Antineutrophil Cytoplasmic Antibodies

Antineutrophil cytoplasmic antibodies (ANCA) are detected on peripheral blood neutrophils by indirect immunofluorescence (IIF) techniques. Two major staining patterns have been described. A cytoplasmic (c-ANCA) staining pattern characterized by diffuse granularity of the cytoplasm is classically seen in patients with Wegener granulomatosis. These c-ANCA antibodies typically recognize proteinase-3 on enzyme-linked immunosorbent assay (ELISA) testing. By contrast, a thin homogeneous rim-like staining of the perinuclear cytoplasm (p-ANCA) is associated with microscopic polyangiitis and antibodies directed against myeloperoxidase. A third pattern exists, often referred to as atypical p-ANCA, that appears as a broad heterogeneous staining of the nuclear periphery, often with intranuclear inclusions to suggest that the antigen may be in the periphery of the nucleus rather than in the perinuclear cytoplasm. This atypical p-ANCA is associated with IBD and primary sclerosing cholangitis and autoimmune hepatitis type I. Atypical p-ANCA is present in 40% to 80% of patients with UC and 5% to 25% of patients with Crohn disease. The target antigens of atypical p-ANCA have not been identified, but several have been explored, including cathepsin G, elastase, β-glucuronidase, lactoferrin, and the natural antibiotic bactericidal permeability increasing protein. Myeloperoxidase and proteinase-3, the antigens recognized by typical p-ANCA and c-ANCA, respectively, are not autoantigens in IBD. Because the target antigens of atypical p-ANCA have not been identified, there is no ELISA test to distinguish these antibodies from typical p-ANCA. Rather one must rely on IIF, which has drawbacks, including differences in methodology and subjective interpretation of staining pattern that result in substantial variability of results among laboratories. Consequently, the numerous studies describing the performance characteristics of atypical p-ANCA in the detection of IBD have yielded heterogeneous and discrepant results. Given this variability, an alternative methodology was developed by Targan and colleagues to distinguish atypical p-ANCA from the typical vasculitis-associated p-ANCA by a 3-step process that involves IIF staining before and after treatment of neutrophils with deoxyribonuclease (DNase). Addition of DNase abolishes the fluorescent staining of atypical, UC-associated p-ANCA, allowing distinction from the typical p-ANCA pattern. In a large meta-analysis, the overall sensitivity of atypical p-ANCA for detecting UC was 55%, with a specificity of 89%, a positive likelihood ratio of 4.5, and a negative likelihood ratio of −0.5.

Anti- Saccharomyces Cerevisiae Antibodies

Anti- Saccharomyces cerevisiae antibodies (ASCAs) are antibodies directed against a cell wall component of the baker’s and brewer’s yeast S cerevisiae . This antigen is not unique to the cell wall of S cerevisiae , however. Recently it has been discovered that Candida albicans is an immunogen for ASCAs. ASCAs are present in 50% to 60% of patients with Crohn disease, 10% to 15% of those with UC, 20% of healthy first-degree relatives of patients with Crohn disease, and 0% to 5% of healthy controls. IgG and IgA antibodies are produced, and the specificity for Crohn disease increases if both antibodies are positive. As with atypical p-ANCA, there is substantial heterogeneity of ASCA results among laboratories, attributable to a lack of standardization of the assay methodology and defined cutoff values.

Newer Serologic Biomarkers

Anti-OmpC antibody is an IgA antibody directed against the outer membrane porin C protein of Escherichia coli and is present in 55% of patients with Crohn disease but only in 5% to 11% of patients with UC and in 5% of healthy controls. In the pediatric population with Crohn disease, however, the prevalence of anti-OmpC antibodies is markedly reduced. Anti-OmpC antibodies are present in 5% to 15% of patients with Crohn disease who are ASCA negative, and they can help to identify a subset of patients that would otherwise be missed by conventional serologic testing.

Antibodies to I2, a bacterial sequence derived from Pseudomonas fluorescens , are associated with Crohn disease. Anti-I2 IgA antibodies are present in 30% to 50% of patients with Crohn disease, 10% of patients with UC, 19% of patients with other inflammatory conditions of the intestine, and 5% of healthy controls. The sensitivity and specificity of I2 antibodies for detecting Crohn disease are 42% and 76%, respectively. The low sensitivity and modest specificity limit the clinical utility of this antimicrobial marker.

