Advances in Use of Endoscopy, Radiology, and Biomarkers to Monitor Inflammatory Bowel Diseases

Crohn's disease and ulcerative colitis are heterogeneous inflammatory bowel diseases, and therapeutic requirements vary among patients. We have a limited capacity to predict disease progression for individual patients, therefore it is important that they are evaluated for the presence of active disease when symptoms are mild or even absent, when patients are more likely to respond to new treatment interventions. It then is important to monitor responses to treatment, to quickly identify those therapies that are ineffective, modify or change therapy, and avoid disease complications. Studies are underway to assess the effects of different monitoring strategies. Because of the heavy burden of severe inflammatory bowel disease on patients' health and quality of life, and the association between intestinal healing and disease progression in high-risk patients, a treat-to-target strategy (based on tissue healing) is likely to be optimal. Crohn's disease and ulcerative colitis are heterogeneous inflammatory bowel diseases, and therapeutic requirements vary among patients. We have a limited capacity to predict disease progression for individual patients, therefore it is important that they are evaluated for the presence of active disease when symptoms are mild or even absent, when patients are more likely to respond to new treatment interventions. It then is important to monitor responses to treatment, to quickly identify those therapies that are ineffective, modify or change therapy, and avoid disease complications. Studies are underway to assess the effects of different monitoring strategies. Because of the heavy burden of severe inflammatory bowel disease on patients' health and quality of life, and the association between intestinal healing and disease progression in high-risk patients, a treat-to-target strategy (based on tissue healing) is likely to be optimal. Vipul JairathView Large Image Figure ViewerDownload Hi-res image Download (PPT)Barrett G. LevesqueView Large Image Figure ViewerDownload Hi-res image Download (PPT) Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) that vary in severity, extension of lesions, disease activity over time, damage progression, complications, and extraintestinal manifestations. Given their heterogeneous nature, therapeutic requirements vary considerably among patients. An optimal personalized medicine approach would predict the disease course and enable tailored treatment plans based on robust predictors. However, assays for factors associated with disease course, mostly identified in retrospective studies, are not precise enough to individualize therapy in clinical practice.1Beaugerie L. Seksik P. Nion-Larmurier I. et al.Predictors of Crohn's disease.Gastroenterology. 2006; 130: 650-656Abstract Full Text Full Text PDF PubMed Scopus (507) Google Scholar, 2Loly C. Belaiche J. Louis E. Predictors of severe Crohn's disease.Scand J Gastroenterol. 2008; 43: 948-954Crossref PubMed Scopus (177) Google Scholar Accepting our limited capacity to predict disease progression in individual patients, we adapt therapies based on disease activity or development of complications.3Dignass A. Van Assche G. Lindsay J.O. et al.The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management.J Crohns Colitis. 2010; 4: 28-62Abstract Full Text Full Text PDF PubMed Scopus (931) Google Scholar, 4Dignass A. Lindsay J.O. Sturm A. et al.Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management.J Crohns Colitis. 2012; 6: 991-1030Abstract Full Text Full Text PDF PubMed Scopus (518) Google Scholar Therefore, adequate monitoring is essential to make timely decisions. Monitoring is key to identifying disease flares when symptoms are mild, the disease has a lower impact on quality of life, and is more likely to respond to new treatment interventions. Monitoring also is essential after introduction of a new therapy.5Papay P. Ignjatovic A. Karmiris K. et al.Optimising monitoring in the management of Crohn's disease: a physician's perspective.J Crohns Colitis. 2013; 7: 653-669Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 6Peyrin-Biroulet L. Sandborn W. Sands B.E. et al.Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target.Am J Gastroenterol. 2015; 110: 1324-1338Crossref PubMed Scopus (148) Google Scholar, 7Panes J. O'Connor M. Peyrin-Biroulet L. et al.Improving quality of care in inflammatory bowel disease: what changes can be made today?.J Crohns Colitis. 