Association of Signal Heterogeneity in the Hepatobiliary Phase of Gd‐ EOB ‐ DTPA ‐Enhanced MRI With Survival Outcomes and Tumor Microenvironment in Hepatocellular Carcinoma

ABSTRACT Background Hepatobiliary phase (HBP) findings on Gd‐EOB‐DTPA‐enhanced MRI (EOB‐MRI) have been proposed as biomarkers of hepatocellular carcinoma (HCC). However, the association between intratumor signal heterogeneity in HBP of EOB‐MRI and survival or tumor microenvironment remains unclear. Methods We retrospectively analyzed 167 patients who underwent hepatic resection for HCC. The coefficient of variation (CV) in HBP on preoperative EOB‐MRI was calculated as the standard deviation/mean of the intratumor signal intensity. Hyperintense area (HIA) was defined as tumor regions with signal intensity equal to or higher than the surrounding parenchyma. Associations of imaging‐defined heterogeneity (high CV with HIA) with survival and immune infiltration were evaluated. Results Multivariate analyses showed male, negative HBs‐antigen, elevated PIVKA‐II, multiple tumors, microvascular invasion, and high CV with HIA (all p < 0.05) were significant predictors of disease‐free survival, while negative HBs‐antigen, elevated PIVKA‐II, microvascular invasion, and high CV with HIA (all p < 0.05) were significant predictors of overall survival. High CV with HIA correlated with male ( p = 0.04), larger tumor size ( p < 0.01), multiple tumors ( p < 0.01), and less CD8 + T‐cell infiltration into tumor center ( p = 0.03) and invasive margin ( p = 0.048). Conclusions High CV with HIA in HBP of EOB‐MRI may serve as a novel prognostic imaging biomarker after resection and reflect an immune‐cold HCC microenvironment.