Introduction
Accurate evaluation of Crohn’s disease (CD) activity is crucial to optimise and monitor treatment. Magnetic resonance enterography (MRE) has an important role in characterising disease behaviour, but its interpretation remains subjective. Currently available validated MRE activity scores such as the simplified magnetic resonance enterography index (sMARIA) often fail to capture early treatment response; changes in constituent parameters may lag behind clinical improvements by several months. Furthermore, current evaluation is based on an isolated 2D assessment of subjectively the worst area of diseased bowel rather than assessing the full disease volume. Nonetheless, reductions in bowel wall thickness are associated with treatment response, but are subjective, and small reductions may not be detected reliably. We hypothesised that disease volume may be a more responsive imaging biomarker for disease response than conventional MRE scores.
Aims & Methods
This study aimed to evaluate the technical feasibility and clinical utility of volumetric measurement of terminal ileal (TI) CD on MRE compared to an endoscopic reference standard, and sMARIA activity score. We also assessed whether volumetric changes in disease burden measured on MRE are responsive to changes induced by biologic therapy.
Patients with CD proven by histopathological analysis who prospectively underwent both MRE and ileocolonoscopy scored with Crohn's Disease Endoscopic Index of Severity (CDEIS) within 1 month were included. A board-certified abdominal radiologist placed a centreline through the lumen of the TI that defined the length of diseased bowel on the T2-weighted non-fat saturated sequence. Centrelines were used as the basis for manual segmentations of the involved bowel wall performed independently by two board-certified abdominal radiologists. If there was no disease apparent on MRE, 5 cm of “normal” bowel wall was segmented. The mean volume of disease was compared to CDEIS and sMARIA. Inter-observer agreement for segmentation was assessed using Bland-Altman analysis. We also examined a group of patients with CD who had been treated with biologics, undergone paired pre- and post- treatment MRE, and classified as treatment responders by their treating gastroenterologist based on all available clinical data (global physician assessment). We compared the volumetric burden of CD on their pre- and post- biologic treatment MRE.
Results
Thirty patients (median age of 29 (IQR 24, 34) years, 18 females) with available MRE and endoscopy were included. The mean difference of volume of disease between the 2 readers was -3.0 cm3 (limits of agreement -21.8, 15.9). The median of the mean volume of disease in those with endoscopically active terminal ileal CD (CDEIS ≥ 3, n = 15) was 20.9 cm3 (IQR 11.3, 44.0) compared to 5.7 cm3 (2.9, 9.8) with no active CD on endoscopy (n = 15). The median of the mean volume of disease of patients with active CD by sMARIA (>= 1) (n = 23) was 15.0 cm3 (8.7, 44.0) compared to 2.85 cm3 (2.6, 3.1) for those with inactive CD.
In a further group of 6 clinically responding patients, the median volume of disease on the pre-treatment scan was 28.5 cm3 (26.4, 31.3) and 11 cm3 (4.8, 16.6) on the post-treatment scan, with a median percentage difference of -110% (-147%, -51%).
Conclusion
Volumetric measurement of CD burden on MRE is a feasible method, relates to the endoscopic burden of disease, and is sensitive to changes induced by biologics. This represents a novel, objective biomarker using MRE for assessing disease activity and treatment response in CD, worthy of further validation.
References
Ordas I, Rimola J, Alfaro I, Rodriguez S, Castro-Poceiro J, Ramirez-Morros A, et al. Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn's Disease. Gastroenterology. 2019;157(2):432-9 e1.
Puylaert CAJ, Nolthenius CJT, Tielbeek JAW, Makanyanga JC, Rodriguez-Justo M, Brosens LAA, et al. Comparison of MRI Activity Scoring Systems and Features for the Terminal Ileum in Patients With Crohn Disease. AJR Am J Roentgenol. 2019;212(2):W25-W31.
Rimola J, Torres J, Kumar S, Taylor SA, Kucharzik T, Rimola J. Recent advances in clinical practice: advances in cross-sectional imaging in inflammatory bowel disease.
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Disclosure
DB is the Associate Scientific Director, GI Clinical Imaging Lead at Takeda
BB and AB are employees at Motilent, a medical imaging analysis company
AM is the CEO of Motilent
S A Taylor holds shares in Motilent