P0399 Combination of MR Cell Size Imaging and Magnetization Transfer Imaging Reflecting Intestinal Fibrosis to Predict Intestinal Disease Progression in Patients with Crohn’s Disease

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Abstract Background More than half of Crohn’s disease (CD) patients develop complications such as strictures due to intestinal fibrosis1. Intestinal fibrosis is characterized by proliferation of mesenchymal cells, especially myofibroblasts transdifferentiated from fibroblasts, and thus excessive accumulation of extracellular collagen2. Therefore, simultaneously assessing mesenchymal cells and extracellular collagen can offer a more comprehensive perspective of intestinal fibrosis and enhance predictions of disease progression. Magnetization transfer imaging (MTI) can accurately quantify intestinal collagen levels3. Recently, time-dependent diffusion MRI (TD-dMRI) demonstrated the efficacy in mapping cellular microstructures4. Methods From July 2023 through March 2024, 124 CD patients were prospectively enrolled with 31 underwent surgery at baseline. Participants underwent TD-dMRI to obtain microstructural parameters, such as cell diameter (d), intracellular volume fraction (fin), extracellular diffusivity (Dex) and Cellularity. MT-MRI were performed to obtain the normalized MT ratio (MTR) with a reported threshold of ≥0.71 indicating high collagen levels. For surgical patients, the target intestines, including diseased and normal segments were collected and myofibroblasts/fibroblasts-area-ratio was calculated to reflect mesenchymal cell states and correlated with TD-dMRI parameters. 93 nonsurgical patients were followed up for at least 6 months to evaluate intestinal disease progression. Results In 63 samples from 31 surgical patients, d had the highest correlation with myofibroblasts/fibroblasts-area-ratio (r=0.58; P<0.001). d, fin, cellularity and Dex were significantly different between diseased and normal samples (all P<0.05). Among TD-dMRI parameters, d had the highest AUC (AUC=0.86; P<0.001) for distinguishing diseased and normal samples. The optimal threshold of d was 11 μm and d≥11 μm indicated an activated profibrotic mesenchymal cell state. Therefore, 93 nonsurgical patients were divided into four groups based on the baseline d and normalized MTR: group 1 (d<11 μm, normalized MTR<0.71), group 2 (d≥11 μm, normalized MTR<0.71), group 3 (d≥11 μm, normalized MTR≥0.71), and group 4 (d<11 μm, normalized MTR≥0.71). In follow-up cohort, group 3 had the shortest disease-progression-free survival, followed by groups 2, 4, and 1 (P=0.002). Additionally, multivariable Cox regression analysis indicated that d was the only significant risk factor for disease progression (HR: 1.2; P=0.001). Conclusion TD-dMRI-derived d effectively characterizes fibrosis-associated cell features in CD, and combined with normalized MTR enables a comprehensive assessment of intestinal fibrosis and accurate prediction of disease progression. References 1.Rieder F, Zimmermann EM, Remzi FH, Sandborn WJ. Crohn’s disease complicated by strictures: a systematic review. Gut. 2013;62(7):1072-1084. doi:10.1136/gutjnl-2012-304353 2.D’Alessio S, Ungaro F, Noviello D, Lovisa S, Peyrin-Biroulet L, Danese S. Revisiting fibrosis in inflammatory bowel disease: the gut thickens. Nat Rev Gastroenterol Hepatol. 2022;19(3):169-184. doi:10.1038/s41575-021-00543-0 3.Li XH, Mao R, Huang SY, et al. Characterization of Degree of Intestinal Fibrosis in Patients with Crohn Disease by Using Magnetization Transfer MR Imaging. Radiology. 2018;287(2):494-503. doi:10.1148/radiol.2017171221 4.Zhang L, Long X, Chen L, et al. Detecting Cellular Microstructural Changes of Liver Fibrosis with Time-Dependent Diffusion MRI. Radiology. 2024;313(1):e240343. doi:10.1148/radiol.240343