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



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.



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.



ASL allows longitudinal assessment of renal perfusion impairment due to acute and chronic renal allograft rejection in translational mouse models.



2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1664-1672.
Radiology, Hannover Medical School, Germany.
Katja
K
Hueper
Radiology, Hannover Medical School, Germany.
Martina
M
Schmidbauer
Nephrology, Hannover Medical School, Germany.
Anja
A
Thorenz
Pathology, Hannover Medical School, Germany.
Jan H
JH
Bräsen
Radiology, Hannover Medical School, Germany.
Marcel
M
Gutberlet
Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
Michael
M
Mengel
Radiology, Hannover Medical School, Germany.
Dagmar
D
Hartung
Nephrology, Hannover Medical School, Germany.
Rongjun
R
Chen
Institute of Laboratory Animal Science, Imaging Center, Hannover Medical School, Germany.
Martin
M
Meier
Nephrology, Hannover Medical School, Germany.
Hermann
H
Haller
Radiology, Hannover Medical School, Germany.
Frank
F
Wacker
Nephrology, Hannover Medical School, Germany.|The Transplantation Center of the affiliated hospital, Zunyi Medical College, Zunyi, China.
Song
S
Rong
Nephrology, Hannover Medical School, Germany.
Faikah
F
Gueler
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000601:surgery; D016030:Kidney Transplantation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012079:Renal Circulation / Q000502:physiology*; D013113:Spin Labels
D013113:Spin Labels
allograft rejection; arterial spin labeling; functional magnetic resonance imaging; kidney transplantation; perfusion