Evaluation of Antiangiogenic and Antiproliferative Effects of Sorafenib by Sequential Histology and Intravoxel Incoherent Motion Diffusion-Weighted Imaging in an Orthotopic Hepatocellular Carcinoma Xenograft Model

Purpose: To investigate the effectiveness of intravoxel incoherent motion (IVIM) in the assessment of the therapeutic efficacy of sorafenib in an orthotopic hepatocellular carcinoma (HCC) xenograft model. Materials and Methods: Thirty-five HCC nude mouse models were established. IVIM was performed on a 1.5T MR scanner at baseline (n = 55) and serially at 7, 14, and 21 days after sorafenib treatment. The apparent diffusion coefficient (ADC(total)), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) at these timepoints were measured and compared between the treated (n = 51) and control group (n = 1). Differences in measurements among different timepoints were evaluated. Correlations between IVIM parameters and histologic features including necrotic fraction (NF) and microvessel density (MVD) were analyzed. Results: Compared to the control group, ADC(total) and D were significantly higher at each timepoint (P=0.009), while f significantly decreased at 7 days (P = 0.009) and increased at 21 days (P = 0.028) in the treated group. Serial measurements in the treated group showed that both ADC(total) and D increased significantly at 7, 14, and 21 days compared to baseline (P < 0.005), while f significantly declined at 7 days (P=0.016) and increased at 21 days (P=0.009). Significant correlations were found between ADCtotal and NF (r=0.811, P < 0.001), D and NF (r=0.838, P < 0.001), and between f and NF (r = 0.528, P = 0.017) in the treated group. Conclusion: IVIM may provide useful biomarkers for evaluating the therapeutic effects of sorafenib on HCC.