Purpose: To evaluate the utility of mural and extramural sonographic features of Crohn's Disease as potential imaging biomarkers of inflammation and fibrosis against whole-mount histological sections.
Methods: Twelve Crohn's disease patients (Mean age 35(25-69), 7 males) underwent small bowel ultrasound prior to small bowel resection. Two radiologists in consensus graded multiple parameters including mural, mucosal and submucosal thickness, submucosal/mesenteric echogenicity and clarity and mural Doppler signal in 50 selected bowel cross-sections. Matching with histological sampling sites was facilitated via scanning of the resected specimen. A histopathologist scored acute and chronic inflammation, and fibrosis (using histological scoring systems) following analysis of whole mount block sections. The association between sonographic observations and histopathological scores was examined via univariable and multivariable analysis.
Results: In univariate analyses, bowel wall thickness (regression co-efficient and 95% CI 0.8 (0.3, 1.3) p = 0.001), mesenteric fat echogenicity (8.7(3.0, 14.5) p = 0.005), submucosal layer thickness (7.4(1.2, 13.5) p = 0.02), submucosal layer clarity (4.4(0.6, 8.2) p = 0.02) and mucosal layer thickness (4.6(1.8, 7.4) p = 0.001) were all significantly associated with acute inflammation. Mesenteric fat echogenicity (674(8.67, 52404) p = 0.009), submucosal layer thickness (79.9(2.16, 2951) p = 0.02) and mucosal layer thickness (13.6(1.54, 121) p = 0.02) were significantly associated with chronic inflammation. Submucosal layer echogenicity (p = 0.03), clarity (25.0(1.76, 356) p = 0.02) and mucosal layer thickness (53.8(3.19, 908) p = 0.006) were significantly associated with fibrosis. In multivariate analyses, wall and mucosal thickness remained significantly associated with acute inflammation (p = 0.02), mesenteric fat echogenicity with chronic inflammation (p = 0.009) and mucosal thickness (p = 0.006) with fibrosis.
Conclusion: Multiple sonographic parameters are associated with histological phenotypes in Crohn's disease although there is overlap between ultrasonic stigmata of acute inflammation, chronic inflammation and fibrosis.
Keywords: Crohn’s disease; Fibrosis; Inflammation; Ultrasound.