronic hand or wrist pain. CT Area of Interest With IV Contrast There is no relevant literature to support the use of CT with IV contrast as the first imaging study in the evaluation of chronic hand or wrist pain.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT without and with IV contrast as the first imaging study in the evaluation of chronic hand or wrist pain. CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT without IV contrast as the first imaging study in the evaluation of chronic hand or wrist pain. CT Arthrography Area of Interest There is no relevant literature to support the use of CT arthrography as the first imaging study in the evaluation of chronic hand or wrist pain. MR Arthrography Area of Interest There is no relevant literature to support the use of MR arthrography as the first imaging study in the evaluation of chronic hand or wrist pain. MRI Area of Interest Without and With IV Contrast There is no relevant literature to support the use of MRI without and with IV contrast as the first imaging study in the evaluation of chronic hand or wrist pain. MRI Area of Interest Without IV Contrast There is no relevant literature to support the use of MRI without IV contrast as the first imaging study in the evaluation of chronic hand or wrist pain. Radiographic Arthrography Area of Interest There is no relevant literature to support the use of radiographic arthrography contrast as the first imaging study in the evaluation of chronic hand or wrist pain. Radiography Area of Interest The imaging evaluation of chronic hand or wrist pain should begin with radiographs [6-12]. In many cases, radiographs may be the only imaging examination needed to establish a diagnosis or confirm a clinically expected diagnosis. The standard radiographic evaluation of both the hand and wrist includes 3 views: posteroanterior, lateral, and oblique [9]. The standard projections allow assessment of alignment including ulnar variance, joint spaces, impaction syndromes, static instability, chronic healed and nonunited fractures, soft tissue mineralization, erosions, and soft tissue swelling.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. US Area of Interest Given the superficial location of the joints, ligaments, muscles, tendons, and nerves of the hand and wrists, US is a useful tool in the assessment of chronic hand and wrist pain bolstered by the ability to readily perform and dynamic examination and evaluate the contralateral side [9,13]. US is optimally performed using high-frequency (10-15 MHz) linear transducers [11,13]. US can be used to identify synovitis, joint effusion, tenosynovitis, tendinopathy and tendon injury, pulley injury, carpal tunnel syndrome (CTS), and retained foreign body [6,13-16]. The American College of Rheumatology has concluded there is reasonable evidence to support the use of musculoskeletal US in patients without definitive diagnosis presenting with pain, swelling, or mechanical symptoms of the wrist, metacarpophalangeal, and interphalangeal joints; US is reasonable to evaluate tendon and soft tissue pathology of the hand and wrist and to assess for entrapment of the median or ulnar nerves [14]. In a study of patients referred from hand surgeons, US of the hand and wrist was contributory to the clinical assessment, defined as confirming the clinical suspicion or modifying the diagnostic/therapeutic plan in 76% of all patients and 67% of patient who presented without a history Chronic Hand and Wrist Pain of trauma [17]. Although there are many advantages to US evaluation for chronic hand and wrist pain, an interdisciplinary group of hand surgeons and radiologists recommended against the inclusion of US in the standard evaluation of scapholunate instability [18]. Variant 2: Adult. Chronic wrist pain. Radiographs normal or remarkable for nonspecific arthritis. Next imaging study. This variant is a guide on appropriate imaging use early in the assessment of chronic wrist pain, when standard radiographic projections are normal or show nonspecific arthritis.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. For purposes of this variant, a nonspecific arthritis is defined as articular changes at a single joint and/or a pattern of arthritis throughout the hand and wrist that, when combined with the appropriate clinical history, does not allow distinction between degenerative or post-traumatic osteoarthritis, inflammatory arthritis, and crystalline arthritis. Bone Scan Wrist There is no relevant literature discussing routine use of bone scan in the assessment of nonspecific chronic wrist pain. Bone scans offer the ability to differentiate metabolically active abnormalities, which may be the cause of pain, from those that are inactive [19]. Bone scans can reliably detect chronic or occult scaphoid fracture with a sensitivity and specificity of 97% and 89%, respectively [20]. Although bone scans are sensitive for the detection of bone abnormalities, the findings may be nonspecific [19]. There are established imaging patterns for fracture, osteonecrosis, nonunited fracture, arthritis, and complex regional pain syndrome [19]. Bone scan of the wrist offers improved specificity when single-photon emission CT is performed [19]. CT Arthrography Wrist Performing arthrography before a CT scan of the wrist aids in the detection of ligament injuries and cartilage abnormalities. CT arthrography allows direct visualization of full thickness ligament tears and visualization of partial thickness tears of the appropriate compartment [6,21]. An interdisciplinary group of hand surgeons and radiologists supports the use of CT arthrography for the assessment of clinically suspected scapholunate instability and cartilage defects [18]. CT arthrography has demonstrated a sensitivity, specificity, and accuracy between 92% and 94% for triangular fibrocartilage (TFC) complex tears, between 80% and 100% for intrinsic ligament tears located within the proximal carpal compartment, and between 94% and 100% for articular cartilage abnormalities [22].


