Acute cardiac transplant rejection: detection and grading with MR imaging with a blood pool contrast agent--experimental study in the rat.
OBJECTIVE
To investigate the possibility of detecting cardiac transplant rejection and determining its degree of severity with magnetic resonance (MR) imaging with a blood pool contrast agent.


METHODS
Rat allogeneic (PVG to Wistar/Kyoto, n = 9) and syngeneic (Wistar/Kyoto to Wistar/Kyoto, n = 6) heterotopic heart transplantations were performed. On the 2nd and 6th postoperative days, an ultrasmall superparamagnetic iron oxide, or USPIO, contrast agent was injected intravenously at a dose of 2 mg of iron per kilogram of body weight. The injection was followed by three-dimensional T1-weighted MR imaging of the heart grafts with an imaging time of approximately 2 minutes for each image for 44 minutes. The signal intensity (SI) was measured in the myocardium over time, and the relative enhancement was calculated. After the 6th day, the rats were sacrificed, and the morphology of the transplanted hearts was assessed histologically. The CIs for the difference of the means on day 2 and day 6 were calculated by using a bootstrap technique, and the correlation between the relative SI change and the histologically determined degree of rejection were calculated with the Spearman rank order correlation coefficient.


RESULTS
On day 6, a statistically significant difference between the groups was found at 4 minutes after injection of the contrast agent and increased with increasing time after injection. The mean percentage change in SI at the last time point for the allogeneic group on day 2 was -8.7% (SD, 8.5) and for the syngeneic group was -6.6% (SD, 6.0). On day 6, the allogeneic group had a relative SI change of 17.7% (SD, 8.7), whereas the syngeneic group had a change of -7.4% (SD, 2.6). There was a significant difference between only the two groups on day 6 (P <.001). Furthermore, in the allogeneic group the histologically determined degree of rejection correlated positively with the relative SI enhancement (r = 0.89, P <.005).


CONCLUSIONS
Acutely rejecting heart transplants can be distinguished from nonrejecting ones in an animal model with MR imaging and a blood pool contrast agent. In addition, the relative SI enhancement reflects the histologically determined degree of rejection.
D000208:Acute Disease; D000818:Animals; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D006084:Graft Rejection / Q000175:diagnosis* / Q000473:pathology; D016027:Heart Transplantation; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D009206:Myocardium / Q000473:pathology; D010087:Oxides; D051381:Rats; D011921:Rats, Inbred WKY; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide