Imaging of Mesenteric Ischemia

Imaging of Mesenteric Ischemia. Chronic mesenteric ischemia occurs because of occlusive or stenotic atherosclerotic disease and most commonly involves at least 2 or 3 main vessels. It is more prevalent in the elderly population and in patients with major risk factors for atherosclerosis, such as hypertension, hyperlipidemia, and smoking history [12]. Discussion of Procedures by Variant Variant 1: Suspected acute mesenteric ischemia. Initial Imaging. Patients with acute mesenteric ischemia present with abdominal pain out of proportion to the physical examination [2]. A high index of suspicion is necessary to achieve early diagnosis, particularly in the elderly or hospitalized patient population [13,14]. The main challenge is to differentiate acute mesenteric ischemia from Reprint requests to: publications@acr.org Imaging of Mesenteric Ischemia other more common causes of acute abdominal pain, such as appendicitis, diverticulitis, peptic ulcer disease, acute pancreatitis, gastroenterocolitis, nephrolithiasis, cholelithiasis, and cholecystitis. Early in the course of disease, laboratory findings are of little value in differentiating among these causes, with the results usually demonstrating metabolic acidosis, elevated lactate and D-dimer, leukocytosis, hemoconcentration, elevated amylase levels, and/or abnormal liver enzymes [15,16]. Unfortunately, the signs, symptoms, and laboratory testing are insufficient for making the diagnosis [15]. Radiography Abdomen Radiography has historically been considered the first imaging modality in the evaluation of acute abdominal pain, but because of its low diagnostic yield and generally nonspecific findings, its role has been debated in current practice [17]. Abdominal radiography does not exclude the diagnosis of acute mesenteric ischemia as 25% of patients with this condition will have normal radiographs [18].


Imaging of Mesenteric Ischemia

Imaging of Mesenteric Ischemia. Radiography findings in patients with acute mesenteric ischemia are usually nonspecific, late, and associated with a high mortality rate, as they often first appear when bowel infarction has already occurred [5,18-20]. A radiograph typically shows bowel dilatation in elderly patients and a gasless abdomen in younger patients with acute mesenteric ischemia [21]. Hepatic portal venous gas is a rare but important radiographic finding associated with several pathological processes, including bowel necrosis secondary to acute mesenteric ischemia. Portal venous gas can occur alone or in association with pneumatosis intestinalis. When associated with pneumatosis intestinalis, it usually indicates the presence of advanced mesenteric ischemia [18]. In addition, given its limited role in assessing for other causes of acute abdominal pain, radiographs in mesenteric ischemia should be solely utilized to screen for bowel perforation or obstruction [17]. All elements are essential: 1) timing, 2) reconstructions/reformats, and 3) 3-D renderings. Standard CTs with contrast also include timing issues and recons/reformats. Only in CTA, however, is 3-D rendering a required element. This corresponds to the definitions that the CMS has applied to the Current Procedural Terminology codes. CTA of the abdomen and pelvis is a fast, accurate, and noninvasive diagnostic tool for evaluating the bowel and assessing intestinal vasculature and should be the first-step imaging approach in patients with acute bowel ischemia [12,15,23-28]. CTA can be helpful in stratifying patients to identify those who would benefit from angiography as opposed to the ones who should undergo emergent surgery. Grading the degree of arterial stenosis with CTA has also been shown to be highly accurate compared to digital subtraction imaging (DSA) as well as other imaging modalities, including US and MRA [29].


Imaging of Mesenteric Ischemia

Imaging of Mesenteric Ischemia. A negative or neutral oral contrast, such as low-density barium sulfate or water, has been advocated to distend the small bowel and better evaluate the bowel wall for thickening and enhancement; however this may not be possible in the acute setting [30]. Both arterial and portal venous phases should be included as part of the protocol to assess both arterial and venous patency [25,30,31]. Three-dimensional (3-D) rendering may also assist in evaluating the vasculature and should be performed [24,32]. A noncontrast phase is typically obtained as part of the CTA and may be helpful in identifying intramural hemorrhage, atherosclerotic calcifications, and to serve as baseline for assessing wall enhancement; however, several studies have shown that obtaining the noncontrast phase may not be required for accurate acute ischemia diagnosis [25,31,33-35]. CT imaging of the abdomen and pelvis also allows accurate evaluation of the entire gastrointestinal and genitourinary tract, helping to exclude most of the other causes of acute and chronic abdominal pain, including cholelithiasis, cholecystitis, pancreatitis, appendicitis, diverticulosis with or without diverticulitis, and nephrolithiasis. Vascular CT findings include arterial stenosis, embolism, thrombosis, arterial dissection, and mesenteric vein thrombosis. Nonvascular CT findings include bowel-wall thickening, hypoperfusion and hypoattenuation, bowel dilatation, bowel-wall hemorrhage, mesenteric fat stranding, pneumatosis intestinalis, and portal venous gas. Quantitative methods of assessing bowel enhancement may also add value in identifying ischemic bowel [36]. Imaging of Mesenteric Ischemia CTA is also preferred in patients with renal insufficiency with GFR under 30 who have suspected acute ischemia as benefits of a fast and accurate diagnosis will generally outweigh risks associated with potential risk of contrast- induced nephropathy [37,38].


Imaging of Mesenteric Ischemia

Imaging of Mesenteric Ischemia. Overall, CTA is an accurate technique for acute mesenteric ischemia diagnosis, with reported sensitivity and specificity as high as 93% to 100% and potential to improve patient survival [1,12,15,25,35,39-41]. CT Abdomen and Pelvis CT of the abdomen and pelvis with intravenous (IV) contrast performed during the venous phase has been less well studied compared with CTA in diagnosing mesenteric ischemia. CT with IV contrast can assess nonvascular findings, major arterial lesions, and mesenteric veins; however, the lack of arterial phase may lead to suboptimal evaluation of the mesenteric arteries compared to CTA [25,42]. Schieda et al [42] showed that CT during portal venous phase identified major arterial lesions, although several diagnostic errors occurred when relying on this phase only. Arterial phase influenced care in 19% of patients compared to portal venous phase alone in one study [25]. Because CT with IV contrast is typically performed with oral contrast as well, this additional step may potentially lead to delay in image acquisition and diagnosis. Therefore, CTA is preferred over CT with IV contrast during venous phase as the initial examination when mesenteric ischemia is suspected. There is a lack of relevant literature regarding the use of CT without IV contrast in the evaluation of acute mesenteric ischemia. Nonvascular findings, such as bowel dilation, wall thickening, mesenteric fluid, pneumatosis, and portomesenteric gas, can be identified with a noncontrast CT; however, these tend to be nonspecific or found in more advanced ischemia with a worse prognosis [40,42]. Blachar et al [43] showed that there was worse performance for CT without IV contrast compared to CT with IV contrast, although this was not statistically significant. However, in the same study, the most significant signs of ischemia, arterial filling defects, and decreased bowel wall enhancement, relied on IV contrast, emphasizing the use of contrast when possible [25,31,43].


Imaging of Mesenteric Ischemia

Imaging of Mesenteric Ischemia. Similarly to CT with IV contrast, oral contrast administration may delay the examination if it is routinely performed. CT without and with IV contrast is not indicated in the evaluation of suspected acute mesenteric ischemia. MRA Abdomen and Pelvis Magnetic resonance angiography (MRA) of the abdomen and pelvis with IV contrast has high sensitivity and specificity for diagnosing severe stenosis or occlusion at the origins of the celiac axis and SMA [44-47]. However, it has a limited role in diagnosing distal stenosis as well as nonocclusive mesenteric ischemia, and its use may delay therapeutic options in acute settings because it is a long examination. MRA is tailored to depict mesenteric vasculature and less likely to show ischemic findings within the bowel itself compared to CT, such as pneumatosis and portovenous gas; it is also unlikely to provide additional information in the acute setting if portal venous phase CT has already been performed [48]. MRA without contrast can be attempted in some cases; however, evaluation of smaller vessels may be suboptimal [46]. In the past decade with the advances in technology, CTA supplanted conventional angiography as the first-line imaging technique for acute mesenteric ischemia, and angiography transitioned to complementary diagnostic role with an option of endovascular treatment for revascularization candidates [57-62]. Although there is a lack of Level I evidence demonstrating clear benefits of endovascular therapy compared to open surgery in patients with acute mesenteric ischemia, the available data from systematic reviews and case series show that the endovascular approach is becoming more common and is associated with decreased mortality and need for laparotomy [57-62]. Nonetheless, acute mesenteric ischemia is a vascular surgical emergency requiring immediate surgical evaluation and angiography should not be considered in patients with significant hypovolemia or hypotension.


Imaging of Mesenteric Ischemia

Imaging of Mesenteric Ischemia. Urgent bowel reperfusion with the goal of infarction prevention is paramount and requires early diagnosis and involvement of Imaging of Mesenteric Ischemia vascular surgery, interventional radiology, and intensive care unit who need to work collaboratively, guiding resuscitation efforts and future treatment. US Duplex Doppler Abdomen The efficacy of ultrasound (US) in diagnosing acute mesenteric ischemia has been evaluated in many studies. US can demonstrate proximal mesenteric vessel thrombosis via Doppler mode and can be used in detecting proximal superior mesenteric and celiac artery stenosis with high sensitivity and specificity of 85% to 90% [63,64]. US may also reveal focal superior mesenteric or portal venous thrombosis in cases of venous occlusive ischemia [65]. Unfortunately, the presence of overlying bowel gas, obesity, and vascular calcifications are challenges for an adequate sonographic evaluation. In addition, duplex US has a limited role in detecting distal arterial emboli or in diagnosing nonocclusive mesenteric ischemia. Moreover, the length of the examination and the possible pain associated with the applied pressure to the abdomen during imaging may be limiting factors in initial evaluation of patients with suspected acute mesenteric ischemia [12,63,66]. Variant 2: Suspected chronic mesenteric ischemia. Initial Imaging. In the setting of chronic mesenteric ischemia, patients classically present with the clinical triad of postprandial abdominal pain 30 to 60 minutes after food consumption, weight loss, and food avoidance. Nausea and vomiting, postprandial diarrhea, early satiety and signs of malabsorption may also be present [12]. In an elderly patient with an underlying atherosclerosis, history of weight loss, and early satiety, chronic mesenteric ischemia should be strongly considered [28]. As with acute ischemia, clinical evaluation alone is insufficient for making the diagnosis of chronic ischemia, and imaging plays a key role for this purpose [67].


