The method of choice for clinically detecting cardiac allograft rejection is the endomyocardial biopsy. Although this method is the """"""""gold standard"""""""" for determining cardiac allograft rejection in patients, it is suboptimal because cell death must occur before rejection can be diagnosed and augmented immunotherapy initiated. It would be desirable to monitor the rejection process at a metabolic level, and detect rejection or reversal of these metabolic events, noninvasively, possibly even before any significant myocyte loss occurs. With the progressive lowering of recipient age for cardiac transplantation, infants and neonates are now undergoing this therapy. The difficulty and potential dangers of routine endomyocardial biopsy techniques in very young and very small patients has underscored the need for truly noninvasive methods that are highly sensitive to detecting cardiac rejection. The overall goal of this proposal is to investigate the utility of serial phosphorous-31 (31P) nuclear magnetic resonance spectroscopy (NMRS or MRS) for the detection of cardiac allograft rejection in patients. The hypothesis to be tested is that alterations occur in the bioenergetic state of the transplanted heart, that these alterations are detectable by 31P NMRS, and that this information would be of clinical value. To test this hypothesis, this proposal has three specific aims.
Specific Aim #1. To evaluate early acute cardiac transplant rejection in patients using serial, image-guided, 31P 1D chemical shift imaging (1DCSI) which will obtain multiple NMR spectra across the heart and to correlate these findings with endomyocardial biopsy data.
Specific Aim #2. To evaluate late acute cardiac transplant rejection in patients using serial, image-guided, 31P 1D chemical shift imaging (1DCSI) which will obtain multiple NMR spectra across the heart and to correlate these findings with endomyocardial biopsy data.
Specific Aim #3. To evaluate the use of ultra-high field NMR (4.1T), which provides a higher degree of spatial resolution, in pilot studies of both early acute and late acute cardiac transplant rejection and correlate these findings with data obtained at 1.5T. A key strategy of this application is the serial evaluation of cardiac transplant patients at 1.5T by 31P NMRS. A single 31P spectrum compared to biopsy data will unlikely correlate because the comparison being made is between the bioenergetic state of the transplanted heart and the immune response of the host. This comparison may not correspond directly in time; however multiple spectra obtained over time should better define the biopsy/31P NMRS relationship.
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