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. In a study assessing the diagnostic performance of CT arthrography in cadavers, CT arthrography was more sensitive for the diagnosis of scapholunate and lunotriquetral tears when compared with MRI at 1.5T and performed particularly well in assessment of the dorsal segment of the scapholunate ligament [23]. CT Wrist With IV Contrast There is no relevant literature to support the use of CT wrist with IV contrast in the setting of chronic wrist pain and normal radiographs or radiographs remarkable for nonspecific arthritis. CT Wrist Without and With IV Contrast There is no relevant literature to support the use of CT wrist without and with IV contrast in the setting of chronic wrist pain and normal radiographs or radiographs remarkable for nonspecific arthritis. CT Wrist Without IV Contrast CT of the wrist provides a detailed assessment of the cortical and trabecular bone with a high spatial resolution. CT is the ideal modality to assess fracture healing, malunion, and articular surface incongruity [6,24]. CT is particularly useful in assessment of the DRUJ. When there is clinical concern for DRUJ instability, CT can be used to image the symptomatic and contralateral wrist simultaneously in the neutral, supinated, and pronated positions to assess for instability [24-26]. CT without IV contrast has been shown to be beneficial in operative planning for scaphoid fracture [27,28]. A disadvantage of CT compared with both MRI and US is its decreased contrast resolution and lower sensitivity in the detection of soft tissue abnormalities. MR Arthrography Wrist Direct MR arthrography is performed following the intra-articular injection of gadolinium and improves the detection and interobserver agreement for abnormalities of the wrist. MR arthrography is a minimally invasive imaging examination that may be appropriate for cases of suspected intrinsic ligament injury, TFC complex injury, cartilage abnormality, or surgical planning.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. Injection of any combination of the 3 compartments (DRUJ, radiocarpal, midcarpal) can be performed depending on the clinical question [13]. If the injection is performed with fluoroscopy, Chronic Hand and Wrist Pain comparison of the MR images with the fluoroscopic images is an essential step in image interpretation [13]. In most cases, a radiocarpal injection is performed; however, if there is concern for an ulnar sided detachment of the TFC, an additional DRUJ injection should be considered [7]. With single, radiocarpal injection, the sensitivity for TFC tears, intrinsic ligament injury, and cartilage lesions of the radiocarpal joint ranged from 63% to 100%, with specificity ranging from 89% to 97% [29]. MRI Wrist Without and With IV Contrast There is no relevant literature discussing the routine use of MRI wrist without and with IV contrast for the evaluation of chronic wrist pain and normal or nonspecific radiographs. The addition of postcontrast imaging to wrist MRI aids in distinguishing synovitis from joint effusion and ganglion cysts [9,35]. Similarly, postcontrast MRI aids in the detection of tenosynovitis [35]. For these reasons, MRI without and with IV contrast is usually appropriate in the evaluation of chronic joint pain with clinical suspicion of rheumatoid arthritis or seronegative spondyloarthropathy [2] and in cases of suspected septic arthritis or soft tissue infection [3]. MRI Wrist Without IV Contrast MRI without IV contrast is useful in the assessment of wrist pain. MRI is useful in assessing abnormalities of the bones, including bone marrow, and soft tissues, including the ligaments, TFC, tendons, and nerves. When using arthroscopy as the reference standard, the sensitivity and specificity of 3.0T MRI in the evaluation of scapholunate tear range from 70% to 87% and 90% to 97%, respectively, for lunotriquetral tear range from 50% to 63% and 94% to 97% respectively, and for TFC tear range from 63% to 100% and 42% to 100%, respectively [32,36-40].


