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

Abstract

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/mm²). 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 (Δ ADC, Δ D, and Δ f) were calculated, and these parameters were compared with microvessel density (MVD) and area of tumor cell death.

Results

The post-treatment f and Δ f for tumor periphery were significantly higher in control group, followed by 5 mg-Tx 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 anti-angiogenic effects of sorafenib.