MR Cell Size Imaging Revealing Intestinal Fibrosis to Predict Intestinal Disease Progression in Patients with Crohn's Disease.

Abstract

Background: Intestinal fibrosis in Crohn's disease (CD) is driven by mesenchymal cell activation, resulting in adverse outcomes. We aimed to evaluate the efficacy of time-dependent diffusion MRI (TD-dMRI) in characterizing fibrosis-associated cellular properties and predicting disease progression in CD.

Methods: This prospective study enrolled 145 CD patients undergoing TD-dMRI to map fibrotic cellular characteristics (e.g., cell diameter [d]). The performance of TD-dMRI was evaluated in surgical cohort 1 (31 patients, 63 specimens) based on myofibroblasts/fibroblasts-area-ratio from immunohistochemical staining, and further validated in surgical cohort 2 (21 patients, 25 specimens) using vimentin+ cells diameter from immunofluorescent staining. A follow-up cohort of 93 patients with different baseline mesenchymal cell phenotypes characterized by TD-dMRI parameter was monitored for disease progression.

Results: TD-dMRI-derived d correlated strongly with myofibroblasts/fibroblasts-area-ratio in surgical cohort 1 (r=0.58; P<0.001) and with vimentin+ cells diameter (r=0.70; P<0.001) in surgical cohort 2. d was the most discriminative parameter for distinguishing diseased and normal samples (AUC=0.86; P < 0.001), with d≥11 μm indicating profibrotic mesenchymal cell activation state. In all cohorts, d correlated positively with wall thickness and negatively with the narrowest lumen diameter and stenosis index (|r|=0.43∼0.51, all P<0.001). CD patients with d≥11 μm exhibited higher disease progression rate (33% vs. 7%; P=0.008) and shorter disease-progression-free survival (P=0.003) than those with d<11 μm. Moreover, d was the most prominent predictor for disease progression (HR: 1.3; P<0.001).

Conclusions: TD-dMRI-derived d serves as a noninvasively microstructural biomarker for intestinal fibrosis in CD, which significantly enhances the accuracy in predicting disease progression risk.