2014; 8: 919-926Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Because therapies are not effective in all patients, it is important to monitor response to quickly identify treatments that are ineffective, modify or change therapy, and avoid disease complications. Adequate monitoring of IBD based on timely and judicious use of assays, followed by introduction of appropriate therapies, are the best tools to modify the course of IBD. We review tools for monitoring IBD, including clinical assessment, endoscopy, cross-sectional imaging, and biomarkers. The first step of monitoring IBD is to assess symptoms. Moderate and severe (but not always mild) symptoms are reported commonly by patients.8Schreiber S. Panes J. Louis E. et al.Perception gaps between patients with ulcerative colitis and healthcare professionals: an online survey.BMC Gastroenterol. 2012; 12: 108Crossref PubMed Scopus (0) Google Scholar A proportion of patients with IBD consider mild symptoms to be normal. It is concerning that 38% of health care professionals also believe that remission does not necessarily mean complete absence of IBD symptoms.8Schreiber S. Panes J. Louis E. et al.Perception gaps between patients with ulcerative colitis and healthcare professionals: an online survey.BMC Gastroenterol. 2012; 12: 108Crossref PubMed Scopus (0) Google Scholar Even mild symptoms are associated with a reduced quality of life in UC9Panes J. Su C. Bushmakin A.G. et al.Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes.BMC Gastroenterol. 2015; 15: 14Crossref PubMed Google Scholar or CD.10Feagan B.G. Hanauer S.B. Coteur G. et al.Evaluation of a daily practice composite score for the assessment of Crohn's disease: the treatment impact of certolizumab pegol.Aliment Pharmacol Ther. 2011; 33: 1143-1151Crossref PubMed Scopus (0) Google Scholar A direct relationship has been shown between quality of life and disease activity; quality of life begins to decrease in patients with UC with Mayo scores of 2 or higher,9Panes J. Su C. Bushmakin A.G. et al.Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes.BMC Gastroenterol. 2015; 15: 14Crossref PubMed Google Scholar and in patients with a CD activity index (CDAI) score of 160 or higher.10Feagan B.G. Hanauer S.B. Coteur G. et al.Evaluation of a daily practice composite score for the assessment of Crohn's disease: the treatment impact of certolizumab pegol.Aliment Pharmacol Ther. 2011; 33: 1143-1151Crossref PubMed Scopus (0) Google Scholar There can be discrepancies between the presence of active inflammatory lesions and clinical symptoms, more so in CD than in UC. Various studies have shown a high correlation between the full Mayo score, which has an endoscopic component, and the partial Mayo score, based only on the assessment of the number of stools, presence of blood in the stool, and physician's global assessment.9Panes J. Su C. Bushmakin A.G. et al.Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes.BMC Gastroenterol. 2015; 15: 14Crossref PubMed Google Scholar In addition, a high correlation has been observed between activity indices that have an endoscopic component, such as the UC Disease Activity Index or the St. Mark's index, and indices without an endoscopic component, such as the Simple Clinical Colitis Activity Index or the Seo index. Factor analysis showed that this is because the endoscopy items in composite indices correlate with stool frequency and stool blood items.11Higgins P.D. Schwartz M. Mapili J. et al.Is endoscopy necessary for the measurement of disease activity in ulcerative colitis?.Am J Gastroenterol. 2005; 100: 355-361Crossref PubMed Scopus (0) Google Scholar In patients with CD, there is greater discrepancy between the presence of active inflammatory lesions and symptoms. Two studies showed that 18% of patients with clinical symptoms (CDAI scores > 220) did not have significant lesions at endoscopy.12Rutgeerts P. Colombel J. Schreiber S. et al.Treatment of Crohn's disease (CD): response to Remicade (infliximab) in the ACCENT I trial through week 54.Am J Gastroenterol. 2001; 96: S303Crossref PubMed Google Scholar, 13Colombel J.F. Sandborn W.J. Reinisch W. et al.Infliximab, azathioprine, or combination therapy for Crohn's disease.N Engl J Med. 2010; 362: 1383-1395Crossref PubMed Scopus (1430) Google Scholar This discrepancy may be even higher after a therapeutic intervention; results of the Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease (SONIC) showed that after treatment with tumor necrosis factor (TNF) antagonists and/or an immunosuppressant, 47% of patients in clinical remission (CDAI score < 150) still have severe endoscopic lesions, whereas 35% of those with persistent symptoms suggestive of active disease (CDAI score > 150) do not have ulcers.14Peyrin-Biroulet L. Reinisch W. Colombel J.F. et al.Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's disease in the SONIC trial.Gut. 2014; 63: 88-95Crossref PubMed Scopus (143) Google Scholar Therefore, for CD, symptoms alone cannot identify those with active disease, or those in remission, with sufficient levels of sensitivity or specificity to establish an optimal treatment plan. Nevertheless, tight clinical assessment of patients with CD is a key component of monitoring. This is supported by the Randomised Evaluation of an Algorithm for Crohn's Treatment (REACT),15Khanna R. Levesque B.G. Bressler B. et al.Early combined immunosuppression for the management of Crohn's disease: a community-based cluster randomized trial.J Crohns Colitis. 2014; 8: S2-S3Abstract Full Text PDF Google Scholar which found that after 24 months, patients receiving tight clinical monitoring followed by early treatment interventions had fewer surgeries, hospitalizations, and serious complications compared with patients receiving conventional management. Monitoring endoscopic end points is rooted in the history of IBD clinical trials. In 1955, Truelove and Witts16Truelove S.C. Witts L.J. Cortisone in ulcerative colitis. Final report on a therapeutic trial.Br Med J. 1955; 2: 1041-1048Crossref PubMed Google Scholar evaluated UC disease activity in a clinical trial of hydrocortisone using end points that included stool frequency, hemoglobin level, fever, weight gain, and endoscopic assessment. Three decades later, Schroeder et al17Schroeder K.W. Tremaine W.J. Ilstrup D.M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.N Engl J Med. 1987; 317: 1625-1629Crossref PubMed Google Scholar presented results that led to the development of a scoring system for monitoring UC activity in a trial of mesalamine. The resulting Mayo clinic score includes the patient-reported outcomes of stool frequency and rectal bleeding, which have evolved into next-generation, 2-item, patient-reported outcome end points. The UC Endoscopic Index of Severity recently was developed by a formal quantitative validation process.18Travis S.P. Schnell D. Krzeski P. et al.Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS).Gut. 2012; 61: 535-542Crossref PubMed Scopus (149) Google Scholar The score results from an 8-point instrument that considers erosions and ulcers (0–3), bleeding (0–3), and vascular pattern (0–2), although cut-off values for endoscopic improvement have not yet been defined. Central reading of endoscopic assessment of UC end points has been shown to provide strong inter-rater and intrarater reliability for the Mayo Endoscopic assessment and the UC Endoscopic Index of Severity.19Feagan B.G. Sandborn W.J. D'Haens G. et al.The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis.Gastroenterology. 2013; 145: 149-157 e2Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar In clinical trials, use of endoscopy activity indices and central reading reduces variation in end points. In clinical practice, use of endoscopic indices of activity might lead to more consistent reporting of activity between visits or among clinicians. However, to visualize the endoscopic descriptors adequately, it is important to have adequate insufflation, slow withdrawal, and sufficient washing to eliminate adherent mucus and stool during the endoscopy. Endoscopic improvement is an achievable target for patients with UC receiving biologic and combination therapies, shown in trials in UC and CD.20Rutgeerts P. Sandborn W.J. Feagan B.G. et al.Infliximab induction and maintenance therapy for ulcerative colitis.N Engl J Med. 2005; 353: 2462-2476Crossref PubMed Scopus (0) Google Scholar, 21Sandborn W. van Assche G. Reinisch W. et al.Adalimumab in the treatment of moderate-to-severe ulcerative colitis: ULTRA 2 trial results.Gastroenterol Hepatol (N Y). 2013; 9: 317-320PubMed Google Scholar, 22Sandborn W.J. Feagan B.G. Marano C. et al.Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis.Gastroenterology. 2014; 146 (quiz e14–e15): 85-95Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 23Panaccione R. Ghosh S. Middleton S. et al.Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis.Gastroenterology. 