The go o e propose research is to develop non-invasive methods to monitor the migration of immune cells, to detect early signs of acute graft rejection in organ transplantation, and to monitor the functions of transplanted organs using rat models by magnetic resonance imaging (MRI). When organ rejection occurs, immune cells, such as T-cells and macrophages, accumulate at the rejecting graft. MRI contrast agents, e.g., dextran-coated superparamagnetic iron-oxide (SPIO) particles, can be incorporated into rat T-cells and/or macrophages by endocytosis. These labeled cells or SPIO particles can be introduced intravenously into live rats to monitor the migration of these labeled cells to the site of graft rejection. In order to accomplish our goal, we have assembled an interdisciplinary team consisting of interactive investigators with complementary backgrounds and expertise in MRI, signal image processing, organ transplantation, organ rejection, immunology, and biochemistry.
The specific aims of our proposed research are: (i) to improve the existing MRI techniques for detecting the accumulation of labeled T-cells and/or macrophages at the site of graft rejection in vivo; (ii) to develop new techniques for tracking immune cell migration by novel signal image-processing techniques; (iii) to develop more effective rat models for organ transplantation; (iv) to develop and to apply suitable MRI methods for assessing the functions of transplanted organs (such as kidneys and hearts) during various stages of the graft rejection process in rat models in vivo; and (v) to correlate MRI parameters derived from organ transplants in rat models with conventional histological and biochemical parameters used in order to assess graft rejection, in the absence and presence of immuno-suppressive drugs. Our proposed research, if successful, can improve the management of organ transplantation, thereby reducing the occurrence of chronic allograft dysfunction. Our proposed method of MRI tracking of cell migration is a general one, and can be applied to monitor the trafficking of any type cell (including those associated with autoimmune diseases), provided that these cells can be labeled with appropriate MRI contrast agents without affecting their functions and viability, and these labeled cells can be detected by MRI.
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