Abstract
We hypothesized that multiparametric MRI is able to non-invasively assess, characterize and monitor renal allograft pathology in a translational mouse model of chronic allograft rejection. Chronic rejection was induced by allogenic kidney transplantation (ktx) of BALB/c-kidneys into C57BL/6-mice (n = 23). Animals after isogenic ktx (n = 18) and non-transplanted healthy animals (n = 22) served as controls. MRI sequences (7T) were acquired 3 and 6 weeks after ktx and quantitative T1, T2 and apparent diffusion coefficient (ADC) maps were calculated. In addition, in a subset of animals, histological changes after ktx were evaluated. Chronic rejection was associated with a significant prolongation of T1 time compared to isogenic ktx 3 (1965 ± 53 vs. 1457 ± 52 ms, p < 0.001) and 6 weeks after surgery (1899 ± 79 vs. 1393 ± 51 ms, p < 0.001). While mean T2 times and ADC were not significantly different between allogenic and isogenic kidney grafts, histogram-based analysis of ADC revealed significantly increased tissue heterogeneity in allografts at both time points (standard derivation/entropy/interquartile range, p < 0.05). Correspondingly, histological analysis showed severe inflammation, graft fibrosis and tissue heterogeneity in allogenic but not in isogenic kidney grafts. In conclusion, renal diffusion weighted imaging and mapping of T2 and T1 relaxation times enable detection of chronic renal allograft rejection in mice. The combined quantitative assessment of mean values and histograms provides non-invasive information of chronic changes in renal grafts and allows longitudinal monitoring.
Highlights
Chronic graft rejection is one of the major causes of long-term graft loss after kidney transplantation and is still poorly understood [1,2,3]
Allogenic ktx was associated with severe elevation of T1 relaxation time in all anatomical layers when compared to control kidneys (p < 0.01) as well as to isogenic kidney grafts (p < 0.001) at both time points (Figure 1A,B and Table 1)
This study shows that magnetic resonance imaging (MRI) using mapping of T1 and T2 relaxation times as well as diffusion-weighted imaging (DWI) allows the non-invasive characterization of chronic allograft rejection in mice
Summary
Chronic graft rejection is one of the major causes of long-term graft loss after kidney transplantation (ktx) and is still poorly understood [1,2,3]. The reliance on these clinical features commonly results in the late identification of chronic renal allograft nephropathy, frequently culminating in allograft loss [4]. For diagnosis of renal pathology kidney biopsy is often required as the reference standard. In the complex pathogenesis of chronic allograft damage antigen-dependent and –independent factors initiate inflammation and fibrosis of the kidney graft, classified according to the Banff criteria [5]. This procedure is prone to sampling errors, which can provide false negative results [6]. Repeated biopsies are difficult to implement due to their invasiveness and poor patient acceptance
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