Multi-Parametric MRI for Early Detection of Renal Fibrosis and Evaluation of Therapeutic Effect of Asiatic Acid in an Experimental Rat.

Objectives: Early diagnosis and timely treatment of renal fibrosis can improve the prognosis of patients with nephropathy. We aim to investigate the utility of multi-parametric MRI for evaluating early renal fibrosis and therapeutic efficacy in a rat model.

Methods: Eighty-four male SD rats receiving tail vein injection of adriamycin doxorubicin (ADR) to establish renal fibrosis models were utilized. Twelve rats underwent pilot experiments to identify successful renal fibrosis modeling timepoints. Seventy-two were assigned to treated (AA) and untreated (ADR) groups, which were subdivided into AA-1 and ADR-1 groups (N = 6 each, underwent continuous MRI scanning at 0, 14, 21, 28, 35, 42d), AA-2 and ADR-2 groups (N = 30 each, 6 underwent MRI scanning at 0, 14, 21, 28, 35d). Repeated measures ANOVA was used to evaluate changes in parameters over time within continuous MRI scanning groups (AA-1 and ADR-1). Independent samples t test or Wilcoxon rank sum test were used to compare the differences of parameters among groups and different time points. Pearson's correlation coefficients were used to investigate relationships between renal blood flow (RBF), cortical and medullary T1, mean kurtosis (MK) and mean diffusivity (MD) values and the laboratory results, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), Smad3, and Smad7.

Results: T1 and MK values increased over time in all groups, while RBF and MD values decreased. Significant differences in all MRI parameters except medullary MK were observed between AA and ADR groups. RBF, MK, MD, and T1 values were significantly correlated with renal interstitial collagen area, α-SMA, TGF-β1, Smad3, and Smad7 (|r| = 0.5882 to 0.9756, p < 0.0001).

Conclusion: Multi-parametric MRI can enable the detection of early microstructural and functional alterations in the kidney associated with renal fibrosis and provides a means to quantify the therapeutic efficacy of interventions.