Antipancreatic antibodies (PAB) are more common in Crohn disease (30%) than in UC (2%–6%) or healthy subjects (0%–2%). PAB antibodies are directed against an unidentified antigen on exocrine pancreatic tissue. Their utility in IBD diagnosis and management remains to be demonstrated.

CBir1 flagellin is a dominant antigen of the enteric microbial flora that induces an immune response in colitic mice. Approximately half of Crohn patients have anti-CBir1 antibodies compared with only 6% of patients with UC and 8% of control subjects. The presence of anti-CBir1 antibodies is independent of the presence of other antimicrobial or autoantigens in IBD patients. Among the subset of Crohn patients who are positive only for p-ANCA, 40% to 44% express anti-CBir1 antibodies compared with only 4% of p-ANCA–positive UC patients.

There has been increasing interest in exploring antibodies to carbohydrate (glycan)-based antigens because mucosal immune responses involve interaction with the glycosylated cell wall components of luminal fungi, yeast, and bacteria. Three novel antiglycan antibodies have been described in IBD patients. Antilaminaribioside carbohydrate IgG antibodies (ALCA), antichitobioside carbohydrate IgA antibodies (ACCA), and antimannobioside carbohydrate IgA antibodies (AMCA) are all associated with Crohn disease and are present in 44% to 50% of ASCA-negative patients. Although highly specific for Crohn disease, these carbohydrate antibodies demonstrate lackluster sensitivity (18%–28%) for distinguishing Crohn disease from UC. In a Hungarian cohort of patients, these antiglycan antibodies were shown to be associated with the NOD2/CARD15 genotype in Crohn disease. Seow and colleagues demonstrated that antichitin IgA (anti-C) and antilaminarin IgA (anti-L) antibodies improve differentiation of Crohn disease from UC and are independently associated with complicated Crohn disease. These latter anticarbohydrate antibodies are related to, but distinct from, ALCA and ACCA.

Applications of Serologic Biomarkers

C-Reactive Protein

C-reactive protein (CRP) is an acute phase protein, produced by hepatocytes under the stimulation of interleukin-6, interleukin-1β, and tumor necrosis factor-α and is well known as a marker of systemic inflammation. The rapid production of CRP in response to an acute-phase stimulus within hours and its short half-life make it well suited as a marker for monitoring of disease activity in IBD. However, CRP upregulation is not specific to IBD, and occurs in response to other inflammatory diseases, infectious stimuli, tissue necrosis, malignancy, and other conditions. Some patients have polymorphisms in the CRP gene that result in lower CRP levels, rendering CRP an unreliable measure of inflammatory activity in those patients.

CRP is elevated in 70% to 100% of patients with Crohn disease and 50% to 60% of patients with UC, and the level correlates with disease severity such that mean CRP concentration is higher in patients with severe Crohn disease than those with moderate disease and is even lower in patients with mild disease. The same trend is evident for UC, but the absolute levels of CRP are much lower than in Crohn disease. A study from the Mayo Clinic demonstrated a correlation between CRP levels and evidence of inflammation as assessed by endoscopy and histology in patients with Crohn disease. Among the patients with UC, elevated CRP was associated with clinical disease activity and endoscopic severity, but not histologic degree of inflammation.

CRP may also be useful in prognosticating disease course. A prospective study followed 71 patients with Crohn disease in remission with serial measurements of CRP and other biomarkers every 6 weeks. Elevated CRP (>20 mg/L) forecasted clinical disease exacerbation within 6 weeks. In the setting of severe UC requiring parenteral steroids, a high CRP level has been demonstrated in several predictive models to portend a poor prognosis and higher rate of colectomy. A population-based study from Norway showed that elevated CRP at diagnosis predicted nearly a fivefold increase in the odds of subsequent surgery among patients with UC. A similar association between CRP level at diagnosis and surgery was demonstrated for patients with Crohn ileitis.

