Submucosal hyper-echogenicity on intestinal ultrasound is associated with fat deposition and predicts treatment non-response in patients with ulcerative colitis

Abstract Background and Aims The submucosa is the most responsive bowel wall layer on intestinal ultrasound (IUS) when assessing treatment response in ulcerative colitis (UC). Submucosal thickening with hyper-echogenicity is observed. This study aimed to quantify echogenicity and understand transmural changes in UC. Methods 118 patients were studied in two cohorts. Cohort 1 included colectomy patients: 19 UC and 52 controls without inflammatory bowel disease. Cohort 2 included 47 UC patients in a prospective cohort starting anti-inflammatory treatment. In cohort 1, submucosal inflammation, and fat and collagen deposition were scored by two pathologists using a semi-quantitative scale (0-3). For UC patients in cohort 1, histopathology and IUS of the sigmoid were location matched. Relative submucosal echogenicity (RSE) was assessed, quantified in grayscale values. In cohort 2, baseline sigmoid RSE was compared between endoscopic responders (≥1 point decrease in endoscopic Mayo score after 8-26 weeks) and non-responders. Results In all colectomized UC patients with preserved wall layer stratification (n = 12, 63%), submucosal fat (score ≥1) was present; in those with loss of stratification (n = 7, 37%), fat was absent (score = 0). RSE was higher when fat was present (95.5 [IQR 86.5-116.9] vs. 8.1 [IQR 5.8-23.0] grayscale values, p < 0.001), with no significant differences for inflammation and collagen. In Cohort 2, RSE was higher in non-responders (n = 17) compared to responders (137.1 ± 50.9 vs. 88.3 ± 49.6 grayscale values, p = 0.003). An RSE of > 108 grayscale values predicted non-response (odds ratio: 0.07 [95% CI: 0.01-0.44], p = 0.004). Conclusion Submucosal hyper-echogenicity on IUS indicates fat deposition and predicts non-response in UC.