Using intra-voxel incoherent motion MRI to dynamically evaluate the attenuating effects of donafenib combined with carvedilol in a thioacetamide-induced hepatic fibrosis rat model.

Abstract

Objective: This study aimed to dynamically evaluate the attenuating effects of donafenib combined with carvedilol using intra-voxel incoherent motion (IVIM) MRI at different time points of disease course in a thioacetamide (TAA)-induced hepatic fibrosis rat model.

Methods: In this study, 40 male Sprague-Dawley rats received TAA for 6 weeks to induce liver fibrosis and were divided into four groups randomly (N = 10). From week 3 to week 6 of modeling, each group of rats received daily gavage of vehicle, carvedilol (CARV), donafenib (DON), and donafenib plus carvedilol (DON + CARV), respectively. IVIM MRI was used to assess the degree of liver fibrosis in the above groups at 0, 2, 4, and 6 weeks after modeling. Liver fibrosis was classified according to the METAVIR scoring system (F0-F4). IVIM parameters were calculated using a biexponential fitting model, and a least-squares fitting approach was applied for parameter estimation.

Results: The mean pathological collagen areas and the expression of α-SMA and collagen I in the CARV, DON, and DON + CARV groups were significantly less than that in the vehicle group (P < 0.001). IVIM-derived parameters (D, D^*, and f) and ADC values were negatively correlated with the fibrosis levels (D: r² = 0.594, P < 0.001; D^*: r² = 0.556, P < 0.001; f: r² = 0.737, P < 0.001; ADC: r² = 0.694, P < 0.001). At 4 and 6 weeks after modeling, the mean IVIM parameters and ADC values of the DON + CARV group were significantly higher than those of the vehicle group.

Conclusion: IVIM MRI is a noninvasive and valuable dynamic monitoring tool for liver fibrosis, and it was useful to monitor the dynamic inhibition process of donafenib and carvedilol on liver fibrosis in a TAA-induced rat model.