Abstract
Purpose To develop a radiomics model based on hepatobiliary phase gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (EOB)-enhanced MRI features at the tumor margin to predict microvascular invasion in high-risk solitary hepatocellular carcinoma (HR-sHCC), determine the optimal margin region, and explore the underlying biologic mechanisms. Materials and Methods This retrospective study included patients with HR-sHCC from three medical centers between April 2015 and December 2022. Radiomics features were extracted from 121 volumes of interest (VOIs) at the tumor margin at EOB MRI. Nine combinations of statistical and machine learning methods were used to construct and validate the optimal margin region-based radiomics model. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), and patient stratification was evaluated with Kaplan-Meier and log-rank analyses. RNA sequencing data underwent differential expression analysis with DESeq2, followed by Kyoto Encyclopedia of Genes and Genomes (ie, KEGG) and Gene Ontology (ie, GO) enrichment, and immune cell infiltration was assessed using xCell and EPIC. Results A total of 436 patients (mean age, 57.7 years ± 8.8 [SD]; 352 male) were included: 254 in the training, 108 in the internal test, and 74 in the external test cohorts. Receiver operating characteristic analysis showed AUCs of 0.80 (95% CI: 0.74, 0.86), 0.76 (95% CI: 0.66, 0.85), and 0.72 (95% CI: 0.58, 0.86), respectively. The model effectively stratified patients by overall and disease-free survival (all P < .05). RNA sequencing revealed extracellular matrix remodeling, transforming growth factor-β signaling, and M2 macrophage infiltration in high optimal margin region-score tumors. Conclusion The optimal margin region-based radiomics model, derived from EOB MRI, effectively captured tumor margin heterogeneity. Keywords: MRI, Machine Learning, Radiomics, Radiogenomics, Abdomen/GI, Liver, Surgery, High-Risk Solitary Hepatocellular Carcinoma, Tumor Margin, Microvascular Invasion, Gd-EOB-DTPA-enhanced MRI, OATP1B3 © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article.