Kidney Transplantation Multiparametric Functional Magnetic Resonance Imaging for Assessment of Renal Allograft Pathophysiology in Mice

Objectives: The aims of this experimental study were to investigate renal allograft pathophysiology by multiparametric functional magnetic resonance imaging (MRI) and to directly correlate MRI parameters with renal histopathology in mouse models of allogenic and isogenic kidney transplantation (ktx). Materials and Methods: Allograft rejection was induced by transplantation of C57BL/6 (B6) donor kidneys into BALB/c recipients (allogenic ktx). B6 mice that received B6 kidneys served as controls (isogenic ktx). Three weeks after ktx, MRI was performed using a 7-T small-animal scanner. Flow sensitive alternating inversion recovery echoplanar imaging arterial spin labeling, multiecho turbo spin echo, and diffusion-weighted imaging sequences were acquired. Maps of renal perfusion, T2 and T1 relaxation times, and apparent diffusion coefficients were calculated. Histological changes in the kidney were evaluated according to Banff criteria. Renal cell infiltrates and fibrosis were quantified by immunohistochemistry. Differences between groups were assessed using the Mann-Whitney U test, and the correlation of MRI parameters with renal histopathology was determined by Spearman correlation analysis. Results: After allogenic, but not isogenic, ktx, animals developed acute allograft rejection. Allogenic grafts were infiltrated by macrophages and T-lymphocytes and exhibited marked renal fibrosis. Magnetic resonance imaging revealed stronger impairment of renal perfusion (56 7 vs 293 +/- 44 mL/[min x 100 g]; P < 0.01) and more pronounced increases in T2 (60.1 +/- 2.0 vs 45.7 +/- 1.2 milliseconds, P < 0.01) and T1 relaxation times (1938 +/- 53 vs 1350 +/- 27 milliseconds, P < 0.01) in allogenic than in isogenic kidneys. Apparent diffusion coefficient was reduced to 1.39 +/- 0.14 x 10(-3) mm(2)/s in kidneys with an acute rejection and was 1.83 +/- 0.05 x 10(-3) mm(2)/s in isogenic kidneys without rejection (P < 0.05). Magnetic resonance imaging parameters significantly correlated with the amount of cellular infiltration and renal fibrosis observed histologically. Conclusions: Functional MRI allows detection of acute renal allograft rejection after allogenic ktx in mice. Functional MRI parameters correlate with cell infiltrates and fibrosis. Thus, MRI may be used noninvasively and longitudinally to investigate mechanisms of renal allograft rejection and evaluate novel therapeutic strategies in experimental studies.