ObjectiveThis study aimed to develop a quantitative approach to measure intratumor heterogeneity (ITH) using MRI scans and predict the pathological grading of intrahepatic mass-forming cholangiocarcinoma (IMCC).MethodsPreoperative MRI scans from IMCC patients were retrospectively obtained from five academic medical centers, covering the period from March 2018 to April 2024. Radiomic features were extracted from the whole tumor and its subregions, which were segmented using K-means clustering. An ITH index was derived from a habitat model integrating output probabilities of the subregions-based models. Significant variables from clinical laboratory-imaging features, radiomics, and the habitat model were integrated into a predictive model, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC).ResultsThe final training and internal validation datasets included 197 patients (median age, 59 years [IQR, 52-65 years]); the external validation dataset included 43 patients (median age, 58.5 years [IQR, 52.25-69.75 years]). The habitat model achieved AUCs of 0.847 (95% CI: 0.783, 0.911) in the training set and 0.753 (95% CI: 0.595, 0.911) in the internal validation set. Furthermore, the combined model, integrating imaging variables, the habitat model, and radiomics model, demonstrated improved predictive performance, with AUCs of 0.895 (95% CI: 0.845, 0.944) in the training dataset, 0.790 (95% CI: 0.65, 0.931) in the internal validation dataset, and 0.815 (95% CI: 0.68, 0.951) in the external validation dataset.ConclusionThe combined model based on MRI-derived quantification of ITH, along with clinical, laboratory, radiological, and radiomic features, showed good performance in predicting IMCC grading.Critical relevance statementThis model, integrating MRI-derived intrahepatic mass-forming cholangiocarcinoma (IMCC) classification metrics with quantitative radiomic analysis of intratumor heterogeneity (ITH), demonstrates enhanced accuracy in tumor grade prediction, advancing risk stratification for clinical decision-making in IMCC management.Key PointsGrading of intrahepatic mass-forming cholangiocarcinoma (IMCC) is important for risk stratification, clinical decision-making, and personalized therapeutic optimization.Quantitative intratumor heterogeneity can accurately predict the pathological grading of IMCC.This combined model provides higher diagnostic accuracy.