Imaging of Mesenteric Ischemia

Imaging of Mesenteric Ischemia. Radiography Abdomen Radiography has little to no role in the diagnosis of chronic mesenteric ischemia because these patients have not yet developed bowel necrosis, and therefore the radiograph will likely be normal or demonstrate nonspecific findings. A negative radiograph also does not exclude the diagnosis of chronic mesenteric ischemia [19,57,68]. CTA Abdomen and Pelvis CTA of the abdomen and pelvis has been shown to provide best accuracy and inter-reader agreement for grading mesenteric vessel stenosis compared to MRA and US, with sensitivity and specificity of 95% to 100% using DSA as a reference standard [29]. Moreover, CTA is an accurate diagnosing tool for detecting median arcuate ligament syndrome as a potential cause of chronic ischemia [7]. CTA can also accurately exclude other causes of chronic abdominal pain. CT Abdomen and Pelvis CT of the abdomen and pelvis with IV contrast performed during the venous phase appears to provide satisfactory evaluation of major vascular pathology, such as atherosclerotic plaques and occlusions, although this has not been well studied [69]. There is a paucity of data regarding performance of CT without IV contrast for suspected chronic mesenteric ischemia. Although able to assess the extent calcified atherosclerotic plaque affects the mesenteric vasculature, CT without IV contrast is limited in its ability to evaluate noncalcified plaque and is therefore likely to underestimate the degree of stenosis. Additionally, calcified atherosclerotic plaque in the mesenteric vasculature is a common incidental finding in the elderly population and cannot be relied upon for accurate diagnosis of chronic mesenteric ischemia [24,26,33]. CT without and with IV contrast is not indicated in the evaluation of suspected chronic mesenteric ischemia.


Crohn Disease

Crohn Disease.  Introduction/Background Crohn disease (CD) is a chronic inflammatory disorder involving the gastrointestinal tract, typically characterized by episodic flares and times of remission. Over the past several decades, there has been an increasing incidence of this disease [1-3]. Any portion of the gastrointestinal tract or alimentary tract may be involved, but the small bowel alone is affected in about a third of patients, the colon alone in a somewhat higher percentage of patients, and combined involvement of the colon and the small bowel is seen in less than a third of patients [4,5]. Perianal disease is another not uncommon manifestation [6]. Pathologically, CD is characterized by transmural granulomatous inflammation [7]. Although the bowel may return to normal after an acute flare, underlying structural damage progressively occurs over time with recurrent bouts of inflammation, leading to stricture formation, penetrating sinuses or fistulas, or a combination of the two [8]. The diagnosis of CD is based on a combination of clinical, laboratory, endoscopic, histological, and imaging findings [7,9]. No single diagnostic test allows unequivocal diagnosis. The imaging characteristics and distribution of disease provide supportive evidence for the diagnosis of CD. In addition, imaging is complementary to endoscopic techniques such as ileocolonoscopy, which allows diagnosis of disease when endoscopy is negative because of intramural disease without associated mucosal activity or because of a lack of colonic and distal ileal involvement [10]. Disease activity has been traditionally determined by clinical factors including patient symptoms and laboratory tests in which indices, such as Crohns Disease Activity Index, help to determine management. There is growing evidence, however, that active inflammation can exist despite clinical resolution of symptoms [11-13] and that complete mucosal healing represents a better treatment target for long-term outcomes than reliance on clinical symptoms [13].


Crohn Disease

Crohn Disease. In this regard, both endoscopy and imaging are becoming central tools in CD to detect such inflammation [13,14]. They are complementary in nature with differing advantages [9]. Colonoscopy with ileal intubation allows direct visualization of mucosal inflammation and ulceration and the possibility of biopsy. Cross- sectional imaging, such as CT enterography or MR enterography, allows evaluation of disease proximal to the ileum beyond the reach of the colonoscope as well as detection of transmural disease with overlying normal mucosa that may be not apparent at direct optical inspection. aPanel Chair, University of Wisconsin Hospital & Clinics, Madison, Wisconsin. bNewton-Wellesley Hospital, Newton, Massachusetts. cPanel Vice-Chair, University of California San Diego, San Diego, California. dUniversity of Texas Health Science Center at Houston and McGovern Medical School, Houston, Texas; American Gastroenterological Association. eVirginia Tech Carilion School of Medicine, Roanoke, Virginia. fMassachusetts General Hospital, Boston, Massachusetts. gMedstar Georgetown University Hospital, Washington, District of Columbia. hCleveland Clinic, Cleveland, Ohio. iCleveland Clinic, Cleveland, Ohio; American College of Emergency Physicians. jDuke University Medical Center, Durham, North Carolina. kEmory University, Atlanta, Georgia. lPenn State Health, Hershey, Pennsylvania. mUniversity of Alabama at Birmingham, Birmingham, Alabama. nJohns Hopkins Bayview Medical Center, Baltimore, Maryland. oUniversity of California San Francisco, San Francisco, California. pSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document.


Crohn Disease

Crohn Disease. Reprint requests to: publications@acr.org Crohn Disease which occurs with water, allowing for increased distal luminal distention. If the patient cannot tolerate the oral contrast requirements of the enterography technique, CT can still be performed but with a loss of sensitivity. Although positive oral contrast often obscures the presence of subtle inflammation, it has been shown to improve detection of potential complications related to ongoing CD, including abscess formation, fistula and sinus tract formation, compared with neutral agents [16]. Thus, in some circumstances, positive luminal contrast may be the preferred agent at a standard CT to detect such complications. CT enterography or MR enterography involves oral ingestion by the patient, whereas CT enteroclysis and MR enteroclysis involves placement of a nasoduodenal tube to allow oral contrast infusion directly into the small bowel at a predetermined rate. These procedures are more invasive and may not be well tolerated by acutely ill patients. The technical demands of the enteroclysis protocol related to placement of a nasoduodenal tube and the need for radiologist monitoring throughout the procedure have been negative impediments to widespread use. Bowel distention of the jejunum is typically less at enterography than at enteroclysis but is considered acceptable with good technique [17,18]. CT Enterography CT enterography represents a CT examination with a specialized protocol. Neutral contrast by mouth is given in large amounts over a set time to promote optimal distention of the small bowel [19-21]. Combined with other technical modifications, including thin collimation, multiplanar reconstruction, and intravenous (IV) contrast, this protocol maximizes the technique to depict inflammatory changes in the small bowel related to CD [20,22,23]. It is difficult to precisely determine the test characteristics in CD exactly because of the lack of a true reference standard.


Crohn Disease

Crohn Disease. However, the overall diagnostic performance for CT enterography is excellent. When an endoscopic standard is utilized, sensitivity for CD ranges from 75% to 90%, with a specificity of >90% [24-27]. Compared with other imaging modalities, CT enterography represents an optimal option for most patients [21,27-31]. The diagnosis of acute inflammation is made through visualization of thickened small bowel with mural stratification as well as extraenteric processes including engorged vasa recti/vasculature and surrounding inflammatory stranding [25,26,32-34]. Because CT enterography is a cross-sectional imaging modality, assessment for alternative diagnoses, as well for the possible complications of CD including obstruction, abscess, and fistula, can be made [28,35-37]. With its intrinsic high spatial resolution and reproducible quality, state-of-the-art CT enterography represents one of the main imaging methods for initial diagnosis of small-bowel CD. At many United States medical centers and practices, a combination of CT enterography and ileocolonoscopy has been advocated as the diagnostic algorithm of choice at initial presentation [38]. Ileocolonoscopy can assess for colonic and distal ileal involvement and permits biopsies. The addition of CT enterography allows for assessment of the entire small bowel, including the distal ileum, and is helpful in establishing a CD diagnosis in cases in which the terminal ileum and colon are not involved or when intramural disease is predominant, which may not be apparent at endoscopy. For this variant in which the patient does not have an established diagnosis for CD and other entities remain in the differential, the cross-sectional/global nature of this CT-based modality allows potential diagnosis of an entity mimicking a CD presentation and adds to the utility of CT enterography. Ultimately, the decision to select CT enterography versus a standard CT abdomen and pelvis examination is dependent on the acuity and severity of presentation.


Crohn Disease

Crohn Disease. For more indolent presentations in which the patient is able to tolerate large volumes of oral contrast, CT enterography is preferred because it is can detect more subtle findings of CD compared with a standard CT with positive oral contrast. In contrast, in the acute presentation in which the patient is severely ill and unable to tolerate the large volume requirements, a standard CT (without or with oral contrast) may be the preferred choice. Presumably, any findings of CD would not be subtle in this situation. Crohn Disease CT Abdomen and Pelvis Standard abdomen and pelvis CT with IV contrast with a routine protocol (ie, without neutral oral contrast enterography technique) can be useful in the initial presentation of a patient with CD without a known prior diagnosis, particularly in the instance of an acutely ill individual who may be unable to tolerate large amounts of oral contrast for an enterography protocol. Standard CT also allows for alternative diagnoses that may mimic CD such as appendicitis in this variant. This adds to the potential utility of this modality for this variant. However, if the patient is able to tolerate the oral contrast requirements of CT enterography, optimizing bowel technique improves examination performance over standard CT and should be preferred. Although standard abdomen and pelvis CT can be done either with or without the administration of IV contrast, it is evident that many of the processes, such as mural enhancement associated with CD require IV contrast for optimal assessment. Without IV contrast, such processes can only be inferred by associated findings, such as wall thickening, which may not occur in mild inflammation. In fact, the importance of contrast can be underscored by the emphasis on determining the optimal timing of imaging following IV contrast administration as opposed to comparisons between IV contrast and noncontrast CT [22]. A prior meta-analysis that evaluated CT performance included studies that were all conducted with IV contrast [25].


