Multiparametric MRI for monitoring the therapeutic efficacy of a vascular disrupting agent (CKD-516) in rabbit VX2 liver tumors

Abstract

Objectives: To evaluate the diagnostic value of multiparametric MRI, including intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI, in the quantitative assessment of the therapeutic efficacy of a vascular disrupting agent (VDA) (CKD-516) in rabbit VX2 liver tumors Methods: In twenty-one VX2 liver tumor-bearing rabbits (15 in the treated group and 6 in the control group), IVIM-DWIs using 12 b values and DCE-MRIs were performed at a 3T scanner before and 4 hours, 24 hours, 3 days, and 7 days after CKD-516 administration. IVIM-DWI parameters including the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), and blood flow-related parameter (fD*), and DCE-MR parameters including the volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the control and treated groups as well as among different time points. Correlation between changes in tumor size and IVIM-DWI and DCE-MR parameters was analyzed to determine which MR parameters could be used as predictors for tumor response. Correlation analysis between parameters derived from IVIM-DWI and DCE-MRI was performed. Results: The treated group showed a significantly larger increase in ADC at 24 hours, a decrease of D* and fD* at 4 hours, and a decrease of f, Ktrans, and iAUC at 4 hours and 24 hours, than the control group (P<0.05). In addition, compared to baseline values, D*, f, fD*, Ktrans, and iAUC of the treated group significantly decreased at 4 hours and then, recovered at 24 hours or 3 days, and D significantly increased at 24 hours (P<0.005). The greater decrease in f and fD* at 4 hours correlated with the smaller increase in tumor size during the 7 days (rho=0.53 and 0.65, P=0.04 and 0.009, respectively). There was no significant correlation between measured parameters of IVIM-DWI and DCE-MRI (P>0.05), however, a positive correlation was observed between the relative percentage changes in fD* and Ktrans at 4 hours (rho=0.54, P=0.04). Conclusion: The therapeutic effect induced by VDA can be effectively evaluated using IVIM-DWI and DCE-MRI, and f and fD* derived from IVIM-DWI can be early predictive indicators for tumor response.