P0040 Measurement of collagen concentration throughout the intestinal layers using Deep Learning: implications in Inflammatory Bowel Disease (IBD)
Authors: Tsounis E , Forlano R , Voulgaris T , Bosgana P , Tsakai O , Giannakeas N , Kalafateli M , Aggeletopoulou I , Pastras P , Diamantopoulou G , Tsolias C , Melachrinou M , Thomopoulos K , Theocharis G , Tzallas A , Goldin R , Manousou P , Triantos C 
Published: January 2025

Abstract

Background
IBD, particularly Crohn’s disease (CD), is marked by recurrent episodes of inflammation, leading to fibrosis and collagen deposition throughout the intestinal layers.1,2 In this study, we aim to quantify collagen levels across the distinct layers of the gut and examine their correlation with clinical characteristics and disease outcomes.

Methods
A total of 190 IBD patients were enrolled, including 98 with Ulcerative Colitis (UC) and 92 with CD (60% male; median age: 42 years, IQR: 29–48; follow-up: 110 months, IQR: 39-181), plus 73 controls. Biopsies were collected, stained with Sirius Red, and digitized. A total of 612 biopsies were included. Intestinal layers in biopsy images from the derivation group were manually annotated to train a mask Region-based Convolution Neural Network (mask R-CNN), which uses ResNet-101 backbone. After the detection of intestinal layers by the trained model, K-means was employed at the pixel level, to segment and quantify Collagen Proportionate Area (CPA) regions in each layer. Follow-up biopsies (&gt;6 months) were available for 85 patients. Multivariate Cox regression was used to assess the risk of adverse outcomes, including variables with p&lt;0.05 from the univariate analysis.

Results
Submucosal collagen was significantly correlated with mucosal CPA (r=0.36; p&lt;0.001) and CPA in the muscular layer (r=0.54; p&lt;0.001), as well as with C-reactive protein (r=0.38; p=0.001) and erythrocyte sedimentation rate (r=0.53; p=0.005). In CD, submucosal CPA showed a positive association with disease activity as measured by the Crohn’s Disease Activity Index (CDAI) (r=0.31; p=0.005), endoscopic activity assessed by the Simple Endoscopic Score for CD (SES-CD) (r=0.32; p=0.004), and Nancy histologic activity score (r=0.25; p=0.046). In UC, the Full Mayo score showed a trend with submucosal CPA, but it did not reach significance (r=0.13; p=0.09). Patients requiring treatment with biologics had higher baseline submucosal CPA levels (mean difference: 12; 95%CI: -0.6 to 24.6; p=0.06). Patients treated with biologics at follow-up biopsies (19/85) experienced a significantly greater reduction in submucosal CPA (-21.1; 95% CI: -38.3 to -3.9) compared to those not receiving biologics (-1.7; 95% CI: -9.4 to 6.1; p = 0.039). Baseline submucosal CPA was independently associated with an increased risk of surgery in CD patients during follow-up (aHR=1.03; 95%CI: 1.002–1.06; p=0.048), along with B2/B3 disease behavior (p=0.003) and elevated CDAI (p=0.004) (Table I).

Conclusion
Submucosal collagen levels correlate with clinical, endoscopic, and histologic activity in CD, potentially serving as a prognostic marker for long-term outcomes. Emerging therapies may help reduce collagen accumulation and its associated complications.

References
1.Mak JWY, Ng SC. Epidemiology of fibrostenosing inflammatory bowel disease. J Dig Dis. 2020;21(6):332-335. doi:10.1111/1751-2980.12853
2.Rieder F, Mukherjee PK, Massey WJ, Wang Y, Fiocchi C. Fibrosis in IBD: from pathogenesis to therapeutic targets. Gut. 2024;73(5):854-866. Published 2024 Apr 5. doi:10.1136/gutjnl-2023-329963