4 years ago

Longitudinal evaluation of perfusion changes in acute and chronic renal allograft rejection using arterial spin labeling in translational mouse models

Michael Mengel, Frank Wacker, Song Rong, Martina Schmidbauer, Dagmar Hartung, Jan H Bräsen, Katja Hueper, Martin Meier, Rongjun Chen, Hermann Haller, Marcel Gutberlet, Anja Thorenz, Faikah Gueler
Purpose To examine the longitudinal changes of renal perfusion due to acute and chronic renal allograft rejection by using arterial spin labeling (ASL) MRI in translational mouse models of isogenic and allogenic kidney transplantation (ktx). Materials and Methods Acute rejection was induced by allogenic ktx of C57BL/6 (B6)-kidney grafts to BALB/c-recipients with prolonged cold ischemia (CIT) of 60 minutes (n = 13). To induce chronic rejection BALB/c-kidneys were transplanted into B6-recipients with short CIT of 30 minutes (n = 22). Isogenic grafts without rejection (n = 14 with prolonged, n = 9 with short CIT) and normal kidneys (n = 22) were used for comparison. Perfusion was measured on a 7T small-animal magnetic resonance imaging (MRI) scanner using flow-sensitive alternating inversion recovery (FAIR) ASL-sequences at day 1 and 6 (acute) or at week 3 and 6 (chronic) after surgery. Histological analyses of grafts included inflammation, vascular changes, and fibrosis. Results In the acute ktx model, ASL showed perfusion impairment in isogenic and allogenic kidney grafts. Perfusion of allografts further decreased until day 6 and remained stable in isografts without rejection (allogenic ktx 62 ± 21 vs. isogenic ktx 181 ± 39 ml/min/100g, P < 0.01). In the chronic ktx model, perfusion in isografts was similar to normal kidneys over the entire observation period. Perfusion was severely reduced in allografts compared to isografts (week 3: 28 ± 7 vs. 310 ± 46 ml/min/100g, P < 0.001, week 6: 32 ± 5 vs. 367 ± 72 ml/min/100g, P < 0.001). Histological analysis revealed severe inflammation, vascular occlusion, and rejection in allografts. Chronic rejection grafts showed endothelialitis, peritubular capillaritis, interstitial fibrosis, and tubular atrophy. Conclusion ASL allows longitudinal assessment of renal perfusion impairment due to acute and chronic renal allograft rejection in translational mouse models. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1664–1672.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jmri.25713

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