Although CRP has been used for decades, it has received increased attention lately due to the finding in randomized controlled studies that elevated CRP levels are associated with lower placebo response and consequently increased treatment effect. This may be explained by the observation that CRP can aid in the distinction between inflammatory and irritable bowel symptoms, the latter being more likely to exhibit improvement with placebo. Other authors have confirmed the ability of CRP to predict treatment response. Louis and colleagues demonstrated that an elevated CRP level (>5 mg/mL) is associated with a favorable response to infliximab. However, in using CRP as an inclusion criterion or stratification in clinical trials, one must remember that some patients with active IBD may not produce CRP and therefore will be excluded in those studies.

Summary and Recommendations

Serologic biomarkers represent a novel and exciting tool for evaluation of IBD, but currently they have limited clinical application. Insufficient sensitivity and specificity of these antibodies renders them unreliable for establishing the diagnosis of IBD, particularly in patients with a low pretest probability of disease. Likewise, their use in clarifying disease diagnosis among patients with IBDU is hampered by the observation that patients with Crohn disease with isolated colonic involvement have a serologic profile similar to UC. Consequently, serologic panels cannot be routinely recommended for diagnosing IBD or distinguishing between Crohn disease and UC. The potential for serologic biomarkers to predict disease onset or behavior is intriguing, and prospective studies are underway to assess whether these markers also predict response to therapies and warrant a different treatment approach that results in changed short- and long-term outcomes. However, there is insufficient evidence that serologic profiles should override careful clinical evaluation in determining therapeutic management decisions.

CRP is a helpful adjunct tool in evaluating patients with IBD. Although the lack of specificity of CRP limits its utility for initial diagnosis, CRP can be valuable for assessing disease relapse in patients with established IBD and who have demonstrated an elevated CRP at the time of clearly active disease. Thereafter, use of CRP to confirm or predict relapse is helpful. Whether it warrants an immediate change in therapy has not been prospectively studied, but it certainly can assist in the assessment of adherence with current therapy and discussions with the patient.

CT

Cross-sectional imaging with CT offers several distinct advantages over conventional small bowel radiography. Multiplanar imaging allows clear delineation of superimposed bowel loops, and visualization of extraintestinal structures permits identification of disease complications, such as abscesses, fistulae, or phlegmonous changes. Traditional CT evaluation of the abdomen uses a positive contrast agent such as iodine or barium that highlights intraluminal filling defects such as polyps or masses. By comparison, CT enterography (CTE) uses the combination of neutral (low-density) oral contrast and intravenous (IV) contrast to provide optimal distinction between the enhancing small intestinal wall and the adjacent low-attenuation intestinal lumen. This technique facilitates evaluation of the bowel wall and mucosa. Bowel distention is typically achieved with a low-concentration barium solution mixed with sorbitol and water. The amount and timing of oral contrast ingestion has not been standardized, but volumes of 900 to 1800 mL have been described.

CT enteroclysis involves placement of a nasojejunal tube and rapid infusion of enteric contrast directly into the proximal small bowel. This technique improves bowel distention, but it is time consuming and uncomfortable for patients, and the incremental yield of this approach over CTE is modest at best. Findings on CTE or CT enteroclysis that indicate active inflammation include segmental mural enhancement, wall thickening, and mural stratification. Likewise, fibrofatty proliferation, engorgement of the vasa recta (sometimes called a “comb sign”), and reactive mesenteric adenopathy are extraluminal findings that support a diagnosis of active inflammation. Luminal narrowing, if present, can be because of inflammation with edema or chronic fibrostenotic disease, and the distinction between these 2 conditions is not always possible with CT.

In a prospective study of 96 patients undergoing both ileoscopy and CTE, the findings of mural enhancement and wall thickness were able to detect active Crohn disease, with a sensitivity of 80% to 90%. CTE and ileoscopy were equally accurate at predicting histologic inflammation, and radiologic findings correlated with clinical disease activity. In comparison with conventional fluoroscopic imaging, at least 2 studies have found that CTE is more sensitive than SBFT for detecting active disease. Studies that compared CTE with capsule endoscopy report varying results, attributable in part to differences in study design. A prospective study comparing multiple small bowel imaging modalities described a sensitivity of 53% for CTE compared with capsule endoscopy (71%), ileoscopy (65%), and SBFT (24%). This study defined any positive small bowel finding consistent with Crohn disease as a true positive and calculated the diagnostic yield of each modality. This methodology does not allow calculation of specificity because each finding is by definition a true positive. A similar analysis by Solem and colleagues prospectively compared CTE with capsule endoscopy, ileoscopy, and SBFT, using a consensus clinical diagnosis of Crohn disease as the reference standard. This study demonstrated equivalent sensitivities for CTE and capsule endoscopy (83%), but CTE was far more specific (89% vs 53%). The authors suggested an algorithm involving these modalities, in which ileocolonoscopy and biopsy is the first test, followed by CTE and, if necessary and if there are no obstructive symptoms or findings, capsule endoscopy.

