Intravoxel incoherent motion MRI for monitoring the therapeutic response of hepatocellular carcinoma to sorafenib treatment in mouse xenograft tumor models

Background: With the introduction of targeted therapies, there has been a growing need for non-invasive imaging methods which accurately evaluate therapeutic effects and overcome the limitations of tumor size-based therapeutic response assessments. Purpose: To assess diagnostic values of intra-voxel incoherent motion (IVIM) imaging in evaluating therapeutic effects of sorafenib on hepatocellular carcinoma (HCC) using mouse xenograft model. Material and Methods: Twenty-four mice bearing Huh-7 were divided into a control group and two treatment groups received sorafenib doses of 5 mg/kg (5 mg-Tx) or 30 mg/kg (30 mg-Tx). IVIM imaging was performed using 10 b-values (0-900 s/mm 2). The apparent diffusion coefficient (ADC), diffusion coefficient (D), and perfusion fraction (f) were measured for whole tumors and tumor periphery. Changes between baseline and post-treatment parameters (Delta ADC, Delta D, and Delta f) were calculated, and these parameters were compared with microvessel density (MVD) and area of tumor cell death. Results: The post-treatment f and Delta f for tumor periphery were significantly higher in control group, followed by 5 mgTx and 30 mg-Tx (P< 0.001). MVD showed significant positive correlation with post-treatment f (r = 0.584, P = 0.003) and negative correlation with D (r = -0.495, P = 0.014) for tumor periphery, while no parameter showed significant correlation with area of tumor cell death. Conclusion: The f is significantly correlated with MVD of HCC, and could potentially be used to evaluate the antiangiogenic effects of sorafenib.