2014; 146: 392-400.e3Abstract Full Text Full Text PDF PubMed Scopus (261) Google Scholar Long-term outcomes such as steroid-free remission and colectomy are associated with endoscopic improvement in patients with UC. For example, the Active Ulcerative Colitis Trial (ACT1) showed that subjects who achieved a Mayo endoscopic score of 0 or 1 were more likely than those who achieved a score of 2 or 3 to avoid colectomy at week 52.24Colombel J.F. Rutgeerts P. Reinisch W. et al.Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis.Gastroenterology. 2011; 141: 1194-1201Abstract Full Text Full Text PDF PubMed Scopus (351) Google Scholar In addition, among UC patients in clinical remission, those achieving mucosal healing defined as a Mayo endoscopy score of 0 are more likely to have longer duration of clinical remission than patients without mucosal healing.25Kim J.H. Cheon J.H. Park Y. et al.Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission.Scand J Gastroenterol. 2016; 51: 1069-1074Crossref PubMed Scopus (0) Google Scholar There is debate over whether persistence of endoscopic lesions in patients with UC under complete clinical remission should prompt further therapeutic intervention. Despite the association between persistence of endoscopic lesions and worse outcomes, few studies have shown the effectiveness of any type of therapy in this situation, or the efficacy of proactively evaluating treating to symptomatic vs endoscopic targets. Risk factors for UC progression are poorly defined. Patients diagnosed with UC at a young age or with sclerosing cholangitis have a higher risk of disease progression. Progression from distal to more extensive colitis also is associated with a greater chance of steroid-refractory disease; extraintestinal manifestations; and requirements for therapies such as thiopurines, cyclosporine, and infliximab; and surgery.26Etchevers M.J. Aceituno M. Garcia-Bosch O. et al.Risk factors and characteristics of extent progression in ulcerative colitis.Inflamm Bowel Dis. 2009; 15: 1320-1325Crossref PubMed Scopus (0) Google Scholar Duration and anatomic extent of disease is a risk factor for colorectal cancer.27Farraye F.A. Odze R.D. Eaden J. et al.AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease.Gastroenterology. 2010; 138: 746-774Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar Generally, all patients with disease for 8 years or more with a minimum of distal colitis should undergo surveillance. After the initial surveillance colonoscopy, monitoring can be determined based on risk factors. Annual colonoscopy is recommended at any time point after diagnosis of primary sclerosing cholangitis and for patients with strictures within the previous 5 years.27Farraye F.A. Odze R.D. Eaden J. et al.AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease.Gastroenterology. 2010; 138: 746-774Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar Signs and symptoms of CD were first monitored in clinical trials using the CDAI.28Best W.R. Becktel J.M. Singleton J.W. et al.Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study.Gastroenterology. 1976; 70: 439-444Abstract Full Text PDF PubMed Google Scholar However, CDAI scores do not correlate with active inflammation measured by endoscopy.29Cellier C. Sahmoud T. Froguel E. et al.Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives.Gut. 1994; 35: 231-235Crossref PubMed Google Scholar Improvements detected by endoscopy, specifically deep remission (absence of ulcers and CDAI <150), were associated with better long-term outcomes, such as fewer hospitalizations and surgeries and increased health-related quality of life in the extend the safety and efficacy of adalimumab through endoscopic healing (EXTEND) trial. Biologic therapies can produce endoscopic improvement, shown in the Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease,25Kim J.H. Cheon J.H. Park Y. et al.Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission.Scand J Gastroenterol. 2016; 51: 1069-1074Crossref PubMed Scopus (0) Google Scholar EXTEND,30Rutgeerts P. Van Assche G. Sandborn W.J. et al.Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial.Gastroenterology. 2012; 142: 1102-1111 e2Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar and endoscopic mucosal improvement in patients with active Crohn's disease treated with certolizumab pegol (MUSIC) trials.31Hebuterne X. Lemann M. Bouhnik Y. et al.Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol.Gut. 2013; 62: 201-208Crossref PubMed Scopus (0) Google Scholar Endoscopic scoring offers an alternative to endoscopic monitoring by the presence of ulcerations. The Simple Endoscopic Score for CD was simplified from the Crohn's disease endoscopic index of severity (CDEIS) but remains complex, although it is scored reliably by central readers.32Khanna R. Zou G. D'Haens G. et al.Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn's disease.Gut. 2016; 65: 1119-1125Crossref PubMed Scopus (14) Google Scholar However, its performance in nonexpert hands is unclear. Less is known about the potential role for small-bowel and capsule endoscopy in monitoring CD. Mucosal healing has been assessed by capsule endoscopy in 2 small prospective studies.33Hall B. Holleran G. Chin J.L. et al.A prospective 52 week mucosal healing assessment of small bowel Crohn's disease as detected by capsule endoscopy.J Crohns Colitis. 2014; 8: 1601-1609Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 34Niv E. Fishman S. Kachman H. et al.Sequential capsule endoscopy of the small bowel for follow-up of patients with known Crohn's disease.J Crohns Colitis. 2014; 8: 1616-1623Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Verification of small-bowel patency with cross-sectional imaging is required.35Panes J. Bouhnik Y. Reinisch W. et al.Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines.J Crohns Colitis. 2013; 7: 556-585Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar, 36Annese V. Daperno M. Rutter M.D. et al.European evidence based consensus for endoscopy in inflammatory bowel disease.J Crohns Colitis. 2013; 7: 982-1018Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar The reliability of capsule endoscopy in evaluation of the colon also recently was evaluated.37D'Haens G. Lowenberg M. Samaan M.A. et al.Safety and feasibility of using the second-generation pillcam colon capsule to assess active colonic Crohn's disease.Clin Gastroenterol Hepatol. 2015; 13: 1480-1486 e3Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Cost-effectiveness analysis of small-bowel capsule endoscopy found it to be a relatively low-value test in most scenarios, after colonoscopy and cross-sectional imaging are performed for diagnosis of CD.38Levesque B.G. Cipriano L.E. Chang S.L. et al.Cost effectiveness of alternative imaging strategies for the diagnosis of small-bowel Crohn's disease.Clin Gastroenterol Hepatol. 2010; 8 (e1–4): 261-267Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Capsule endoscopy might be used in disease monitoring. Despite the association between persistence of endoscopic lesions and poor outcomes, few interventional studies have shown the effectiveness of treatment intensification in patients with CD in complete remission but with persistent ulcerations. This is complicated further by evidence that patients with ulcers may not have the same outcomes without anti-TNF agents vs when they receive anti-TNF agents or thiopurines.39Allez M. Lemann M. Bonnet J. et al.Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy.Am J Gastroenterol. 2002; 97: 947-953Crossref PubMed Scopus (0) Google Scholar Furthermore, it is unclear whether treating based on clinical symptoms or endoscopic targets is more effective—this will be evaluated in large randomization trials such as REACT 2.40Enhanced algorithm for Crohn's treatment incorporating early combination therapy (REACT2). Available from: https://clinicaltrials.gov/ct2/show/NCT01698307. Accessed September 10, 2016.Google Scholar Progression of damage is better established for patients with CD, and is related to development of stricturing lesions, penetrating complications, and permanent loss of bowel related to resection. The Lémann index was developed to measure bowel damage; scores are based on objective assessments of strictures, penetrating complications, and resected segments, using a combination of endoscopy and cross-sectional imaging techniques.41Pariente B. Cosnes J. Danese S. et al.Development of the Crohn's disease digestive damage score, the Lemann score.Inflamm Bowel Dis. 2011; 17: 1415-1422Crossref PubMed Scopus (0) Google Scholar The diagnosis of IBD is based on endoscopic and histologic evaluations of the colon and terminal ileum, as well as their symptoms and laboratory results.42Van Assche G. Dignass A. Panes J. et al.The second European evidence-based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis.J Crohns Colitis. 2010; 4: 7-27Abstract Full Text Full Text PDF PubMed Scopus (624) Google Scholar, 43Dignass A. Eliakim R. Magro F. et al.Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis.J Crohns Colitis. 