Aberrant Motility in Unaffected Small Bowel is Linked to Inflammatory Burden and Patient Symptoms in Crohnʼs Disease

Abstract

Objectives: Inflammation related enteric dysmotility has been postulated as a cause for abdominal symptoms in Crohn's disease (CD). We investigated the relationship between MRI-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 CD patients (median age 35, range 18-78) the day before MRI 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 (wellbeing, pain, diarrhea). Adjustment for age, sex, smoking and surgical history was made using multivariate linear regression.Results: Median calprotectin was 336 (range 0-1280). Mean HBI, motility mean and motility variance were 3 (range 0-16), 0.33 (0.18 to 0.51) and 0.01 (0.0014 to 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), wellbeing (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 small bowel is associated with patient symptoms and fecal calprotectin levels, supporting the hypothesis that inflammation related enteric dysmotility may explain refractory abdominal symptoms in CD.

Relationship between MRI quantified small bowel motility and abdominal symptoms in Crohn’s disease patients—a validation study

“…Previously, using a single-centre study design in 53 Crohn's subjects, Menys et al 15 reported a significant inverse correlation between motility variance and HBI (r = -0.45, p < 0.001). There was also a significant inverse correlation between motility variance and the HBI symptom components of well-being, abdominal pain and number of liquid stools (r = −0.4, p < 0.01).…”

“…15 The observers had access to both cine motility loops and anatomical small bowel images to aid ROI placement. Specifically, small bowel demonstrating the typical stigmata of CD (such as wall thickening, abnormal T 2 signal hyper enhancement etc.)…”

“…Based on the previous derivation study, 15 two motility metrics were derived from the ROIs and summed across the whole patient: (1) mean and (2) spatial variance. The original motility measure derived from registration i.e.…”

“…The movement of pixels within manually placed regions of interest (ROIs) is quantified by the registration software as a surrogate for bowel motility. 15,17,18 For the current study, a graphical user interface (MATLAB, MathWorks, Natick, MA) was used for motility analysis. Within the viewer, anonymised datasets are displayed, as both a static reference image and as a "cine" movie.…”

“…[9][10][11][12][13][14] Indeed, recent single-site data in 53 patients suggests that aberrant motility (notably a decreased variability) in apparently healthy bowel may be linked to patient symptom burden in CD. 15 If this observation could be prospectively validated, MRI quantified bowel motility could provide new insights into the aetiology of abdominal symptoms in CD, act as a target for therapeutic monitoring and possibly aid drug development.…”