CTE and CT enteroclysis offer several distinct advantages over conventional fluoroscopic barium studies. SBFT is prone to obscuration of findings because of superimposed bowel loops, but this can be overcome using multiplanar images on CT. In addition, CT can better detect extraintestinal processes that may be missed with SBFT or with endoscopic imaging. When compared with capsule endoscopy, CTE is similarly or slightly less sensitive but far more specific.

The benefits of CTE, however, must be weighed against the deleterious effects of cumulative ionizing radiation, particularly in patients who are young or pregnant. A recent study drew attention to the alarming dose of radiation exposure that many patients with Crohn disease receive. This radiation exposure was primarily attributable to the increased use of CT imaging. Factors associated with exposure to high levels of ionizing radiation included penetrating disease, upper gastrointestinal tract involvement, diagnosis at an early age, requirement for steroids or infliximab, and multiple surgeries.

MRI

Concerns about diagnostic radiation exposure with CT have fueled interest in developing alternative imaging modalities that avoid this risk. Historically, MRI of the bowel was hampered by long image acquisition times resulting in respiratory and peristaltic motion artifact that compromised image quality. However, technologic advances in image acquisition combined with administration of bowel relaxant medication during the procedure have led to substantial improvements in the quality of MR images of the intestine. Administration of large-volume oral contrast results in luminal distention, facilitating evaluation of bowel wall thickness and regularity. MR enteroclysis can also be performed by distending the small intestine with enteric contrast administered through a nasojejunal tube. Analogous to CT or conventional enteroclysis, MR enteroclysis results in superior distention of the bowel but at the sacrifice of patient comfort, and the increased distention may not be necessary in many cases. A prospective study of patients randomized to MR enterography or MR enteroclysis showed identical sensitivity (88%) in both groups.

Superior image quality requires adequate bowel distention with oral contrast, minimization of motion artifact with ultrafast sequences and bowel relaxants, and enhanced bowel wall visualization with IV contrast. Several enteric contrast agents have been investigated for MR enterography. Most studies in Crohn disease use biphasic contrast agents that demonstrate low signal intensity on T1-weighted images, allowing clear delineation of the dark lumen from the hyperenhancing inflammatory segments of the bowel wall after IV contrast. Large volumes of water or even milk have been used effectively, but these liquids can be rapidly absorbed, resulting in suboptimal distention of the distal bowel. Other centers have reported better success with osmotic and/or bulking agents that retain water in the lumen, including mannitol, sorbitol, and locust bean gum. Reduction of peristalsis with IV administration of hyoscine butylbromide (Buscopan) or glucagon is integral to preventing motion artifact and preserving image quality. Multiple pulse sequences and multiphasic acquisitions are obtained, and each provides complementary information. Typical MRI findings that indicate active inflammatory disease include mural thickening; ulcerations; hyperenhancement; increased mesenteric vascularity (the “comb sign”); mesenteric inflammation; reactive adenopathy; and complications such as obstruction, perforation, or abscess.

Several investigators have reported that MRI is more sensitive than conventional fluoroscopic barium studies for detecting transmural bowel inflammation and has a sensitivity of as high as 96%. However, mild mucosal changes are better visualized with traditional small bowel series radiographs. The multiphasic sequences obtained with MRI can be useful to distinguish inflammatory from fibrostenotic strictures by detecting the differential water content of edematous tissue. Diffusion-weighted imaging has also been shown to be a feasible technique for the detection of inflammation in Crohn disease. When compared with endoscopy, MR enterography demonstrates a sensitivity of 84% to 96% and a specificity of 92% to 100% for detection of IBD. In a prospective comparison of MR enterography and CTE, the sensitivities were similar for detecting active Crohn disease (91% vs 95%, respectively).