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. A study of 18 patients demonstrated good correlation between cartilage lesions at 3.0T MRI and arthroscopy [37]. If a study is specifically performed to assess the intrinsic ligaments or TFC, MR arthrography has been demonstrated to be superior to MRI without IV contrast [30-32,41]. MRI is helpful in the diagnosis of tendon abnormalities including tendinopathy, tenosynovitis, and intersection syndromes [12,13,42,43]. In a retrospective review of 316 consecutive patients referred to a hand surgeon with MRI of the hand or wrist, MRI changed clinical management in 69.5% of cases [44]. MRI was particularly useful in reassuring patients that no further follow-up was necessary in 70% of cases [44]. Radiographic Arthrography Wrist There is no relevant literature to support the use of radiographic arthrography of the wrist in the setting of chronic wrist pain and normal or nonspecific radiographs. Although a meta-analysis has demonstrated a pooled sensitivity of 76.2% and a specificity of 92.5% for the detection of complete TFC complex tear, radiographic arthrography is not routinely performed in isolation [45]. In current practice it is infrequently performed as a standalone imaging examination; rather, it is typically performed in conjunction with CT or MR arthrography. Radiography Wrist Additional Views A variety of additional radiographic projections of the wrist may be obtained to supplement the standard 3-view series depending on the specific clinical indication. However, there is no recent literature to support obtaining additional views in the setting of chronic wrist pain and normal or nonspecific radiographs. An interdisciplinary group of hand surgeons and radiologists consensus statements concluded stress views are indicated for the diagnosis of scapholunate instability [18].


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. US Wrist US can be used to identify synovitis, joint effusion, tenosynovitis, tendinopathy and tendon injury, CTS, metacarpophalangeal joint collateral ligament injury, extensor hood injury, and retained foreign body [6,13,14,16,46]. The American College of Rheumatology has concluded there is reasonable evidence to support the use of musculoskeletal US in patients without definitive diagnosis presenting with pain, swelling, or mechanical symptoms of the wrist; US is reasonable to evaluate tendon and soft tissue pathology of the wrist and to assess for entrapment of the median or ulnar nerves [14]. In a study of patients referred from hand surgeons, US of the hand and wrist was contributory to the clinical assessment, defined as confirming the clinical suspicion or modifying the diagnostic/therapeutic plan, in 76% of all patients and 67% of patients who presented without a history of trauma Chronic Hand and Wrist Pain [17]. Although there are many advantages to US evaluation for chronic hand and wrist pain, an interdisciplinary group of hand surgeons and radiologists recommended against the inclusion of US in the standard evaluation of scapholunate instability [18]. Variant 3: Adult. Chronic hand pain. Radiographs normal or remarkable for nonspecific arthritis. Next imaging study. Bone Scan Hand There is no relevant literature to support the use of bone scan in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis. CT Arthrography Hand There is no relevant literature to support the use of CT arthrography in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis. CT Hand With IV Contrast There is no relevant literature to support the use of CT hand with IV contrast in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. CT Hand Without and With IV Contrast There is no relevant literature to support the use of CT hand with IV contrast in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis. CT Hand Without IV Contrast There is no relevant literature to support the use of CT hand without IV contrast in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis. MR Arthrography Hand There is no relevant literature to support the use of MR arthrography in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis. MRI Hand Without and With IV Contrast There is no relevant literature discussing routine use of MRI hand without and with IV contrast in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis. In the research setting, contrast-enhanced MRI can identify synovitis, periarticular bone marrow edema, and tenosynovitis, which correlates with patient pain in the setting of hand osteoarthritis [47,48]. MRI Hand Without IV Contrast MRI hand without IV contrast is of limited benefit in the setting of nonspecific pain. A study evaluating hand MRI in the setting of erosive osteoarthritis showed no difference in the assessment of joint space narrowing, bone erosion, and malalignment compared with radiographs [49]. MRI can demonstrate many abnormalities that result in chronic pain including arthritis, carpal boss, tendinopathy, tenosynovitis, pulley injury, extensor hood injury, sagittal band injury, volar plate injury, chondral injury, and ligament injury [13,50-54]. In a retrospective review of 316 consecutive patients referred to a hand surgeon with MRI of the hand or wrist, MRI changed clinical management in 69.5% of cases [44]. MRI was particularly useful in reassuring patients that no further follow-up was necessary in 70% of cases [44].


