Assessment of renal fibrosis with diffusion-weighted MR imaging: Study with murine model of unilateral ureteral obstruction

Purpose: To test, in a murine model of unilateral ureteral obstruction (UUO), whether the magnetic resonance (MR) imaging-derived apparent diffusion coefficient (ADC) changes during the progression of renal fibrosis and correlates with the histopathologic changes observed in renal fibrogenesis. Materials and Methods: This study was approved by the institutional animal care and use committee. A UUO was created in each of 14 mice. In five mice, longitudinal diffusion-weighted (DW) imaging was performed before the UUO (day 0) and on days 3 and 7 after the UUO and was followed by histopathologic analysis. The nine remaining mice were examined with cross-sectional studies on days 0 ( n = 4) and 3 ( n = 5). ADCs were measured with a spin-echo echo-planar sequence at five b values ranging from 350 to 1200 sec/mm². Differences in ADC among the time points and between the sides were assessed by using Tukey-Kramer and Student t tests, respectively. ADC was correlated with cell density and α-smooth muscle actin (α-SMA, a marker of myofibroblasts) expression at linear regression analysis. Results: Histopathologic examination revealed typical renal fibrosis on the side with UUO. The ADC decreased over time on the UUO side, from (1.02 ± 0.06 [standard deviation]) x 10^-3 mm²/sec on day 0 to (0.70 ± 0.08) x 10^-3 mm²/sec on day 3 (P < .001) and (0.57 ± 0.10) x 10^-3 mm²/sec on day 7 (P < .001). The percentage change in ADC was greater on the UUO side than on the contralateral side on days 3 (29% ± 9, P = .05) and 7 (44% ± 11, P < .01). ADC correlated with both increased cell density and increased α-SMA expression (P < .001 for both correlations). Conclusion: An ADC decrease in renal fibrosis is associated with an increased number of cells, including fibroblasts. ADC has the potential to serve as a sensitive noninvasive biomarker of renal fibrosis.