MRI can also provide detailed and anatomically important information about perianal fistulae, which guides operative management, and it has therefore become a dominant imaging modality for assessment and staging of perianal complications in Crohn disease. Although MR colonography has been investigated, its role in IBD diagnosis and management remains undetermined, but it may potentially be of use in patients with Crohn colitis or UC in whom optical colonoscopy is incomplete, contraindicated, or declined by the patient.

MR enterography is a safe and accurate method of evaluating the small bowel and extraluminal structures in patients with Crohn disease. The advantages of this technique over CT include a lack of ionizing radiation, greater safety in renal insufficiency and in pregnancy, and superior evaluation of the pelvic soft tissues and perianal fistulae. The downside of MRI includes a lack of appropriately trained radiologists outside of specialized centers and a considerable cost to perform the examination. Some authors have proposed in a cost-utility analysis that MR imaging may be superior to SBFTbecause of improved diagnostic accuracy that outweighs the increased cost. This assertion remains to be substantiated with prospective data ( Figs. 1 and 2 ).

Ileal stricture seen on magnetic resonance enterography, coronal view.

Ileal inflammation seen on magnetic resonance enterography, axial view.

Ultrasound

Abdominal ultrasound is an evolving imaging modality with a variety of potential applications in patients with established or suspected IBD. There has been renewed interest in exploring ultrasound as a tool in IBD because of its lower cost, excellent safety profile, and ability to be used in pregnant patients. Improvements in ultrasound equipment allow high-resolution images with improved depth of penetration, permitting detailed visualization of the bowel wall and adjacent mesenteric structures.

Inflammation is identified by increased bowel wall diameter, alteration of the normal sonographic pattern of mural stratification, and increased blood flow as assessed by Doppler evaluation. In a meta-analysis, the sensitivity of ultrasound for the initial diagnosis of Crohn disease ranges from 75% to 94%, with a specificity of 67% to 100%, depending on the cutoff value for defining mural thickening. Ultrasound is most sensitive for detecting disease of the ileum (95%), with decreased sensitivity for detecting disease in the left colon (88%), transverse colon (82%), or jejunum (72%). Ultrasound can accurately identify bowel wall thickening and can distinguish fibrosis from acute edema. In a thickened bowel segment, loss of mural stratification is associated with inflammation, whereas retained stratification suggests fibrosis. Introduction of a new microbubble contrast agent that persists in the bloodstream for several minutes has facilitated development of contrast-enhanced ultrasound (CE-US) for imaging parenchymal organs. By evaluating the presence and distribution of blood flow within the bowel wall, CE-US can assess disease activity with high sensitivity (93%) and specificity (93%) and has a strong correlation with clinical disease activity indices.

Some challenges remain, however, that limit widespread application of abdominal ultrasound. Although ultrasound findings are sensitive for the bowel loop being examined, intraluminal gas can obscure visualization of some bowel loops altogether, and obese patients can be challenging to evaluate because of poor depth of penetration. Furthermore, an experienced operator and equipment with enhanced resolution are essential to obtaining high-quality images, and expertise in abdominal ultrasound is not pervasive. Nonetheless, these intriguing data suggest a developing role for ultrasound imaging in patients with IBD that warrants continued investigation.

Positron Emission Tomography

Positron emission tomography (PET) scanning is a nuclear medicine technique that uses [ ¹⁸ F] fluoro-2-deoxy- d -glucose to identify areas of increased metabolic activity, and it has been used to evaluate multiple infectious, inflammatory, and malignant diseases. Several authors have demonstrated in prospective studies that PET, alone or in combination with CT, can successfully identify active inflammation in both children and adults with established or suspected IBD. A study by Meisner and colleagues reported that PET alone was sufficient to detect inflammation in UC, whereas PET/CT was more useful in Crohn disease. Although data are quite limited, PET appears to have excellent sensitivity and may even be able to detect subclinical inflammation in patients with UC. However, questions remain about its specificity, and the practical application of PET in IBD management has not been established.