Crohn Disease

Crohn Disease. There is a clear consensus that noncontrast CT holds poorer performance compared against a CT with IV contrast. Standard CT abdomen and pelvis with IV contrast can provide evidence of inflammation of an affected gastrointestinal segment. Although there may be less than optimal bowel distention with positive luminal contrast (compared with volume loading techniques) and positive contrast may obscure subtle stratified mural enhancement and more subtle areas of active inflammation, CT with positive luminal contrast can identify wall thickening, luminal narrowing, and adjacent inflammatory changes that may be seen in CD [39]. In addition to assessing for inflammation, standard CT with IV contrast can also evaluate for CD complications, including bowel obstruction, fistula formation, and abscess formation, and positive luminal contrast is preferable to no oral contrast in this scenario. Sensitivities for CT-based evaluation for stenosis/obstruction range from 85% to 94% with very high specificities [40,41]. Sensitivities for abscesses are also very good, ranging from 86% to 100% [27,36]. There is more variable performance for fistula detection with sensitivities ranging from 68% to 100% [27,40,42]. One study showed a very low sensitivity of 20% for enteroenteric fistulas in their series [40]. Thus, in the acute setting, standard CT with IV contrast is a suitable option for assessment. On the other hand, if the patient is relatively well and able to tolerate the oral contrast requirements of CT enterography, the optimized bowel protocol increases sensitivity for more subtle inflammation. CT Enteroclysis CT enteroclysis is a CT-based examination in which a nasoduodenal tube is placed to allow controlled distention of the small bowel. Typically, neutral contrast is continuously infused into the small bowel during CT, and IV contrast is also given. This procedure typically allows for better distention of the small bowel compared with oral ingestion at CT enterography [43,44].


Crohn Disease

Crohn Disease. Because of the active infusion, stenoses are more readily determined [43]. There have been few studies evaluating performance in recent years. Although bowel distention of the jejunum is improved with CT enteroclysis, the distention at CT enterography is considered acceptable [17,18], and CT enterography has been more generally utilized over CT enteroclysis because the procedure is better tolerated by patients. As with all imaging modalities, it is difficult to precisely determine the test characteristics in CD exactly because of the lack of a true reference standard. However, the overall diagnostic performance for CT enteroclysis is excellent (ie, >85% sensitivity, >90% specificity) [45-47], and this examination has been used as a reference standard for other modalities in various studies [41,47]. The diagnosis of acute inflammation is made through visualization of thickened small bowel with mural stratification as well as extraenteric processes, including engorged vasa recti/vascular and surrounding inflammatory stranding [43,44]. Because CT enteroclysis is a cross- sectional imaging modality, assessment for alternative diagnoses as well as for the possible complications of CD, including obstruction, abscess, and fistula, can be made [43]. Although the bowel optimization at CT enteroclysis allows excellent examination performance, equivalent to highest-performing modalities, CT enteroclysis is not typically suitable in the acute setting in which the patient is ill. It is not uncommon that they cannot tolerate the requirements of this somewhat invasive examination. In a scenario in which the CD is a diagnostic consideration among others without a prior established diagnosis of inflammatory bowel disease, the discomfort and risks of duodenal intubation and active contrast infusion often outweighs the increased diagnostic performance gained, arguing against its use in this situation. Crohn Disease


Crohn Disease

Crohn Disease. MR Enteroclysis MR enteroclysis is a MR-based examination in which a nasoduodenal tube is placed to allow controlled distention of the small bowel. Typically, biphasic enteral contrast (low signal on T1 and high signal on T2) is infused over time prior to MRI, and IV contrast is given during the MR examination. The technical demands of this more invasive examination are greater but typically allow for better distention of the small bowel compared with oral ingestion with an enterography technique [48]. There have been few studies evaluating performance of this technique in recent years because it is not a widely utilized examination. Although bowel distention of the jejunum is typically less at enterography than with enteroclysis, distention achieved with enterography is considered acceptable [17] and has been more widely utilized compared with MR enteroclysis. As with all imaging modalities, it is difficult to precisely determine the test characteristics in CD exactly because of the lack of a true reference standard. However, the overall diagnostic performance for MR enteroclysis is excellent and at least equivalent to MR enterography [49]. One comparison study between these two modalities demonstrated statistically better detection of superficial mucosal abnormalities over MR enterography but no difference for stenoses and fistulas [50]. Although the bowel optimization at MR enteroclysis allows excellent examination performance, equivalent to the highest-performing modalities, MR enteroclysis is not typically suitable in the acute setting in which the patient is ill. Often, they cannot tolerate the requirements related to placement of the nasoduodenal tube and active infusion of contrast. In addition, the evaluation for alternative diagnoses mimicking CD may be more difficult or limited. MR Enterography MR enterography combines contrast-enhanced MRI scanning using fast imaging techniques with an enterography protocol to optimize bowel distension [38].


Crohn Disease

Crohn Disease. As described with CT enterography, this requires the patient to ingest a large volume of oral contrast in a set time. Additionally, the use of glucagon or prone imaging may help to decrease bowel peristalsis and thus artifact. MR enterography holds excellent test performance characteristics (see below) equivalent to other optimized modalities, such as CT enterography. The ability to diagnose alternative diagnoses may be decreased in cases when a CT-based option may be preferable, depending on the level of patient acuity and ability to hold still. Severely ill patients are less likely to be able to hold still for the duration of MRI examination, leading to increased artifact and poorer image quality. In addition, if ill, the patient may not be able to tolerate the required large volumes of contrast required at MR enterography. MRI Abdomen and Pelvis Standard MRI with a routine protocol (ie, MRI without and with IV contrast and without oral contrast enterography technique) can detect evidence of CD if the patient cannot tolerate large volumes of oral contrast (ie, acutely ill patients). However, the lack of bowel optimization technique decreases evaluation of more subtle findings. One study (n = 100) reported a sensitivity of 50% to 86% and specificity of 93% to 94% for wall thickening [73]. Thus, standard MR may be an option when oral contrast requirements at enterography cannot be tolerated. For CD complications, the diagnostic ability of MRI is similar to standard CT with IV with similar reported sensitivities and specificities in various series [27,40,58,72]. The sensitivity for stenosis/obstruction ranges from 87% to 92% with high specificities; detection performance remains high for abscesses, with sensitivity ranging from 86% to 100%. As with CT, the detection for fistulas is more variable, ranging from 40% to 100%. Because of


Crohn Disease

Crohn Disease. Crohn Disease the superior soft-tissue contrast, perianal disease including fistulation to the perineum is best evaluated at MRI, using a small field of view and focused examination [74-76]. Standard MRI without IV contrast has been investigated because of emerging concerns with IV gadolinium use and potential long-term accumulation in the body and brain. Noncontrast techniques, such as diffusion-weighted imaging (DWI), have been used to evaluate evidence for CD. There is growing literature examining its promise in detecting active disease versus quiescent disease for complication evaluation and disease monitoring, although many of the studies involve DWI in the context of enterography technique [77]. One study without enterography technique [48] reported a sensitivity of 49% to 82% and specificity of 85% to 93% for DWI, although lower specificities have been reported at meta-analysis [78]. Overall, DWI appears to have moderate sensitivity but low specificity leading to increased false positives for disease activity [77]. Thus, the current consensus is that noncontrast only techniques such as DWI can be done but there is likely improved performance with the information gained from post-IV contrast series. Severely ill patients are less likely to be able to hold still for the duration of an MRI examination, leading to increased artifact and poorer image quality. In these instances, other options may be preferable, particularly CT enterography or standard abdomen and pelvic CT. Radiography Abdomen Radiographs of the abdomen are limited in the initial diagnosis for CD. The ability to directly visualize bowel pathology is limited, and evidence for CD is instead inferred indirectly. Radiographs may be useful in severely ill presenting patients to evaluate for the presence of bowel perforation or obstruction.


Crohn Disease

Crohn Disease. Fluoroscopy Small-Bowel Follow-Through and Fluoroscopic Enteroclysis Historically, fluoroscopic contrast examinations of the gastrointestinal tract have been the primary imaging methods of choice in the diagnosis of CD. Small-bowel follow-through (SBFT; with or without per oral pneumocolon) and enteroclysis can be used to evaluate the small bowel for evidence of thickening and active disease [50,79]. In addition, internal fistulas can be detected [80], although other extramural complications, such as abscess formation, are only indirectly visualized, which leads to decreased detection [27]. It has become evident; however, with the emergence of specialized cross-sectional imaging modalities, that the performance of contrast fluoroscopy is not as accurate for active disease as compared to these other examinations [18,42,46,81,82]. Both SBFT and enteroclysis are hampered by their 2-D perspective, whereby pathology can be obscured because of overlapping bowel loops [18,82,83]. On the other hand, the real-time assessment for a fixed versus pliable nature of a segment of bowel can provide important ancillary information. Depending on institutional and surgeon preference, there may be a role in delineating the preoperative anatomy for the surgeon, although there has been a marked decline in fluoroscopic use over recent years. In addition, fluoroscopic examinations may not be tolerated in acutely ill patients because of the oral contrast requirements for these procedures. Fluoroscopy Contrast Enema Colonoscopy is the preferred initial examination of the colon in patients suspected of having inflammatory bowel disease primarily involving the colon as opposed to the small bowel [9]. Colonoscopy is superior to the barium enema for the detection of early inflammatory changes and has largely replaced it as the initial diagnostic examination [9]. Particularly in an acutely ill patient, a contrast enema may be technically challenging because of the need for retrograde contrast instillation. Crohn Disease


Crohn Disease

Crohn Disease. However, patient factors such as obesity and guarding, especially in the acutely ill scenario, may preclude adequate compression with the US probe. In addition, large amounts of shadowing gas may obscure bowel, preventing an optimal examination. Location of bowel involvement affects diagnosis with higher sensitivities for terminal ileal involvement detection as compared with more proximal small bowel disease [87]. False-positive diagnoses of abscesses are more likely at US [97]. The determination for alternative etiologies may also be decreased as compared with CT or MRI. HMPAO WBC Scan Leucoscintigraphy or Tc-99m-hexamethyl propylene amine oxime-labeled white blood cell (Tc-99m HMPAO WBC) scan have demonstrated good sensitivities and specificities for intestinal inflammation in the 79% to 85% and 81% to 98% range, respectively [98]. Proponents contend that leucoscintigraphy is useful in the diagnosis and evaluation of activity of extent of disease [99] with performance results equivalent to cross-sectional imaging [28]. However, the disadvantages of this examination, such as the decreased ability to depict and therefore detect alternative diagnoses and the complicated time-consuming technical aspects (ie, labeling and handling of blood products) have limited its use in initial diagnosis. Furthermore, leucoscintigraphy is limited in alternative diagnoses mimicking CD. FDG-PET/CT Skull Base to Mid-Thigh The addition of metabolic information from PET with the morphologic anatomic imaging of CT or MR shows promise. It may be helpful to better assess the level of active inflammation from fibrosis [100,101]. Studies also show improved assessment in the colon in a murine animal model [102], which points to potential future usefulness because the colon is less well evaluated at both CT enterography and MR enterography. At this point, there are few large-series published clinical studies but small series show promising results [103,104]. Variant 2: Known Crohn disease, suspected acute exacerbation.


