Gauraang Bhatnagar

CT and MR enterography in Crohn’s disease: current and future applications

current and future applications David H. Bruining, Gauraang Bhatnagar, Jordi Rimola, Stuart Taylor, Ellen M. Zimmermann, Joel G. Fletcher Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA Centre for Medical Imaging, University College, London, UK Department of Radiology, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain Division of Gastroenterology, Hepatology, and Nutrition, University of Florida College of Medicine, Gainesville, FL, USA Department of Radiology, Mayo Clinic, Rochester, MN, USA

Magnetic resonance imaging-quantified small bowel motility is a sensitive marker of response to medical therapy in Crohn's disease

Magnetic resonance enterography (MRE) can measure small bowel motility, reduction in which reflects inflammatory burden in Crohns Disease (CD). However, it is unknown if motility improves with successful treatment.

Implementation of a new CT colonography service: 5 Year experience

AIM To describe our experience using a 5 year audit of computed tomography colonography (CTC) practice and identify factors that influence diagnostic performance to guide implementation in other centres. MATERIAL AND METHODS Consecutive patients referred for CTC at a single institution over a 5 year period were identified, and reporting rates and positive predictive value (PPV) calculated for small polyps, large polyps, and colorectal cancer. Diagnostic performance was compared using the Chi-squared test, and trends over time were examined with logistic regression. The effect of faecal tagging and an intravenous spasmolytic were investigated using Fishers exact test. RESULTS In total, 4355 CTC examinations were performed. Overall reporting rates and PPV were 17% and 92%, respectively. Negative predictive value (NPV) for cancer was 99.9%. A significant decrease in reporting rate (p < 0.001) was accompanied by an increase in PPV for small polyps (p = 0.02) following the introduction of faecal tagging. Adequacy rates for CTC improved over time (96% to 99%), with improved adequacy rates when using a spasmolytic, 98% versus 96% without. A significant difference in reporting rates, but not PPV, was found between radiologists. CONCLUSION Accurate colonic investigation using CTC can be delivered safely to a high-risk patient population at a single centre. Faecal tagging and an intravenous spasmolytic improve diagnostic performance.

Changes in dynamic contrast-enhanced pharmacokinetic and diffusion-weighted imaging parameters reflect response to anti-TNF therapy in Crohn's disease

OBJECTIVE To investigate the effect of tumour necrosis factor (TNF)-α antagonists on MRI dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) parameters in Crohns disease (CD). METHODS 42 patients with CD (median age 24 years; 22 females) commencing anti-TNF-α therapy with baseline and follow-up (median 51 weeks) 1.5-T MR enterography (MRE) were retrospectively identified. MRE included DCE (n = 20) and/or multi-b-value DWI (n = 17). Slope of enhancement (SoE), maximum enhancement (ME), area under the time-intensity curve (AUC), Ktrans (transfer constant), ve (fractional volume of the extravascular-extracellular space), apparent diffusion coefficient (ADC) and ADCfast/slow were derived from the most inflamed bowel segments. A physician global assessment of disease activity (remission, mild, moderate and severe) at the time of MRE was assigned, and the cohort was divided into responders and non-responders. Data were compared using Mann-Whitney U test and analysis of variance. RESULTS Follow-up Ktrans, ME, SoE, AUC and ADCME changed significantly in clinical responders but not in non-responders, baseline {[median [interquartile range (IQR)]: 0.42 (0.38), 1.24 (0.52), 0.18 (0.17), 17.68 (4.70) and 1.56 mm(2) s(-1) (0.39 mm(2) s(-1)) vs follow-up [median (IQR): 0.15 (0.22), 0.50 (0.54), 0.07 (0.1), 14.73 (2.06) and 2.14 mm(2) s(-1) (0.62 mm(2) s(-1)), for responders, respectively, p = 0.006 to p = 0.037}. SoE was higher and ME and AUC lower for patients in remission than for those with severe activity [mean (standard deviation): 0.55 (0.46), 0.49 (0.28), 14.32 (1.32)] vs [0.32 (0.37), 2.21 (2.43) and 23.05 (13.66), respectively p = 0.017 to 0.033]. ADC was significantly higher for patients in remission [2.34 mm(2) s(-1) (0.67 mm(2) s(-1))] than for those with moderate [1.59 mm(2) s(-1) (0.26 mm(2) s(-1))] (p = 0.005) and severe disease [1.63 mm(2) s(-1) (0.21 mm(2) s(-1))] (p = 0.038). CONCLUSION DCE and DWI parameters change significantly in responders to TNF-α antagonists and are significantly different according to clinically defined disease activity status. ADVANCES IN KNOWLEDGE DCE and DWI parameters change significantly in responders to TNF-α antagonists in CD, suggesting an effect on bowel wall vascularity.