Summary and Recommendations

Novel imaging techniques represent a valuable noninvasive alternative to endoscopy for evaluation of the small bowel. CTE is preferable to SBFT as the initial radiologic imaging study in patients with ileal Crohn disease because of the capacity for multiplanar imaging and the ability to detect mural thickening and extraluminal findings. In addition, the utility of SBFT is declining, as the latest generation of radiologists has less experience with conventional barium techniques and interpretation. As the technology and experience with MR enterography imaging improves, MRE is favored over CTE not only due to the ability to distinguish active inflammation from fibrosis but also due to the avoidance of ionizing radiation. This is especially true for the evaluation of perianal Crohn disease, where MRI is clearly superior to other radiologic techniques. Abdominal ultrasound is an attractive and cost-effective option, but it remains substantially limiting by the absence of experience. PET scanning, although intriguing, remains investigational for the evaluation of patients with IBD.

CT

Cross-sectional imaging with CT offers several distinct advantages over conventional small bowel radiography. Multiplanar imaging allows clear delineation of superimposed bowel loops, and visualization of extraintestinal structures permits identification of disease complications, such as abscesses, fistulae, or phlegmonous changes. Traditional CT evaluation of the abdomen uses a positive contrast agent such as iodine or barium that highlights intraluminal filling defects such as polyps or masses. By comparison, CT enterography (CTE) uses the combination of neutral (low-density) oral contrast and intravenous (IV) contrast to provide optimal distinction between the enhancing small intestinal wall and the adjacent low-attenuation intestinal lumen. This technique facilitates evaluation of the bowel wall and mucosa. Bowel distention is typically achieved with a low-concentration barium solution mixed with sorbitol and water. The amount and timing of oral contrast ingestion has not been standardized, but volumes of 900 to 1800 mL have been described.

CT enteroclysis involves placement of a nasojejunal tube and rapid infusion of enteric contrast directly into the proximal small bowel. This technique improves bowel distention, but it is time consuming and uncomfortable for patients, and the incremental yield of this approach over CTE is modest at best. Findings on CTE or CT enteroclysis that indicate active inflammation include segmental mural enhancement, wall thickening, and mural stratification. Likewise, fibrofatty proliferation, engorgement of the vasa recta (sometimes called a “comb sign”), and reactive mesenteric adenopathy are extraluminal findings that support a diagnosis of active inflammation. Luminal narrowing, if present, can be because of inflammation with edema or chronic fibrostenotic disease, and the distinction between these 2 conditions is not always possible with CT.

In a prospective study of 96 patients undergoing both ileoscopy and CTE, the findings of mural enhancement and wall thickness were able to detect active Crohn disease, with a sensitivity of 80% to 90%. CTE and ileoscopy were equally accurate at predicting histologic inflammation, and radiologic findings correlated with clinical disease activity. In comparison with conventional fluoroscopic imaging, at least 2 studies have found that CTE is more sensitive than SBFT for detecting active disease. Studies that compared CTE with capsule endoscopy report varying results, attributable in part to differences in study design. A prospective study comparing multiple small bowel imaging modalities described a sensitivity of 53% for CTE compared with capsule endoscopy (71%), ileoscopy (65%), and SBFT (24%). This study defined any positive small bowel finding consistent with Crohn disease as a true positive and calculated the diagnostic yield of each modality. This methodology does not allow calculation of specificity because each finding is by definition a true positive. A similar analysis by Solem and colleagues prospectively compared CTE with capsule endoscopy, ileoscopy, and SBFT, using a consensus clinical diagnosis of Crohn disease as the reference standard. This study demonstrated equivalent sensitivities for CTE and capsule endoscopy (83%), but CTE was far more specific (89% vs 53%). The authors suggested an algorithm involving these modalities, in which ileocolonoscopy and biopsy is the first test, followed by CTE and, if necessary and if there are no obstructive symptoms or findings, capsule endoscopy.

CTE and CT enteroclysis offer several distinct advantages over conventional fluoroscopic barium studies. SBFT is prone to obscuration of findings because of superimposed bowel loops, but this can be overcome using multiplanar images on CT. In addition, CT can better detect extraintestinal processes that may be missed with SBFT or with endoscopic imaging. When compared with capsule endoscopy, CTE is similarly or slightly less sensitive but far more specific.