2012; 6: 965-990Abstract Full Text Full Text PDF PubMed Scopus (376) Google Scholar In CD, lesions can affect any segment of the gastrointestinal tract and extend to deep intestinal wall layers and mesentery, rendering assessment by colonoscopy incomplete. There is increasing recognition of the need for cross-sectional imaging in CD, to objectively categorize disease location, activity, behavior, and damage progression. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI)35Panes J. Bouhnik Y. Reinisch W. et al.Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines.J Crohns Colitis. 2013; 7: 556-585Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar, 44Panes J. Bouzas R. Chaparro M. et al.Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn's disease.Aliment Pharmacol Ther. 2011; 34: 125-145Crossref PubMed Scopus (0) Google Scholar detect transmural complications with high accuracy, and can be used to assess luminal inflammation and severity. MRI and US do not require radiation and increasingly are used for assessment of patients with CD.45Gourtsoyiannis N.C. Grammatikakis J. Papamastorakis G. et al.Imaging of small intestinal Crohn's disease: comparison between MR enteroclysis and conventional enteroclysis.Eur Radiol. 2006; 16: 1915-1925Crossref PubMed Scopus (0) Google Scholar Changes associated with active CD detected by MRI include intestinal wall thickening, increased contrast enhancement after administration of gadolinium, mural edema, ulcerations, mesenteric hypervascularity, lymphadenopathy, and presence of peri-enteric edema or free fluid.46Oussalah A. Laurent V. Bruot O. et al.Diffusion-weighted magnetic resonance without bowel preparation for detecting colonic inflammation in inflammatory bowel disease.Gut. 2010; 59: 1056-1065Crossref PubMed Scopus (140) Google Scholar, 47Punwani S. Rodriguez-Justo M. Bainbridge A. et al.Mural inflammation in Crohn disease: location-matched histologic validation of MR imaging features.Radiology. 2009; 252: 712-720Crossref PubMed Scopus (141) Google Scholar, 48Rimola J. Rodriguez S. Garcia-Bosch O. et al.Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease.Gut. 2009; 58: 1113-1120Crossref PubMed Scopus (296) Google Scholar, 49Rimola J. Ordas I. Rodriguez S. et al.Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity.Inflamm Bowel Dis. 2011; 17: 1759-1768Crossref PubMed Scopus (196) Google Scholar These changes are similar in all colonic segments and terminal ileum, with the exception of enlarged lymph nodes that predominantly are associated with the presence of active inflammation in the ascending colon and terminal ileum.49Rimola J. Ordas I. Rodriguez S. et al.Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity.Inflamm Bowel Dis. 2011; 17: 1759-1768Crossref PubMed Scopus (196) Google Scholar MRI not only can determine the presence or absence of active disease, but also quantify the severity. MR enterography might be less effective in detecting activity in proximal small-bowel segments than in the lower distal ileum. Abnormalities associated with inflammation in proximal segments can be detected by MR enteroclysis or MR enterography. Wall thickening, indicating active inflammation, is not always present in the jejunum. Identification of active disease in the upper small intestine therefore should rely on abnormalities on mucosal folds, changes in contrast enhancement, or detection of extra-enteric changes, such as an increased number of regional lymph nodes. Scores from an index based on quantification of motility alterations have been shown to correlate with the presence of inflammation in the terminal ileum.50Makanyanga J.C. Pendse D. Dikaios N. et al.Evaluation of Crohn's disease activity: initial validation of a magnetic resonance enterography global score (MEGS) against faecal calprotectin.Eur Radiol. 2014; 24: 277-287Crossref PubMed Scopus (27) Google Scholar One study evaluated the accuracy of MRI in assessing the severity of small-bowel CD, using small-bowel capsule endoscopy as a comparator, showing that findings of disease severity for the 2 techniques were in agreement in 75.5% of segments.51Albert J.G. Martiny F. Krummenerl A. et al.Diagnosis of small bowel Crohn's disease: a prospective comparison of capsule endoscopy with magnetic resonance imaging and fluoroscopic enteroclysis.Gut. 2005; 54: 1721-1727Crossref PubMed Scopus (0) Google Scholar Furthermore, 2 studies compared the diagnostic accuracy of MRI using double-balloon endoscopy as the reference standard. The first study found agreement in 21 of 28 segments of the small bowel evaluated.52Hyun S.B. Kitazume Y. Nagahori M. et al.Magnetic resonance enterocolonography is useful for simultaneous evaluation of small and large intestin