Crohn Disease

Crohn Disease. In this clinical variant, there is an established diagnosis of CD. Here, the patient presents with acute worsening of symptoms attributable to known disease. The concern is for an active flare or for the development of a complication of CD (ie, obstruction, abscess, fistula development). The clinical suspicion of an alternative diagnosis mimicking CD is low. CT Abdomen and Pelvis Standard abdomen and pelvis CT with IV contrast with a routine protocol (ie, without oral contrast enterography technique) can be useful in the suspected exacerbation of CD. Although the imaging findings of an acute flare in a known CD patient are typically not subtle (ie, not the situation of subtle mucosal enhancement in a clinically asymptomatic patient undergoing treatment monitoring), optimizing the bowel by enterography technique leads to improved detection of inflammation and should be pursued if the patient can tolerate the oral contrast. On the other hand, CT with positive luminal contrast (without enterography technique) can identify wall thickening, luminal narrowing, and adjacent inflammatory changes that may be seen in CD [19]. In addition, the complications of abscess formation or fistula formation can be detected at standard IV contrast CT in which the positive oral contrast may improve detection of complications. Sensitivities for abscesses are very good, ranging from 86% to 100% [27,36]. There is more variable performance for fistula detection with sensitivities ranging from 68% to 100% [27,40,42]. One study showed a very low sensitivity of 20% for enteroenteric fistulas in their series [40]. Although standard abdomen and pelvis CT can be done either with or without the administration of IV contrast, it is evident that many of the processes seen with an acute flare in CD require IV contrast for optimal assessment. Without IV contrast, such processes can only be inferred by associated findings, such as wall thickening.


Crohn Disease

Crohn Disease. In fact, the importance of contrast can be underscored by the emphasis on determining the optimal timing of imaging following IV contrast administration as opposed to comparisons between IV contrast and noncontrast CT [22]. A prior meta-analysis that evaluated CT performance included studies that were all conducted with IV contrast [25]. There is clear consensus that noncontrast CT holds poorer performance compared against a CT with IV contrast. CT Enteroclysis CT enteroclysis is a CT-based examination in which a nasoduodenal tube is placed to allow controlled distention of the small bowel. Typically, neutral contrast is continuously infused into the small bowel during CT, and IV contrast is also administered. This procedure typically allows for better distention of the small bowel compared with oral ingestion at CT enterography [43,44]. Because of the active infusion, stenoses are more readily determined [43]. Crohn Disease The overall diagnostic performance for CT enteroclysis is excellent (ie, >85% sensitivity, >90% specificity) [45- 47], and this examination has been used as a reference standard for other modalities in various studies [41,47]. However, it is important to remember that detection of subtle evidence for CD is not needed in this clinical variant in which the patient is presenting acutely with a suspected flare or complication. Similar to other CT-based options, the assessment for the possible complications of CD, including obstruction, abscess, and fistula, can be made because of its underlying cross-sectional nature without additional advantage from the dedicated enteroclysis protocol. In this specific variant, CT enteroclysis may be limited because it is dependent on the clinical acuity or severity of presentation. With a significant acute flare or complication, the patient would poorly tolerate CT enteroclysis because of the marked demands on the patient related to the placement of the nasoduodenal tube and need for active infusion of oral contrast.


Crohn Disease

Crohn Disease. Here, the risks outweigh the added benefits of optimized bowel visualization, and this imaging choice should be avoided when acutely ill. If, however, the patient is relatively asymptomatic, CT enteroclysis may be an appropriate option with excellent diagnostic performance. CT Enterography CT enterography represents a CT examination with a specialized protocol. Neutral contrast by mouth is given in large amounts over a set time period to promote optimal distention of the small bowel [19-21]. Combined with other technical modifications, including thin collimation, multiplanar reconstruction, and IV contrast, this protocol maximizes the technique to depict inflammatory changes in the small bowel related to CD [20,22,23]. CT enterography is well suited to evaluate a potential acute flare or complication of CD. However, if the patient cannot tolerate the contrast requirements of the enterography technique, standard CT may be an option (although less sensitive, the findings of an acute flare are likely not subtle if the patient is acutely ill and unable to tolerate the contrast volume of CT enterography). The overall diagnostic performance for CT enterography is excellent. When an endoscopic standard is utilized, sensitivity for CD ranges from 75% to 90%, with a specificity of >90% [24-27]. The diagnosis of acute inflammation is made through visualization of thickened small bowel with mural stratification, as well as extraenteric processes that include engorged vasa recti/vasculature and surrounding inflammatory stranding [25,26,32-34]. Because CT enterography is a cross-sectional imaging modality, assessment for the possible complications of CD, including obstruction, abscess, and fistula, can be made similar to the ability of standard CT abdomen and pelvis [28,35-37]. Ultimately, the decision to select CT enterography versus a standard CT abdomen and pelvis is dependent on the ability to tolerate the oral contrast requirements of CT enterography.


Crohn Disease

Crohn Disease. CT enterography is more sensitive for bowel changes related to CD than standard CT given the oral contrast optimization. However, the findings of CD in an acute flare are often not subtle and can be seen at standard CT. In addition, the complications including abscess or fistula formation may be easier seen at standard CT with positive oral contrast. MR Enteroclysis MR enteroclysis is a MR-based examination in which a nasoduodenal tube is placed to allow controlled distention of the small bowel. Typically, biphasic enteral contrast (low signal on T1 and high signal on T2) is infused, and IV contrast is given. There have been few studies evaluating performance in recent years. The overall diagnostic performance for MR enteroclysis is excellent and at least equivalent to MR enterography [49]. One comparison study between these two modalities demonstrated statistically better detection of superficial mucosal abnormalities over MR enterography but no difference for stenoses and fistulas [50]. In this specific variant, MR enteroclysis may be limited dependent on the clinical acuity or severity of presentation. With a significant acute flare or complication, the patient would poorly tolerate MR enteroclysis because of the marked demands on the patient related to the placement of the nasoduodenal tube and need for active infusion of oral contrast. Here, the risks outweigh the added benefits of optimized bowel visualization, and this imaging choice should be avoided when acutely ill. In addition, patients are likely unable to hold still, leading to increased artifact and poorer image quality. If, however, the patient is relatively asymptomatic, MR enteroclysis may be an appropriate option with excellent diagnostic performance. MR Enterography MR enterography combines contrast-enhanced MRI scanning using fast imaging techniques with an enterography protocol to optimize bowel distension [38].


Crohn Disease

Crohn Disease. As described with CT enterography, this requires the patient to ingest a large volume of oral contrast in a set time period. Additionally, the use of glucagon or prone imaging may help to Crohn Disease decrease bowel peristalsis and thus artifact. MR enterography holds excellent test performance characteristics (see below) equivalent to other optimized modalities, such as CT enterography. The performance of MR enterography for CD is very good. Rates of sensitivity and specificity are 77% to 82% and 80% to 100%, respectively [24,66,67]; MR enterography can accurately display bowel-wall changes in CD [51-54]. Characteristic bowel-wall changes suggesting active inflammation include bowel-wall thickening, high T2 mural signal, mural hyper enhancement with mural stratification, and hyperemic vasa recta [55-64]. MR cine imaging is potentially useful, allowing for assessment of decreased bowel motility in the affected segments with CD [65]. Besides inflammation, MRI can detect complications for CD that include obstruction, abscess, or fistula. Test performance characteristics for complications are similar to CT enterography [27,28,35,40,68,69]. Overall, MRI is more prone to respiratory and bowel-motion artifact, despite the use of glucagon, which may lead to suboptimal examinations and more difficult interpretations. MRI Abdomen and Pelvis Standard MRI with a routine protocol (ie, MRI without and with IV contrast and without oral contrast enterography technique) can detect evidence of CD if the patient cannot tolerate large volumes of oral contrast. However, the lack of bowel optimization decreases evaluation of inflammation compared with MR enterography with optimized bowel technique. One study (n = 100) reported a sensitivity of 50% to 86% and specificity of 93% to 94% for wall thickening [73]. For CD complications, the diagnostic ability of MRI is similar to its CT counterpart with similar reported sensitivities and specificities in various series [27,40,58,72].


Crohn Disease

Crohn Disease. The sensitivity for stenosis/obstruction ranges from 87% to 92% with high specificities; detection performance remains high for abscesses, with sensitivity ranging from 86% to 100%. As with CT, the detection for fistulas is more variable, ranging from 40% to 100%. Because of the superior soft-tissue contrast, perianal disease, including fistulation to the perineum, is best evaluated with MRI, using a small field of view, focused examination [74-76]. Standard MRI without IV contrast has been investigated because of emerging concerns with IV gadolinium use and potential long-term accumulation in the body and brain. Noncontrast techniques such as DWI have been used to evaluate evidence for CD. There is growing literature examining its promise in detecting active disease versus quiescent disease, for complication evaluation, and disease monitoring, although many of the studies involve DWI in the context of enterography technique [77]. One study without enterography technique [48] reported a sensitivity of 49% to 82% and specificity of 85% to 93% for DWI, although lower specificities have been reported at meta- analysis [78] Overall, DWI appears to have moderate sensitivity but low specificity, leading to increased false positives for disease activity [77]. Thus, the current consensus is that noncontrast-only techniques such as DWI can be done, but there is likely improved performance with the information gained from post-IV contrast series. In this specific variant, MR may be limited. Acutely ill patients are less likely to be able to hold still for the duration of an MRI examination, leading to increased artifact and poorer image quality. In these instances, other options may be preferable, particularly CT enterography or standard abdomen and pelvic CT. However, patient factors such as obesity and guarding may not allow adequate compression with the US probe or large amounts of shadowing gas may obscure bowel, preventing an optimal examination.