The benefits of CTE, however, must be weighed against the deleterious effects of cumulative ionizing radiation, particularly in patients who are young or pregnant. A recent study drew attention to the alarming dose of radiation exposure that many patients with Crohn disease receive. This radiation exposure was primarily attributable to the increased use of CT imaging. Factors associated with exposure to high levels of ionizing radiation included penetrating disease, upper gastrointestinal tract involvement, diagnosis at an early age, requirement for steroids or infliximab, and multiple surgeries.

MRI

Concerns about diagnostic radiation exposure with CT have fueled interest in developing alternative imaging modalities that avoid this risk. Historically, MRI of the bowel was hampered by long image acquisition times resulting in respiratory and peristaltic motion artifact that compromised image quality. However, technologic advances in image acquisition combined with administration of bowel relaxant medication during the procedure have led to substantial improvements in the quality of MR images of the intestine. Administration of large-volume oral contrast results in luminal distention, facilitating evaluation of bowel wall thickness and regularity. MR enteroclysis can also be performed by distending the small intestine with enteric contrast administered through a nasojejunal tube. Analogous to CT or conventional enteroclysis, MR enteroclysis results in superior distention of the bowel but at the sacrifice of patient comfort, and the increased distention may not be necessary in many cases. A prospective study of patients randomized to MR enterography or MR enteroclysis showed identical sensitivity (88%) in both groups.

Superior image quality requires adequate bowel distention with oral contrast, minimization of motion artifact with ultrafast sequences and bowel relaxants, and enhanced bowel wall visualization with IV contrast. Several enteric contrast agents have been investigated for MR enterography. Most studies in Crohn disease use biphasic contrast agents that demonstrate low signal intensity on T1-weighted images, allowing clear delineation of the dark lumen from the hyperenhancing inflammatory segments of the bowel wall after IV contrast. Large volumes of water or even milk have been used effectively, but these liquids can be rapidly absorbed, resulting in suboptimal distention of the distal bowel. Other centers have reported better success with osmotic and/or bulking agents that retain water in the lumen, including mannitol, sorbitol, and locust bean gum. Reduction of peristalsis with IV administration of hyoscine butylbromide (Buscopan) or glucagon is integral to preventing motion artifact and preserving image quality. Multiple pulse sequences and multiphasic acquisitions are obtained, and each provides complementary information. Typical MRI findings that indicate active inflammatory disease include mural thickening; ulcerations; hyperenhancement; increased mesenteric vascularity (the “comb sign”); mesenteric inflammation; reactive adenopathy; and complications such as obstruction, perforation, or abscess.

Several investigators have reported that MRI is more sensitive than conventional fluoroscopic barium studies for detecting transmural bowel inflammation and has a sensitivity of as high as 96%. However, mild mucosal changes are better visualized with traditional small bowel series radiographs. The multiphasic sequences obtained with MRI can be useful to distinguish inflammatory from fibrostenotic strictures by detecting the differential water content of edematous tissue. Diffusion-weighted imaging has also been shown to be a feasible technique for the detection of inflammation in Crohn disease. When compared with endoscopy, MR enterography demonstrates a sensitivity of 84% to 96% and a specificity of 92% to 100% for detection of IBD. In a prospective comparison of MR enterography and CTE, the sensitivities were similar for detecting active Crohn disease (91% vs 95%, respectively).

MRI can also provide detailed and anatomically important information about perianal fistulae, which guides operative management, and it has therefore become a dominant imaging modality for assessment and staging of perianal complications in Crohn disease. Although MR colonography has been investigated, its role in IBD diagnosis and management remains undetermined, but it may potentially be of use in patients with Crohn colitis or UC in whom optical colonoscopy is incomplete, contraindicated, or declined by the patient.

MR enterography is a safe and accurate method of evaluating the small bowel and extraluminal structures in patients with Crohn disease. The advantages of this technique over CT include a lack of ionizing radiation, greater safety in renal insufficiency and in pregnancy, and superior evaluation of the pelvic soft tissues and perianal fistulae. The downside of MRI includes a lack of appropriately trained radiologists outside of specialized centers and a considerable cost to perform the examination. Some authors have proposed in a cost-utility analysis that MR imaging may be superior to SBFTbecause of improved diagnostic accuracy that outweighs the increased cost. This assertion remains to be substantiated with prospective data ( Figs. 1 and 2 ).

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