Cardiac transplantation is an accepted method in the treatment of end stage myocardial disease. Although results have improved steadily, allograft rejection and infection in the immunosuppressed host continue to be major problems. It is critically important to be able to detect allograft rejection at an early stage and to monitor the response of the rejection process to immunosuppressive therapy. Serial endomyocardial biopsy is currently used for assessment of graft rejection. While relatively safe, the procedure has complications, is invasive, time consuming and costly in terms of manpower. It can in addition, be imprecise or misleading if tissue samples contain scar from previous biopsies. Magnetic resonance imaging has recently been applied for the assessment of the distribution and mobility of hydrogen nuclei. The technique is sensitive to changes in the distribution of water as well as other factors such as concentration of lipids and macromolecules. The technique is completely non-invasive, highly sensitive to edema and other tissue characteristics and provides tomographic image; with high resolution. The NMR approach to monitoring cardiac graft rejection is potentially more sensitive than other non-invasive methods. Preliminary data in heterotopic rat cardiac transplants, suggest proton mobility (as reflected by T1 and T2 relaxation times) is significantly prolonged in the presence of rejection. This is confirmed by preliminary studies in heterotopic canine heart transplants. The present proposal will further assess the ability of proton NMR to detect rejection and to evaluate the graft response to immunosuppressive therapy in vivo. The orthotopic monkey cardiac transplant model will be utilized for this study. T2 weighted in vivo gated myocardial imaging will be utilized in the monkey to follow serial qualitative changes that occur during the rejection process. Proton weighted T2 images will allow serial assessment of cardiac allograft rejection non-invasively. It is anticipated that magnetic resonance imaging will prove to be a useful adjunct in monitoring the rejection process in heart transplantation. Magnetic resonance imaging may decrease the need for serial endocardial biopsies.