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. Radiographic Arthrography Hand There is no relevant literature to support the use of radiographic arthrography in the setting of chronic hand pain and normal radiographs or radiographs remarkable for nonspecific arthritis. US Hand US can be used to identify synovitis, joint effusion, tenosynovitis, tendinopathy and tendon injury, pulley injury, CTS, and retained foreign body [6,13-16]. The American College of Rheumatology has concluded there is reasonable evidence to support the use of musculoskeletal US in patients without definitive diagnosis presenting with pain, swelling, or mechanical symptoms of the metacarpophalangeal and interphalangeal joints, and US is reasonable to evaluate tendon and soft tissue pathology of the hand [14]. In a study of patients referred from hand surgeons, US of the hand and wrist was contributory to the clinical assessment, defined as confirming the clinical suspicion or modifying the diagnostic/therapeutic plan, in 76% of all patients and 67% of patient who presented without a history of trauma [17]. Chronic Hand and Wrist Pain Variant 4: Adult. Chronic wrist pain. Radiographs show old scaphoid fracture. Evaluate for nonunion, malunion, osteonecrosis, or post-traumatic osteoarthritis. Next imaging study. Bone Scan Wrist There is no relevant literature to support the use of bone scan in the setting of chronic wrist pain, remote scaphoid fracture, and clinical concern for nonunion, malunion, osteonecrosis, or post-traumatic osteoarthritis. CT Arthrography Wrist There is no relevant literature to support the use of CT arthrography in the setting of chronic wrist pain, remote scaphoid fracture, and clinical concern for nonunion, malunion, or osteonecrosis. If the specific clinical concern requires assessment of the articular cartilage in post-traumatic osteoarthritis, the spatial resolution of CT when combined with intra-articular contrast makes CT arthrography an ideal study.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. CT arthrography has demonstrated a sensitivity, specificity, and accuracy between 94% and 100% for articular cartilage injury [22]. CT Wrist With IV Contrast CT wrist with IV contrast is not routinely performed in clinical practice, although there is an isolated report of dual- energy CT with IV contrast used to assess scaphoid osteonecrosis. In addition to the benefits afforded by the high spatial resolution of CT in the assessment of scaphoid fracture, the addition of contrast has been shown to be beneficial in the determination of proximal pole viability. A study of 19 wrists in 18 patients with dual-energy contrast-enhanced CT showed promising results in the assessment of proximal pole osteonecrosis in the setting of scaphoid fracture [55]. When compared with intraoperative assessment or histologic analysis, in a series of 18 patients who underwent dual-energy contrast-enhanced CT of the wrist there was a sensitivity of 100% and a specificity of 94% for the assessment of osteonecrosis of the proximal pole of the scaphoid following fracture [55]. CT Wrist Without and With IV Contrast There is no relevant literature to support the use of CT with IV contrast in the setting of chronic wrist pain, remote scaphoid fracture, and clinical concern for nonunion, malunion, osteonecrosis, or post-traumatic osteoarthritis. CT Wrist Without IV Contrast The spatial resolution obtained with CT makes it well suited to assess for any trabecular bridging at the fracture site, nonunion, malunion, and the sclerosis and fragmentation of avascular necrosis. The isotropic acquisition and the ability to create 3-D models assists in surgical planning [27,28]. MR Arthrography Wrist There is no relevant literature to support the use of MR arthrography in the setting of chronic wrist pain, remote scaphoid fracture, and clinical concern for nonunion, malunion, or osteonecrosis.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. If the specific clinical concern requires assessment of the articular cartilage in post-traumatic osteoarthritis, the addition of arthrography to MRI improves the assessment of the articular cartilage [31]. However, CT arthrography has a higher sensitivity and specificity for articular cartilage defect compared with MR arthrography [31,56]. MRI Wrist Without and With IV Contrast MRI wrist without and with IV contrast can demonstrate both nonunited and malunited scaphoid fractures. Although 3.0T MRI without IV contrast falls behind MR and CT arthrography in the assessment of the articular cartilage, it has demonstrated a modest sensitivity of 48% to 52% and a good specificity of 82% compared with visual inspection in a cadaver study [57]. The added benefit of MRI comes in the assessment for osteonecrosis in the proximal pole scaphoid following scaphoid fracture. Whether contrast-enhanced MRI is superior to noncontrast MRI for assessment of