Magnetic resonance cell size imaging reveals intestinal fibrosis to predict intestinal disease progression in patients with Crohn's disease.

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 magnetic resonance imaging (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 (eg, cell diameter [d]). The performance of TD-dMRI was evaluated in surgical cohort 1 (31 patients, 63 specimens) based on myofibroblast/fibroblast area ratio from immunohistochemical staining, and further validated in surgical cohort 2 (21 patients, 25 specimens) using vimentin+ cell diameter from immunofluorescent staining. A follow-up cohort of 93 patients with different baseline mesenchymal cell phenotypes characterized by TD-dMRI was monitored for disease progression.

Results: TD-dMRI-derived d correlated strongly with myofibroblast/fibroblast area ratio in surgical cohort 1 (r = 0.58; P < .001) and with vimentin+ cell diameter (r = 0.70; P < .001) in surgical cohort 2. Cell diameter d was the most discriminative parameter for distinguishing diseased and normal samples (AUC = 0.86; P < .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 < .001). CD patients with d  ≥  11 μm exhibited higher disease progression rate (33% vs. 7%; P = .008) and shorter disease-progression-free survival (P = .003) than those with d  <  11 μm. Moreover, d was the most prominent predictor for disease progression (HR: 1.3; P < .001).

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