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.

ABSTRACT

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 = 5) and serially at 7, 14, and 21 days after sorafenib treatment. The apparent diffusion coefficient (ADCtotal ), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) at these timepoints were measured and compared between the treated (n = 15) and control group (n = 15). 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, ADCtotal 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 ADCtotal and D increased significantly at 7, 14, and 21 days compared to baseline (P < 0.05), 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. LEVEL OF EVIDENCE 1 J. Magn. Reson. Imaging 2017;45270-280.