Using functional magnetic resonance imaging to evaluate an acute allograft rejection model in rats

Purpose To assess the longitudinal changes of allograft pathophysiology by intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) MRI in a rat model of acute renal allograft rejection. Materials and methods Acute rejection (AR) was induced by transplantation of Dark Agouti donor kidneys into Lewis recipients (n = 18). A Lewis-Lewis rat syngeneically transplanted (sTX) model served as the control (n = 6). Acute tubular necrosis (n = 6) and acute calcineurin inhibitor toxicity (n = 6) groups were established using Lewis rats. MRI was performed on postoperative day (POD) 1, 4 and 7 in the allogeneically transplanted (aTX) group and on POD4 in the other groups. Histological evaluation and PCR were performed. Results After the allogenic transplantation, all MRI parameters of allograft further decreased until POD7, and the D and ADC values in the cortex were significantly lower than that in the sTX group (1.03 ± 0.09 vs 1.52 ± 0.09 × 10−3 mm2/s, Padj < 0.05; 1.21 ± 0.03 vs 1.78 ± 0.07 × 10−3 mm2/s, Padj < 0.05). The D*, f and R2* values of the aTX group in the cortex and medulla were significantly lower than those in the sTX group on POD7 (cortex, D*: 25.60 ± 4.78 vs 69.32 ± 9.79 × 10−3 mm2/s, Padj < 0.05; f: 7.84 ± 1.83 vs 20.34 ± 3.08%, Padj < 0.05; R2*: 16.61 ± 4.18 vs 31.48 ± 6.43 1/s, Padj < 0.05; medulla, D*: 13.59 ± 6.08 vs 62.75 ± 9.20 × 10−3 mm2/s, Padj < 0.05; f: 7.46 ± 1.62 vs 14.68 ± 2.05%, Padj < 0.05; R2*: 21.59 ± 3.45 vs 39.53 ± 4.34 1/s, Padj < 0.05). AR grafts presented serve interstitial inflammation, tubulitis and infiltration of T-lymphocytes and macrophages. The MRI parameters, including D, ADC, D*, f and R2*, were significantly correlated with the histological changes, cell infiltration and inflammatory cytokine mRNA levels. Conclusions IVIM coupled with BOLD MRI allows longitudinal assessment of allograft diffusion, perfusion and oxygen consumption impairment caused by acute renal allograft rejection in rat model.