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Background  To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy.    Methods  Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction ( γ ), arterial blood flow ( BF   A ), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume ( v   I ), extraction fraction, mean intracellular water molecule lifetime ( τ   C ), and fractional intracellular volume ( v   C ) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing.    Results  The WX-TK-model-derived  γ  ( P  = 0.022) and  v   I  ( P  = 0.010), and WX-ETK-model-derived  τ   C  ( P  = 0.023) and  v   C  ( P  = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived  BF   A  ( P  = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived  v   C  ( P  = 0.034,  P  = 0.038,  P  = 0.028,  P  = 0.041, respectively) were significantly associated with an increase in OS.    Conclusions  The WX-ETK-model-derived  v   C  was an effective prognostic biomarker for advanced HCC treated with sunitinib.

plos one

Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy