We request continued funding for the Pittsburgh NMR Center for Biomedical Research, a multi-disciplinary research center for the application of nuclear magnetic resonance (NMR) to the biomedical sciences. Our main goal is to develop and apply state-of-the-art techniques in magnetic resonance imaging (MRI) and spectroscopy (MRS) in order to obtain accurate morphological, biochemical, and physiological information relating to important biomedical problems. The central theme of the present proposal is Cell Tracking, i.e., labeling immune cells to detect and monitor inflammatory responses in-vivo by NMR. To achieve our goal, we propose 4 technological research and development (TRD) projects, 6 collaborative research (CR) projects, and 11 service projects. The proposed TRD projects include: (i) imaging immune responses in heart transplants by MRI; (ii) in-vivo cytometry using MRI; (iii) cell labeling chemistry to make in-vivo MRI a practical method; and (iv) image reconstruction and processing from limited and noisy data. The CR projects apply the various MRI techniques developed in the TRDs to important biological and medical problems, including projects to develop MRI to detect cardiac transplant rejection in rodent and pig models, to visualize phagocytic cells in a mouse brain after traumatic brain injury, to track cells in the NOD autoimmune mouse model using in-vivo 19F MRI, to visualize immune cell dynamics in a mouse model of inflammatory bowel disease, etc. A number of our TRD and CR projects are designed to transfer developments in this program to human medicine. Our ongoing research projects in both experimental organ rejection and traumatic brain injury afford important avenues for the testing of novel molecular and pharmacological approaches to these very problematic conditions. The models to which we have applied our novel MRI methods are carefully controlled and reliable, thus facilitating the reproducible testing of therapies in a pre-clinical setting that cannot otherwise be achieved except with large patient samples. Our service projects, which cover a broad spectrum in the biomedical sciences, rely on the facilities and expertise of the NMR Center. To encourage the increasing use of NMR in medicine, we offer a training program for graduate and MD/PhD students as well as postdoctoral research associates and medical fellows. A distinct feature of the NMR Center is the ability to bring together the talents of scientists from different disciplines, such as NMR, electrical and computer engineering, chemistry, physics, biochemistry, cell biology, immunology, medicine, neuroscience, radiology, and surgery, from Carnegie Mellon University, University of Pittsburgh, and other area institutions. With these unique resources, we are in position to make major contributions to the rapidly growing field of NMR in biology and medicine. Our theme of cell tracking to detect and monitor inflammatory responses in vivo is timely and important in both basic biology and clinical medicine. ?
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