scaphoid osteonecrosis is controversial. In a study comparing the addition of postcontrast images with the unenhanced MRI in 30 patients, the addition of contrast increased the sensitivity (66% versus 36%), specificity (88% versus 78%), and accuracy (83% versus 68%) when compared with the noncontrast images alone [58]. MRI Wrist Without IV Contrast MRI wrist without IV contrast can demonstrate both nonunited and malunited scaphoid fractures. Although 3.0T MRI without IV contrast falls behind MR and CT arthrography in the assessment of the articular cartilage, it has demonstrated a modest sensitivity of 48% to 52% and a good specificity of 82% compared with visual inspection in a cadaver study [57]. The added benefit of MRI comes in the assessment for osteonecrosis in the proximal pole scaphoid following scaphoid fracture. Whether contrast-enhanced MRI is superior to noncontrast MRI for assessment of scaphoid osteonecrosis is controversial. A study of noncontrast MRI in 29 patients with scaphoid Chronic Hand and Wrist Pain


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. nonunion demonstrated a sensitivity of 55%, a specificity of 94%, and an accuracy of 79% for the diagnosis of osteonecrosis compared with intraoperative assessment [59]. Radiographic Arthrography Wrist There is no relevant literature to support the use of radiographic arthrography in the setting of chronic wrist pain, remote scaphoid fracture, and clinical concern for nonunion, malunion, osteonecrosis, or post-traumatic osteoarthritis. US Wrist There is no relevant literature to support the use of US in the setting of chronic wrist pain, remote scaphoid fracture, and clinical concern for nonunion, malunion, osteonecrosis, or post-traumatic osteoarthritis. Variant 5: Adult. Chronic hand or wrist pain. Radiographs normal or indeterminate. Symptoms suspicious for carpal tunnel syndrome. Next imaging study. Bone Scan Area of Interest There is no relevant literature to support the use of bone scan in the setting of chronic hand and wrist pain with clinical concern for CTS. CT Area of Interest With IV Contrast There is no relevant literature to support the use of CT with IV contrast in the setting of chronic hand and wrist pain with clinical concern for CTS. CT Area of Interest Without and With IV Contrast There is no relevant literature to support the use of CT without and with IV contrast in the setting of chronic hand and wrist pain with clinical concern for CTS. CT Area of Interest Without IV Contrast There is no relevant literature to support the use of CT without IV contrast in the setting of chronic hand and wrist pain with clinical concern for CTS. CT Arthrography Area of Interest There is no relevant literature to support the use of CT arthrography in the setting of chronic hand and wrist pain with clinical concern for CTS. MR Arthrography Area of Interest There is no relevant literature to support the use of MR arthrography in the setting of chronic hand and wrist pain with clinical concern for CTS.


Chronic Hand and Wrist Pain

Chronic Hand and Wrist Pain. MRI Area of Interest Without and With IV Contrast There is no relevant literature to support the use of MR without and with IV contrast in the setting of chronic hand and wrist pain with clinical concern for CTS. MRI Area of Interest Without IV Contrast MRI can identify enlargement and flattening of the median nerve, bowing of the flexor retinaculum, space occupying lesions, anatomic variants including bifid median nerve and persistent median artery, and tendon pathology in the carpal tunnel [60-62]. When compared with clinical assessment and nerve conduction studies, MRI can diagnose CTS with a high accuracy and stage severity with moderate accuracy [62,63]. There is good correlation between the cross-sectional area of the median nerve as assessed by both US and MRI [63,64]. However, MRI of the wrist is typically not indicated in the setting of suspected CTS [60-62]. Radiographic Arthrography Area of Interest There is no relevant literature to support the use of radiographic arthrography in the setting of chronic hand and wrist pain with clinical concern for CTS. Radiography Wrist Additional Views There is no relevant literature to support the use of additional radiographic views in the setting of chronic hand and wrist pain with clinical concern for CTS. US Area of Interest When compared with clinical assessment and electrophysiologic studies, multiple systematic reviews and meta- analyses have demonstrated US to be highly sensitive and specific for the diagnosis of CTS [65-69]. The measurements and calculations used in the literature for US evaluation of the median nerve are heterogeneous; Chronic Hand and Wrist Pain cross-sectional area measurements of the median nerve at multiple locations in the forearm and wrist and ratios or differences in cross-sectional area comparing the various measurements have been reported.