Utility of MR enterography and ultrasound for the investigation of small bowel Crohn's disease.

Cross sectional Imaging plays an increasingly important role the diagnosis and management of Crohns disease. Particular emphasis is placed on MRI and Ultrasound as they do not impart ionising radiation. Both modalities have reported high sensitivity for disease detection, activity assessment and evaluation of extra‐luminal complications, and have positive effects on clinical decision making. International Guidelines now recommend MRI and Ultrasound in the routine management of Crohns disease patients. This article reviews the current evidence base supporting both modalities with an emphasis on the key clinical questions. We describe current protocols, basic imaging findings and highlight areas in need of further research.

Perianal Sepsis in Hematologic Malignancy: MR Imaging Appearances and Distinction from Cryptoglandular Infection in Immunocompetent Patients

PURPOSE To use magnetic resonance (MR) imaging to document the appearance of perianal infection in patients with a hematologic malignancy (HM) compared with that in immunocompetent control patients. MATERIALS AND METHODS After an ethical waiver was obtained, 38 patients with an HM were matched by age and sex to 38 control patients with no history of immunocompromise or Crohn disease. Both groups had undergone MR imaging for perianal symptoms and/or systemic sepsis. Two radiologists who were blinded to the diagnosis independently reviewed the MR images and recorded the size and distribution of abscesses and/or fistula tracts, the extent of perianal edema, and the likely diagnosis. Groups were compared by using the Mann-Whitney-Wilcoxon, χ(2), or Fisher exact test. Receiver operating characteristic (ROC) curves were constructed to estimate the ability of MR imaging to help distinguish patients with an HM from control patients. RESULTS Patients with an HM had significantly greater perianal edema than did control patients (mean arc angle of anal canal involved, 220° vs 60°; P < .001). However, they had significantly lower rates of fistula (15 [39.5%] vs 35 [92.1%] of 38; P < .001). Abscesses were similar in frequency (10 [26.3%] vs 17 [44.7%] of 38; P = .15) and were unrelated to the degree of neutropenia (P = .71) or the use of chemotherapy (P = .10). Surgical treatment was rarely required in patients with an HM, either during the acute illness (four [10.5%] of 38) or thereafter (three [7.9%] of 38). MR imaging had an excellent ability to help discriminate patients with HM from immunocompetent patients (areas under the ROC curve, 0.91 and 0.97). CONCLUSION Perianal infection in patients with an HM is more likely to cause diffuse perianal edema and is less likely to cause fistulas than in immunocompetent patients. MR imaging can help distinguish patients with an HM from those without immunocompromise.

Aberrant Motility in Unaffected Small Bowel is Linked to Inflammatory Burden and Patient Symptoms in Crohn's Disease.