Crohn Disease

Crohn Disease. Location also affects diagnosis in which higher sensitivities for terminal ileal involvement are seen compared with more proximal small bowel [87]. False-positive diagnoses of abscesses are more likely at US [97]. Radiography Abdomen Radiographs of the abdomen are limited in the evaluation of an acute flare or complication of CD. The ability to directly visualize bowel pathology is limited, and evidence for CD is instead inferred indirectly. There is little role for radiographs if the patient is not acutely ill. Radiographs may be useful in severely ill presenting patients for presence of bowel perforation or evidence for obstruction. Crohn Disease Fluoroscopy Small-Bowel Follow-Through and Fluoroscopic Enteroclysis Historically, fluoroscopic contrast examinations of the gastrointestinal tract have been the primary imaging methods of choice in the evaluation of CD. SBFT (with or without per oral pneumocolon) and enteroclysis can be used to evaluate the small bowel for evidence of thickening and active disease [50,79]. In addition, internal fistulas can be detected [80], although other extramural complications, such as abscess formation are only indirectly visualized, which leads to decreased detection [27]. It has become evident; however, with the emergence of specialized cross- sectional imaging modalities, that the performance of contrast fluoroscopy is not as accurate for active disease compared with these other examinations [18,42,46,81,82]. Both SBFT and enteroclysis are hampered by their 2-D perspective, whereby pathology can be obscured because of overlapping bowel loops [18,82,83]. On the other hand, the real-time assessment for a fixed versus pliable nature of a segment of bowel can provide important ancillary information. Depending on institutional and surgeon preference, there may be a role in delineating the preoperative anatomy for the surgeon, although there has been a marked decline in fluoroscopic use over recent years.


Crohn Disease

Crohn Disease. Fluoroscopy Contrast Enema Colonoscopy is the preferred examination of the colon in patients suspected of having inflammatory bowel disease [9]. It is superior to the barium enema for the detection of early inflammatory changes and has largely replaced it as the initial diagnostic examination [9]. Although contrast enemas can detect fistulas to other organs and sinus tracts, it is poor for abscess determination given its non-cross-sectional nature. HMPAO WBC Scan Leucoscintigraphy, or Tc-99m-HMPAO WBC scan, have demonstrated good sensitivities and specificities for intestinal inflammation in the 79% to 85% and 81% to 98% range, respectively [98]. Proponents contend that leucoscintigraphy is useful in the diagnosis and evaluation of activity and extent of disease [99] with performance results equivalent to cross-sectional imaging [28]. However, the disadvantages of this examination, such as the decreased ability to depict and therefore detect alternative diagnoses and the complicated time-consuming technical aspects (ie, labeling and handling of blood products), have limited its use in evaluation. FDG-PET/CT Skull Base to Mid-Thigh The addition of metabolic information from PET with the morphologic anatomic imaging of CT or MR shows promise. It may be helpful to better assess the level of active inflammation from fibrosis [100,101]. Studies also show improved assessment in the colon in a murine animal model [102], which points to potential future usefulness because the colon is less well evaluated with both CT enterography and MR enterography. At this point, there are few large-series published clinical studies, but small series show promising results [103,104]. Variant 3: Known Crohn disease, disease surveillance; monitoring therapy. In this clinical scenario, the purpose of the imaging evaluation is to determine the presence or absence of disease activity in a relatively well CD patient (ie, mildly symptomatic to asymptomatic) in order to help determine medical management.


Crohn Disease

Crohn Disease. This is important because promoting situations of complete mucosal healing has been associated with sustained clinical remission, reduced hospitalization rates, and decreased need for surgery [12,13,105]. As with endoscopy, imaging may better direct treatment based on objective findings because it is known that subjective symptomatology and other clinical parameters have shown poor correlation with disease activity [106]. Secondly, when CD strictures are detected, imaging can help determine whether the narrowing is predominantly due to active inflammation or due to fibrosis. This distinction is critical because the former responds to medical interventions, whereas the latter would be better treated surgically. Because of the cost and significant complications of agents such as infliximab, empiric treatment with these agents to make this distinction (ie, does treatment improve the stenosis) is less attractive. CT Abdomen and Pelvis Standard abdomen and pelvis CT with IV contrast with a routine protocol (ie, without oral contrast enterography technique) can detect evidence for active CD. CT with positive luminal contrast can identify wall thickening, luminal narrowing, and adjacent inflammatory changes that may be seen in CD [39]. However, mucosal enhancement is obscured and subtle enhancement may be missed without the bowel optimization present with enterography technique. The decreased performance compared against other modalities with optimized bowel protocol would argue against its use in this clinical variant in which the patient is relatively well and able to tolerate the increased oral contrast volumes. Standard abdomen and pelvis CT without IV contrast is further hampered when evidence of increased vascularity seen with IV contrast use is not available. Crohn Disease CT Enteroclysis CT enteroclysis is a CT-based examination in which a nasoduodenal tube is placed to allow controlled distention of the small bowel. Typically, neutral contrast is infused and IV contrast given.


Crohn Disease

Crohn Disease. Because of the active infusion, stenoses are more easily determined [43]. There have been few studies evaluating performance in recent years. The overall diagnostic performance for CT enteroclysis is excellent (ie, >85% sensitivity, >90% specificity) [45-47], and this examination has been used as a reference standard for other modalities in various studies [41,47]. The diagnosis of acute inflammation is made through visualization of thickened small bowel with mural stratification as well as extraenteric processes, including engorged vasa recti/vasculature and surrounding inflammatory stranding [43,44]. Similar to CT enterography, the ability to detect even mild inflammation makes it useful in monitoring therapy. CT enteroclysis has been shown to be helpful in assessing the status of disease in CD patients post resection at the anastomosis [107]. However, the determination between active disease and fibrosis in a stricture remains difficult based on enhancement characteristics only [108]. Because CT enteroclysis is a cross- sectional imaging modality, assessment for alternative diagnoses as well for the possible complications of CD including obstruction, abscess, and fistula can be made [43]. Although CT enteroclysis represents one of the modalities with highest disease detection capabilities, the invasive nature with nasoduodenal tube insertion and active infusion of contrast may make it less favorable from a patient perspective, unless a mild stricture without definite proximal dilation is the clinical question and active distention is needed to confirm this stricture [9]. In addition, the need for repeated examinations over time makes this a less attractive choice in this clinical variant. CT Enterography CT enterography represents a CT examination with a specialized protocol. Neutral contrast by mouth is given in large amounts over a set time period to promote optimal distention of the small bowel [19-21].


Crohn Disease

Crohn Disease. Combined with other modifications, including thin collimation, multiplanar reconstruction, and IV contrast, this protocol maximizes the technique to depict inflammatory changes in the small bowel related to CD [20,22,23]. Although the diagnostic performance is excellent (see below), the need for repeated examinations over time makes this a less attractive choice in this clinical variant. The overall diagnostic performance for CT enterography is excellent. When an endoscopic standard is utilized, sensitivity for CD ranges from 75% to 90%, with a specificity of >90% [24-27]. The diagnosis of acute inflammation is made through visualization of thickened small bowel with mural stratification as well as extraenteric processes including engorged vasa recti/vasculature and surrounding inflammatory stranding [25,26,32-34]. Because of an excellent performance profile, CT enterography is able to assess for mucosal healing similar to MR enterography to help guide therapy [109]. One series (n = 63) demonstrated that CT enterography was able to detect wall changes, and influenced the treatment of CD patients [110]. However, regarding strictures, CT enterography has been considered poor in its ability to distinguish between active and fibrotic contributions to the stricture based on the presence or absence of above-mentioned findings (ie, mural hyper enhancement, thickening, engorged vasa recta, surrounding soft tissue thickening, etc) [108]. MR Enteroclysis MR enteroclysis is a MR-based examination in which a nasoduodenal tube is placed to allow controlled distention of the small bowel. Typically, biphasic enteral contrast (low signal on T1 and high signal on T2) is infused, and IV contrast is given. There have been few studies evaluating performance in recent years. The overall diagnostic performance for MR enteroclysis is excellent and at least equivalent to MR enterography [49].


Crohn Disease

Crohn Disease. One comparison study between these two modalities demonstrated statistically better detection of superficial mucosal abnormalities over MR enterography but no difference for stenoses and fistulas [50]. In this specific variant, MR enteroclysis theoretically holds the same advantages as outlined for MR enterography because the difference between the two is related to active distention via the nasoduodenal tube at MR enteroclysis versus distention from oral ingestion at MR enterography. Thus, the ability to evaluate mucosal healing as well as assessment of strictures for active disease versus fibrosis as documented at MR enterography should be equivalent at MR enteroclysis [48]. However, the invasive nature with nasoduodenal tube insertion and active infusion of contrast may make it less favorable from a patient perspective, unless a mild stricture without proximal dilation is the clinical question and active distention is needed to confirm this stricture [9]. MR Enterography MR enterography combines contrast-enhanced MRI scanning using fast imaging techniques with an enterography protocol to optimize bowel distension [38]. Similar to the case of CT enterography, this bowel optimization Crohn Disease technique requires the patient to ingest a large volume of oral contrast in a set time period. Additionally, the use of glucagon or prone imaging may help to decrease bowel peristalsis and thus artifact. MR enterography represents an ideal modality for repeated use to monitor therapy given its excellent test characteristics. Given the relatively well status of the patient, they are often able to hold still, and quality examinations are more likely to be consistently obtained. The performance of MR enterography for CD is very good. Rates of sensitivity and specificity are 77% to 82% and 80% to 100%, respectively [24,66,67]; MR enterography can accurately display bowel-wall changes in CD [51-54].


Crohn Disease

Crohn Disease. Characteristic bowel-wall changes suggesting active inflammation include bowel-wall thickening, high T2 mural signal, mural hyper enhancement with mural stratification, and hyperemic vasa recta [55-64]. MR cine imaging is potentially useful, allowing for assessment of decreased bowel motility in the affected segments with CD [65]. Besides inflammation, MRI can detect complications for CD including obstruction, abscess, or fistula. Test performance characteristics for complications are similar to CT enterography [27,28,35,40,68,69]. MR enterography has been shown to correlate with response to therapy and mucosal healing [111,112]. One prospective multicenter study (n = 48) showed 90% accuracy of ulcer healing determination at MR enterography, utilizing ileocolonoscopy as the reference standard [113]. In addition, MR is able to utilize natural tissue contrast at T2W imaging to help in the determination between active inflammation and fibrosis, which is not possible with CT-based modalities. DWI, magnetization transfer imaging, and cine sequences at MR enterography can also be helpful. [111]. MR enterography without IV contrast has been investigated because of emerging concerns with IV gadolinium use and potential long-term accumulation in the body and brain. Noncontrast techniques such as DWI have been used to evaluate evidence for CD. There is growing literature examining its promise in detecting active disease versus quiescent disease for complication evaluation and disease monitoring [77]. Overall, DWI appears to have moderate sensitivity but low specificity, leading to increased false positives for disease activity [77]. Thus, the current consensus is that noncontrast only techniques such as DWI can be done but there is likely improved performance with the information gained from post IV contrast series.


Crohn Disease

Crohn Disease. MRI Abdomen and Pelvis Standard MRI with a routine protocol (ie, without and with IV contrast and without oral contrast enterography technique) can detect evidence of CD if the patient cannot tolerate large volumes of oral contrast. However, the lack of bowel optimization decreases evaluation of inflammation. Thus, the key question of quiescent disease versus low levels of continuing inflammation central to this variant is not answered to the same confidence as with MR enterography (with optimized bowel technique). One study (n = 100) reported a sensitivity of 50% to 86% and specificity of 93% to 94% for wall thickening [73]. The literature on mucosal healing and MR has centered on MR enterography as opposed to standard MR without enterography protocol. MR enterography has been shown to correlate with response to therapy and mucosal healing [111,112]. One prospective multicenter study (n = 48) showed 90% accuracy of ulcer healing determination at MR enterography, utilizing ileocolonoscopy as the reference standard [113]. In this specific clinical scenario, the patient is typically able to tolerate enterography technique, and consequently, bowel optimization should be undertaken as opposed to standard MRI for this situation. For CD complications, the diagnostic ability of MRI is similar to its CT counterpart with similar reported sensitivities and specificities in various series [27,40,58,72]. The sensitivity for stenosis/obstruction ranges from 87% to 92% with high specificities; detection performance remains high for abscesses, with sensitivity ranging from 86% to 100%. As with CT, the detection for fistulas is more variable, ranging from 40% to 100%. Because of the superior soft-tissue contrast, perianal disease including fistulation to the perineum is best evaluated at MRI, using a small field-of-view, focused examination [74-76]. Standard MRI without IV contrast has been investigated because of emerging concerns with IV gadolinium use and potential long-term accumulation in the body and brain.


Crohn Disease

Crohn Disease. Noncontrast techniques such as DWI have been used to evaluate evidence for CD. There is growing literature examining its promise in detecting active disease versus quiescent disease for complication evaluation and disease monitoring, although many of the studies involve DWI in the context of enterography technique [77]. One study without enterography technique [48] reported a sensitivity of 49% to 82% and specificity of 85% to 93% for DWI, although lower specificities have been reported at meta- analysis [78]. Overall, DWI appears to have moderate sensitivity but low specificity, leading to increased false positives for disease activity [77]. Thus, the current consensus is that noncontrast only techniques such as DWI can Crohn Disease be done, but there is likely improved performance with the information gained from post IV contrast series. This reason, as well as the lack of a bowel distention optimization protocol, makes standard MRI without IV contrast less useful in this clinical variant. US Abdomen and Pelvis Transabdominal US can be effective option in CD [84,85]. However, in this variant, it may not be optimal given that areas of the abdomen may not be assessed because of shadowing bowel. However, there is emerging literature that US may be useful in therapy monitoring of CD patients [114,115]. In addition, contrast-enhanced US may be helpful in distinguishing between inflammatory and fibrotic disease [95]. Patient factors such as obesity and guarding may not allow adequate compression with the US probe or large amounts of shadowing gas may obscure bowel, preventing an optimal examination. Location also affects diagnosis in which higher sensitivities for terminal ileal involvement are seen compared to more proximal small bowel [87]. False positive diagnoses of abscesses are more likely at US [97]. Radiography Abdomen Radiographs of the abdomen are limited in the evaluation for CD.


Crohn Disease

Crohn Disease. The ability to directly visualize bowel pathology is limited, and evidence for CD is instead inferred indirectly. There is little role for radiography in this clinical variant. Fluoroscopy Small-Bowel Follow-Through Historically, fluoroscopic contrast examinations of the gastrointestinal tract have been the primary imaging methods of choice in the evaluation of CD. SBFT (with or without per oral pneumocolon) and enteroclysis can be used to evaluate the small bowel for evidence of thickening and active disease [50,79]. In addition, internal fistulas can be detected [80], although other extramural complications such as abscess formation are only indirectly visualized, which lead to decreased detection [27]. It has become evident; however, with the emergence of specialized cross sectional imaging modalities, that the performance of contrast fluoroscopy is not as accurate for active disease as compared with these other examinations [18,42,46,81,82]. Thus, there is little evidence to support its use in this specific clinical variant in which the inflammation may be very subtle. Both SBFT and enteroclysis are hampered by their 2-D perspective, whereby pathology can be obscured because of overlapping bowel loops [18,82,83]. On the other hand, the real-time assessment for a fixed versus pliable nature of a segment of bowel can provide important ancillary information. Dependent on institutional and surgeon preference, there may be a role in delineating the preoperative anatomy for the surgeon, although there has been a marked decline in fluoroscopic use over recent years. Fluoroscopy Contrast Enema Colonoscopy is the preferred initial examination of the colon in patients suspected of having inflammatory bowel disease [9]. It is superior to the barium enema for the detection of early inflammatory changes and has largely replaced it as the diagnostic examination [9].


Dementia

Dementia.  Introduction/Background Degenerative disease of the central nervous system is a growing public health concern. The prevalence of dementia, one of the leading degenerative conditions, is expected to quadruple by 2050 [1]. Other degenerative diseases may affect the extrapyramidal system and the motor system. Dementia is characterized by a significant loss of function in multiple cognitive domains without affecting the general level of arousal. Several forms are now recognized, including Alzheimer disease (AD), frontotemporal dementia (FTD), Lewy bodies disease, vascular dementia (VaD), and mixed dementias [2]. Although the causes of most dementias remain elusive, genetic research has opened many frontiers to understanding the pathophysiology of heretofore enigmas such as AD [1,3]. Additionally, infectious, autoimmune, and toxic etiologies have become increasingly more appreciated as causes of cognitive decline. Trauma with brain injury may also be associated with premature dementia. AD dementia is part of a continuum of clinical and biological phenomena. The workgroup emphasizes that AD dementia is fundamentally a clinical diagnosis. To make a diagnosis of AD dementia with biomarker support, the core clinical diagnosis of AD dementia must first be satisfied. In these recommendations, the term mild cognitive impairment (MCI) that is due to AD is used to refer to the symptomatic predementia phase of AD [5]. Similar to AD dementia, MCI that is due to AD cannot be currently diagnosed by a laboratory test but requires the judgment of a clinician. In addition, similar to AD dementia, etiologies in addition to AD pathophysiological processes may coexist in an individual that meets the criteria for MCI that is due to AD but in whom the AD pathophysiological process is the main cause of the cognitive dysfunction.


Dementia

Dementia. The stage of preclinical AD precedes MCI and encompasses the spectrum of presymptomatic autosomal dominant mutation carriers, asymptomatic biomarker-positive older individuals at risk for progression to MCI that is due to AD and AD dementia, as well as biomarker-positive individuals who have demonstrated a subtle decline from their own baseline that exceeds the expected in typical aging but would not yet meet criteria for MCI [6]. aColumbia University Medical Center, New York, New York. bUT Southwestern Medical Center, Dallas, Texas. cResearch Author, Emory University, Atlanta, Georgia. dPanel Chair, Montefiore Medical Center, Bronx, New York. eUC San Diego Health, San Diego, California. fOttawa Hospital Research Institute and the Department of Radiology, The University of Ottawa, Ottawa, Ontario, Canada; Canadian Association of Radiologists. gMCVH-Virginia Commonwealth University, Richmond, Virginia; Neurosurgery Expert. hUniversity of Kansas Medical Center, Kansas City, Kansas. iEinstein Healthcare Network, Philadelphia, Pennsylvania. jUniversity of California San Diego Medical Center, San Diego, California. kOregon Health & Science University, Portland, Oregon. lUniversity of North Carolina School of Medicine, Chapel Hill, North Carolina; American Academy of Neurology. mSheppard Pratt Health System, Towson, Maryland; American Psychiatric Association. nNorthwestern University Feinberg School of Medicine, Chicago, Illinois; Neurosurgery Expert. oWalter Reed National Military Medical Center, Bethesda, Maryland. pColumbia University Medical Center, New York, New York. qSpecialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels.


Dementia

Dementia. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: publications@acr.org In persons who meet the core clinical criteria for probable AD dementia, biomarker evidence may increase the certainty that the basis of the clinical dementia syndrome is the AD pathophysiological process. The recommendations of the working group did not advocate the use of AD biomarker tests for routine diagnostic purposes [4]. However, this opinion was refined in the 2014 position paper from the International Working Group- 2, which proposed that the diagnosis of AD required an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological marker consistent with AD pathology (including increased tracer retention on amyloid PET), moving amyloid PET into the diagnostic realm. The biomarkers of downstream neuronal injury, such as volumetric MRI and FDG-PET, were considered agents to measure or monitor the course of disease but not for initial diagnosis [8]. The primary role of neuroimaging in the workup of patients with probable or possible AD has typically been to exclude other significant intracranial abnormalities. In general, the imaging findings in structural studies such as MRI are nonspecific but may suggest other forms of dementia. The American Academy of Neurology (AAN) has recommended that the routine use of structural neuroimaging, such as a noncontrast CT or MRI examination, may assist with the diagnosis of dementia [9]. Advanced methods, such as volumetric MRI, amyloid PET, and FDG- PET, are not routinely used in community or general practices for the diagnosis or differentiation of forms of dementia [10-12]. CT Head Noncontrast CT head is used as a primary examination to exclude treatable lesions like a mass or subdural hematoma [9].


