The objectives of this research project are: (i) development of experimental rat kidney and rat heart transplantation models; (ii) development and application of non-invasive MRI techniques to monitor organ functions in these rat models during transplant rejection; (iii) comparison of MRI results with conventional invasive techniques. Renal function in transplanted organs was assessed by the MRI measurement of renal cortical perfusion using arterial spin tagging. Quantitative measurement of renal cortical perfusion detects changes in renal function associated with surgical stress as well as acute rejection. At 3 days post-transplantation, perfusion of the transplanted kidney's cortex was similarly reduced in both syngeneic and allogeneic transplant groups. At 7 days after transplantation, cortical perfusion was at the level of background noise in the allogeneic transplant group, and was significantly lower than the non-transplanted group or the syngeneic group at the same time point, indicating that quantitative MRI can easily detect severe rejection. Cardiac function after transplantation is investigated in three models: (i) ex-vivo isolated rat heart model assessed by Langendorff perfusion; (ii) in-situ isovolumic working heart model with implanted intraventricular balloon catheter; (iii) working left heart model assesed by MRI imaging. The heterotopic rat heart transplant system is used to characterize early changes in diastolic cardiac function indicative of diminished ventricular compliance in these studies. The sensitivity of the diastolic function indices, particularly the time constant of isovolumic relaxation, t, also permits a detailed evaluation of novel immunomodulatory strategies aimed at rapid reversal of the early rejection process. Using the in-situ balloon model, left ventricular pressure-volume relationships are determined. The potential drawback of this model is the possibility for thrombus formation in the left ventricular cavity, fibrosis of endocardium, and the loss of cardiac distensibility. The working left heart model solves these problems and MRI allows non-invasive, quantitation of ventricular function. :
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