Background:Inflammation-related enteric dysmotility has been postulated as a cause for abdominal symptoms in Crohns disease (CD). We investigated the relationship between magnetic resonance imaging–quantified small bowel (SB) motility, inflammatory activity, and patient symptom burden. Methods:The Harvey–Bradshaw index (HBI) and fecal calprotectin were prospectively measured in 53 patients with CD (median age, 35; range, 18–78 years) the day before magnetic resonance enterography, which included a dynamic (cine), breath-hold motility sequence, repeated to encompass the whole SB volume. A validated registration-based motility quantitation technique produced motility maps, and regions of interest were drawn to include all morphologically normal SB (i.e., excluding diseased bowel). Global SB motility was correlated with calprotectin, HBI, and symptom components (well-being, pain, and diarrhea). Adjustment for age, sex, smoking, and surgical history was made using multivariate linear regression. Results:Median calprotectin was 336 (range, 0–1280). Median HBI, motility mean, and motility variance were 3 (range, 0–16), 0.33 (0.18–0.51), and 0.01 (0.0014–0.034), respectively. Motility variance was significantly negatively correlated with calprotectin (rho = −0.33, P = 0.015), total HBI (rho = −0.45, P < 0.001), well-being (rho = −0.4, P = 0.003), pain (rho = −0.27, P = 0.05), and diarrhea (rho = −0.4, P = 0.0025). The associations remained highly significant after adjusting for covariates. There was no association between mean motility and calprotectin or HBI (P > 0.05). Conclusions:Reduced motility variance in morphologically normal SB is associated with patient symptoms and fecal calprotectin levels, supporting the hypothesis that inflammation-related enteric dysmotility may explain refractory abdominal symptoms in CD.

Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial

Summary Background Magnetic resonance enterography (MRE) and ultrasound are used to image Crohns disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue. Methods We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohns disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed. Findings 284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohns disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72–86]) and presence (97% [91–99]) were significantly greater than that of ultrasound (70% [62–78] for disease extent, 92% [84–96] for disease presence); a 10% (95% CI 1–18; p=0·027) difference for extent, and 5% (1–9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85–98]) was significantly greater than that of ultrasound (81% [64–91]); a difference of 14% (1–27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86–99) with MRE and 84% (65–94) with ultrasound (difference 12% [0–25]; p=0·054). There were no serious adverse events. Interpretation Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly. Funding National Institute of Health and Research Health Technology Assessment.

A Probabilistic Method for Estimation of Bowel Wall Thickness in MR Colonography

MRI has recently been applied as a tool to quantitatively evaluate the response to therapy in patients with Crohn’s disease, and is the preferred choice for repeated imaging. Bowel wall thickness on MRI is an important biomarker of underlying inflammatory activity, being abnormally increased in the acute phase and reducing in response to successful therapy; however, a poor level of interobserver agreement of measured thickness is reported and therefore a system for accurate, robust and reproducible measurements is desirable. We propose a novel method for estimating bowel wall-thickness to improve the poor interobserver agreement of the manual procedure. We show that the variability of wall thickness measurement between the algorithm and observer measurements (0.25mm ± 0.81mm) has differences which are similar to observer variability (0.16mm ± 0.64mm).

Prognostic biomarkers to identify patients destined to develop severe Crohn’s disease who may benefit from early biological therapy: protocol for a systematic review, meta-analysis and external validation

BackgroundIt is believed increasingly that patients with severe Crohn’s disease are best treated early with biological therapy, which may ameliorate subsequent disease course and diminish long-term complications. However, we cannot predict currently which new presentations of Crohn’s disease are destined to develop severe disease so treatment cannot be targeted to the most appropriate patients. Accordingly, via systematic review and meta-analysis we aim to identify if biomarkers of disease activity are able to predict development of severe disease.Methods/designWe will search the primary literature and conference proceedings for studies of biomarkers of all types including clinical, endoscopic, radiological, faecal, urinary, serological, genetic, and histological. Precise definition of “severe” disease is elusive so we will include sensitivity analysis to account for different definitions. We will use the CHARMS checklist to frame our question and to extract data. We will extract the study design, setting, participant characteristics, biomarker(s) investigated, and study outcomes. Bias will be assessed via the PROBAST tool. We will present the results using narrative and graphical methods. We will present the summary by meta-analysis where there are sufficient studies with reasonable homogeneity, using methods appropriate to the type of data extracted. Heterogeneity will be presented via Forest and ROC plots.DiscussionIf this systematic review and meta-analysis identifies biomarkers that appear sufficiently predictive for subsequent severe disease course, we aim to combine them in a predictive model, followed by external validation using individual patient data. A predictive model able to identify new presentations of Crohn’s disease destined to develop severe disease subsequently would have considerable clinical utility for patient management.Systematic review registrationPROSPERO CRD42016029363.