Dementia

Dementia. Although not as accurate as MRI, CT also permits detection of hippocampal atrophy in AD patients [13] but is not recommended as first-line imaging for this purpose because MRI provides higher resolution images. Contrast- enhanced CT head is not recommended because the examination is mainly used to rule out other pathologies that do not typically require contrast for detection. Similarly, dual-phase CT head is not indicated in the evaluation of AD. However, amyloid PET may be positive in cognitively normal subjects who do not develop AD and in patients with other forms of non-AD dementia [22]. Although a negative amyloid PET scan likely means a low probability of AD, the patient may still harbor a non-AD neurodegenerative condition. The Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association has proposed guidelines for the use of amyloid PET [23,24]. The taskforce suggests that amyloid PET may be useful and appropriate in patients with a cognitive complaint and confirmed impairment when AD is in the differential but the diagnosis is uncertain after evaluation by a dementia expert and the knowledge of the presence or absence of amyloid deposition is felt to add to patient care (although currently no treatment can slow AD progression, and the presence of amyloid cannot be sufficiently predictive in many cases). The taskforce cites specific appropriate use criteria in which amyloid PET might be useful: persistent or progressive unexplained MCI, possible AD (unclear clinical presentation, atypical clinical course or etiologically mixed presentation, and Dementia A CMS-convened Medicare Evidence Development and Coverage Advisory Committee that met in 2013 concluded there was low to intermediate confidence that amyloid PET would significantly contribute to the care of these patients. However, in its national coverage decision, CMS concluded that amyloid PET would be covered under a coverage with evidence development program [25].


Dementia

Dementia. According to the practice parameter for amyloid brain PET that was developed collaboratively by the ACR and the American Society for Neuroradiology (ASNR) [26], indications for amyloid PET mirror those of the amyloid imaging taskforce as above. FDG-PET/CT Brain PET imaging in dementia can be divided into metabolic PET, which uses FDG as a marker for metabolism, and amyloid PET, which uses agents that bind to amyloid deposits within the brain. FDG-PET imaging has been shown to provide greater diagnostic accuracy when compared with clinical evaluations without functional neuroimaging [27]. Hypometabolism on FDG-PET is thought to be related to decreased synaptic activity and is a biomarker of neurodegeneration or neuronal injury [12]. FDG-PET shows characteristic reductions of regional glucose metabolic rates in patients with probable and definite AD in the parietal, temporal, and posterior cingulate regions [28]. FDG- PET accurately discriminates AD patients from normal subjects with a sensitivity of 96% and specificity of 100% [28]. CMS has made FDG-PET available to Medicare recipients to assist with the diagnosis of dementia in the appropriate clinical setting (eg, to distinguish AD from FTD) in recognition of this usefulness [27]. A practice parameter for FDG-PET/CT for patients with cognitive decline has been developed collaboratively by the ACR-ASNR [26]. The qualifications and responsibilities of the personnel conducting the study and the standardized patient preparation, positioning, and protocol are also outlined in this document. An important detail to be emphasized is that the study should be performed at the request of physicians knowledgeable in clinical diagnosis and management of dementia and under circumstances in which the results of the examination are likely to impact patient care [26].


Dementia

Dementia. MR Spectroscopy Head MR spectroscopy may permit identification of mild to moderate AD with a specificity and sensitivity that suggests the potential for clinical usefulness and may predict the conversion of MCI to dementia [29]. Studies of automated MR spectroscopy for AD diagnosis have reported high sensitivity and moderate specificity. Findings in reported studies have varied, but decreased N-acetylaspartate (NAA) and increased myoinositol (mI) with the use of the NAA:mI ratio show the greatest promise [30]. However, prospective studies are lacking to validate this method for diagnosing AD. MRI Functional (fMRI) Head Recently tested as an imaging biomarker in AD is MRI functional (fMRI) because it may provide information about functional integrity of brain networks supportive memory and other cognitive domains [31]. Both conventional task-based fMRI and resting state fMRI (particularly the default mode network) [32] show promise as diagnostic markers but have not yet been subjected to a thorough validation. Most of the fMRI studies are single-center studies with small numbers of patients and limited test, retest, and cross-scanner reproducibility, limiting its use in the diagnosis of AD. MRI Head The primary role of neuroimaging in the workup of patients with probable or possible AD has typically been to exclude other significant intracranial abnormalities. A noncontrast MRI examination will assist with the diagnosis Dementia of dementia by excluding structural pathology like tumors or subdural hematomas [9]. Contrast-enhanced MRI is not needed in the initial imaging evaluation in dementia patients. Volumetric MRI can be used as a second-line imaging test for aiding in the diagnosis once the patient has been seen by a specialist. Medial temporal lobe atrophy has been noted to correlate with cognitive decline and nonfunctional test accumulation and is seen in patients with MCI compared with normal patients.


Dementia

Dementia. Atrophy measures can be a visual rating system (Scheltens score) [33], semiautomated, or automated volumetric techniques. Whole-brain and hippocampal atrophy rates are sensitive markers of progression of neurodegeneration and are increasingly used as surrogate outcomes in trials of potentially disease-modifying drugs. Volumetric MRI, along with FDG-PET and high CSF tau, is felt to be a biomarker of neurodegeneration or neuronal injury and could be able to document and follow disease severity [10,34]. In an evidence-based review of dementia diagnosis, the AAN did not recommend routine quantitative volumetry of the hippocampus or the entorhinal cortex because these techniques are labor intensive [9]. Diffusion-weighted imaging/apparent diffusion coefficient [35,36] and magnetization transfer imaging [37] are all either sensitive to early change or can add complementary information to atrophy measures but are second-line imaging tests. HMPAO SPECT or SPECT/CT Brain Regional cerebral blood flow determined using single-photon emission computed tomography (SPECT) imaging with Tc-99m hexamethylpropyleneamine oxime (HMPAO) shows bilateral temporoparietal or hippocampal hypoperfusion in patients with AD. Whether brain SPECT contributes substantially to diagnostic accuracy after a careful clinical examination using current diagnostic criteria is controversial. Although perfusion MRI is promising, SPECT remains superior in identifying pathologic perfusion [38]. An evidence-based review performed by the AAN concluded that SPECT imaging cannot be recommended for either the initial assessment or to clarify the differential diagnosis of suspected dementia because it has not demonstrated superiority to clinical criteria [9]. When compared with FDG-PET, SPECT has a lower diagnostic accuracy and is inferior in its ability to separate healthy controls from patients with true dementia [39,40]. Variant 2: Suspected frontotemporal dementia. Initial imaging. FTD is a neurodegenerative disorder that may be mistaken for AD.


Dementia

Dementia. Pathologically, it includes a heterogeneous group of sporadic and familial neuropsychiatric disorders. Pick disease is one of the neuropathological entities of FTD. Unlike AD, which increases in frequency with age, FTD is rare after the age of 75. Although the diagnosis of FTD is primarily clinical, neuroimaging serves several purposes: exclusion of other structural brain abnormalities that could clinically mimic FTD, differentiation of FTD from other neurodegenerative disorders (most commonly AD), and classification of the known subtypes of FTD [43]. Multimodal imaging is a promising approach in neuroimaging of FTD. Integrated PET/MRI systems allow a combination of structural and functional imaging in one examination that can increase sensitivity and specificity of these modalities in a smaller cohort of patients and thus may represent a method of choice in FTD [44]. CT Head Noncontrast CT head is used to exclude other lesions that may clinically mimic the disease. CT head with intravenous (IV) contrast or dual-phase imaging is not needed for initial evaluation. Dementia Amyloid PET/CT Brain Use of amyloid PET in FTD is limited to the exclusion of underlying amyloid brain pathology that can be seen in cases of AD with atypical presentation. PET tracers specific for tau protein deposits in the brain are currently being investigated, but no systematic studies on their application in FTD have been published [44]. FDG-PET/CT Brain FDG-PET is an established tool for differentiating FTD and AD and classifying different FTD subtypes. FDG-PET has a sensitivity of 60% and a positive predictive value of 78.5% for differentiating the subtypes of FTD [44]. The CMS coverage decision for payment for FDG-PET brain, in 2004, was based on FDG brain PET being a very valuable diagnostic study to differentiate AD and FTD in patients with documented cognitive decline of at least 6 months and a recently established diagnosis of dementia [45].


Dementia

Dementia. MR Spectroscopy Head MR spectroscopy metabolite changes in FTD are similar to the changes encountered in AD: lower NAA to creatine (Cr) ratio (NAA/Cr) and higher mI to Cr ratio (mI/Cr) than normal, but findings are more commonly centered on the frontal cortex in early FTD [46]. MR spectroscopy could be a helpful secondary test in patients who have clinical findings of FTD, but it is not a first-line imaging test. MRI Functional (fMRI) Head Brain activation has been shown to be significantly decreased in FTD in the frontal and parietal lobes compared with AD [47]. Resting state fMRI demonstrates alterations in structural and functional connectivity in presymptomatic FTD [48]. However, fMRI remains in the realm of research and is not recommended in routine evaluation of FTD. MRI Head MRI of the brain without IV contrast serves as a first-line imaging test to exclude secondary causes of symptoms such as subdural hematoma and tumor in patients with suspected FTD. IV contrast is not necessary for initial evaluation. Volumetric MRI has a second-level role in diagnosis and has been actively studied as a tool to assess brain atrophy patterns associated with different FTD clinical phenotypes. Studies show that volumetric MRI allows differentiation of atrophy patterns when analyzed at a group level but currently does not allow assessment on an individual patient level [44]. Several other advanced MRI techniques provide additional information about brain microstructure, and their role in diagnosis of FTD is being investigated [44]. Zhang et al [49] demonstrated that diffusion tensor imaging has significantly greater accuracy for classifying subtypes of FTD than volumetric brain MRI. The role of arterial spin labeling MRI in FTD is currently being studied. The patterns detected using arterial spin labeling MRI has been shown to be similar to FDG-PET findings, and this technique potentially could represent a future alternative to FDG-PET [44].


