Assessment of Renal Fibrosis with Diffusion-weighted MR Imaging: Study with Murine Model of Unilateral Ureteral Obstruction

Abstract

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. 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/mm(2). 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 alpha-smooth muscle actin (alpha-SMA, a marker of myofibroblasts) expression at linear regression analysis. 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) mm(2)/sec on day 0 to (0.70 +/- 0.08) x 10(-3) mm(2)/sec on day 3 (P < .001) and (0.57 +/- 0.10) x 10(-3) mm(2)/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 alpha-SMA expression (P < .001 for both correlations). 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.