Dementia

Dementia. HMPAO SPECT or SPECT/CT Brain Tc-99m HMPAO SPECT has been found to be useful in distinguishing FTD from AD and VaD with a pattern of bilateral anterior hypoperfusion. Tc-99m HMPAO SPECT may be used as an adjunct to clinical evaluation and CT but it is not a first-line test [50]. Variant 3: Suspected dementia with Lewy bodies. Initial imaging. Dementia with Lewy bodies (DLB) has been recognized as the second most prevalent neurodegenerative dementia in the elderly, causing up to 15% of cases [51]. It is a synucleinopathy with accumulation of insoluble alpha- Synuclein that aggregates to form Lewy bodies, which are the major pathological feature of the disease. To increase the accuracy of diagnosis of DLB, the latest diagnostic criteria incorporate findings from neuroimaging such as CT, MRI, SPECT, and PET [52]. Some authors have suggested a multimodality approach combining MRI and SPECT modalities as a useful and practical approach for differentiating DLB from AD [51]. CT Head Noncontrast CT head is a good first-line examination to exclude mimics like brain tumor or subdural hematoma. Relative preservation of the medial temporal lobe structures is also a supportive imaging biomarker according to the fourth consensus report of the DLB consortium [52]. CT with IV contrast or dual-phase CT imaging is not needed for initial evaluation. Dementia Amyloid PET/CT Brain DLB is also accompanied by amyloid deposition like AD, but overall, there is decreased uptake compared when with AD patients on amyloid imaging. Compared to Parkinson disease, DLB patients show a higher level of amyloid deposition [53]. At this time, amyloid PET/CT has very limited usefulness for diagnosis of DLB. Ioflupane SPECT or SPECT/CT Brain In the present guidelines, decreased dopamine transporter uptake is of the greatest importance among various neuroimaging findings and is listed as one of the suggestive features.


Dementia

Dementia. Functional imaging of the dopamine transporter (I-123 Ioflupane) using SPECT might identify a defect in the nigrostriatal pathway that occurs in a variety of disorders including DLB and Parkinson disease. I-123 Ioflupane striatal activity tends to be normal in AD and low in DLB and Parkinson disease; however, AD and DLB can coexist in the same patient, potentially confounding results [11,51]. This is not a first-line imaging test but may be valuable after cross-sectional imaging to exclude other pathology. MR Spectroscopy Head There is sparse MR spectroscopy data on DLB. In one study [55], DLB patients were characterized by decreased NAA/Cr in the occipital voxel. AD patients were characterized by lower NAA/Cr in the frontal and posterior cingulate voxels. Normal NAA/Cr levels in the frontal voxel differentiated DLB patients with preserved hippocampal volumes from AD patients. MR spectroscopy abnormalities associated with loss of neuronal integrity localized to the occipital lobes in DLB, and the posterior cingulate gyri and frontal lobes in AD. The pattern of MR spectroscopy abnormalities may have a role in differential diagnosis of DLB and in distinguishing DLB patients with overlapping AD pathology. Although in the future, MR spectroscopy can provide additional useful information in the ante-mortem diagnosis of DLB; at present, its usefulness is limited. MRI functional (fMRI) Head Studies with fMRI show reduced activation of the occipital-temporal lobe regions during visual tasks. Resting state fMRI has demonstrated increased functional connectivity between the right posterior cingulate gyrus and other regions of the brain and reduced cortico-cortical connectivity. However, the diagnostic utility of fMRI for diagnosis of DLB has not been validated, and thus it cannot be recommended [56]. MRI Head Routine MRI head is performed to exclude other lesions like tumor or subdural hematoma. Contrast-enhanced MRI is not needed for initial evaluation.


Dementia

Dementia. Volumetric MRI can be done as a secondary test to support the diagnosis. On structural MRI, patients with DLB show less atrophy of the hippocampus and other medial temporal lobe structures compared with AD. For similar levels of dementia severity, DLB appears to have greater subcortical structure atrophy (thalamus, caudate, amygdala, ventral diencephalon, substantia nigra, and midbrain) compared with AD [57]. However, on a single subject level, structural changes are not helpful in differentiating DLB from other dementias. Diffusion tensor imaging studies have described the potential importance of the precuneus in the pathogenesis of DLB as well as AD [35]. HMPAO SPECT or SPECT/CT Brain The most important finding on brain-perfusion SPECT in DLB is occipital hypoperfusion. This hypoperfusion is listed as a supportive feature in the consensus guidelines [52], and this can be a second-line imaging test to help with the diagnosis. However, this test is less commonly used in clinical practice and has been largely replaced by other imaging modalities. Variant 4: Suspected vascular dementia. Initial imaging. Cerebral vascular disease, especially common in the elderly, can lead to VaD [11]. The diagnosis of VaD involves the presence of significant cerebrovascular pathology or risk factors, assessed clinically or using neuroimaging. Recently, the concept of vascular cognitive impairment has been invoked, which refers to the whole spectrum of Dementia disorders in which there is cognitive impairment and either clinical evidence of previous stroke or imaging evidence of vascular brain injury, either in isolation (pure vascular disease) or in association with other pathologies (mixed disease) [58]. The three main causes of vascular cognitive impairment are large vessel strokes (macroangiopathy, arteriosclerosis), small vessel disease (microangiopathy, arteriolosclerosis), and microhemorrhages. Structural neuroimaging has been incorporated as an important element of the diagnosis of VaD [59].


Dementia

Dementia. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy is an autosomal- dominant hereditary small-artery vasculopathy caused by mutations in the notch3 gene on chromosome 19. Clinically, the disease is characterized by migraine with aura, strokes and progressive subcortical dementia, and mood disturbances. MRI in these patients shows focal lacunar infarcts and leukoaraiosis. Lesion load increases with age. Besides familial anamnesis and clinical history, structural MRI changes in these patients help to suggest the diagnosis by showing characteristic hyperintense T2 or fluid-attenuated inversion recovery lesions, which predominate in the frontal, parietal, and anterior temporal cortexes and in the external capsule [60]. Diagnosis is confirmed by skin biopsy or detection of a pathogenic notch3 mutation on direct sequencing. CT Head Most acute stroke patients undergo brain imaging by unenhanced CT head to evaluate for size, territory, and acuity of infarct to exclude hemorrhage and evaluate for stroke mimics (such as brain tumors). Furthermore, the presence and severity of white matter changes and brain atrophy can also be readily determined from CT head imaging. CT head with IV contrast is not needed to evaluate VaD. CTA Head CT angiography (CTA) is a sensitive modality and may be used as an alternative to MR angiography (MRA) to detect vascular occlusion or stenosis intracranially. However, vascular imaging is not needed to make a diagnosis of VaD; rather, the diagnosis relies on clinical criteria and evidence of end organ damage in the brain. FDG-PET/CT Brain FDG-PET/CT in VaD can show multiple focal cortical and subcortical metabolic defects, a pattern different from AD and may be useful in differentiating the two entities in the demented patient [61]; however, it is not a first-line imaging test. MR Spectroscopy Head MR spectroscopy shows injury to the axons by measuring the levels of NAA and Cr [62,63].


Dementia

Dementia. MR spectroscopy is a research tool and, to date, does not appear to clinically help establish a diagnosis of VaD or mixed VaD and AD. MRA Head Although vascular imaging is not needed for diagnosis of suspected VaD, MRA is a sensitive modality to detect vascular occlusion or stenosis intracranially. MRA Neck Vascular imaging is not needed for workup of suspected VaD. MRI functional (fMRI) Head The use of fMRI is investigational and, to date, does not appear to clinically help establish a diagnosis of VaD or mixed VaD and AD. MRI Head One of the roles of neuroimaging is to document the presence or absence of strokes. Although CT can detect the presence or absence of infarctions in patients with dementia, histopathologically verified cases of VaD with normal CT studies have been reported [28]. Thus, MRI is preferable to CT for detecting vascular lesions in patients with dementia. On MRI, evidence for vascular abnormalities includes cortical or subcortical infarcts, leukoariosis or white matter T2 hyperintensity, microhemorrhages, and lacunar infarct. Hippocampal atrophy has been seen in patients with vascular cognitive impairment [64], and some studies have argued that it is the best predictor of post stroke dementia [65]. The above-mentioned imaging findings on routine MRI lack specificity and correlation with degree of cognitive impairment. Diffusion tensor imaging has been shown to correlate better with cognitive deficits, but its use has been confined to research settings [66]. Differentiation of VaD from either AD with superimposed cerebrovascular disease or mixed AD and VaD is especially difficult and is best performed by amyloid PET/CT brain. On MRI, extensive infarctions (cortical or Dementia lacunar or both) and white-matter changes (hyperintense on T2-weighted MRI) in a patient with dementia favor a contribution from VaD or mixed VaD and AD over AD. The absence or mild extent of these changes in a patient with dementia argues against a diagnosis of VaD.


Dementia

Dementia. The abovementioned findings are optimally visualized on noncontrast MRI; IV contrast is not needed. US Duplex Doppler Carotid Artery Atherosclerotic burden, as defined by carotid ultrasound (US), is associated with worse cognitive performance and subsequent cognitive decline [67]. However, US duplex Doppler is not needed to diagnose VaD. Variant 5: Suspected idiopathic normal-pressure hydrocephalus. Initial imaging. Normal-pressure hydrocephalus (NPH) is characterized by the clinical triad of dementia, gait disturbance, and urinary incontinence. Other diagnostic features include normal CSF pressure at lumbar puncture, communicating hydrocephalus documented on MRI or CT, and ventricular influx but no passage of isotope over the convexities on radionuclide DTPA cisternography. The Guideline Development, Dissemination, and Implementation Subcommittee of the AAN has concluded that shunting is possibly effective in idiopathic NPH (INPH) [68]. Several clinical, laboratory, and imaging signs can improve distinction between responders and nonresponders to shunting. However, there is no test or combination of clinical findings and tests that accurately predicts response to shunting. Clinical features that favor shunt responsiveness include predominance of gait disturbance, mild to moderate degree of dementia, and rapid clinical progression of urinary incontinence. Imaging features of responders versus nonresponders are discussed below. CT Head CT head without IV contrast is an appropriate first-line imaging test to evaluate for ventriculomegaly out of proportion to sulci and to exclude other pathologies. It can also show transependymal CSF flow. CT head with IV contrast is not indicated for initial evaluation of NPH. MR Spectroscopy Head MR spectroscopy is not useful in differentiating INPH from other types of dementia nor does it help in patient selection for ventriculoperitoneal shunting [69].