Pancreatic islet transplantation holds great promise for the treatment of type 1 diabetes; recent advances in islet isolation and immunosuppression have led to improved results. However, the inability to noninvasively assess islet mass or number, to quantify islet blood flow, or to image islets within the pancreas or after transplantation limit experimental approaches to increase or sustain islet mass after transplantation and hamper studies of islet function or pathology during the development of type 1 and type 2 diabetes. Using approaches involving optical imaging, biomedical engineering, and transplantation of murine and human islets, our multidisciplinary team proposes to develop and apply new imaging technology to assess islet blood flow and to image islets within the pancreas and after transplantation. The proposed studies bring two distinguished investigators from the in vivo imaging area (Gore/Lepage) to work with two investigators already working in the area of type 1 diabetes and islet biology (Powers/Piston). By bringing together scientists from different disciplines, the proposed studies apply rapidly expanding imaging technology from other areas of biology to assess islet blood flow and to image islets within the pancreas and after transplantation. Experimental approaches will include transplantation of islets into the liver or beneath the renal or hepatic capsule of an immunodeficient mouse model that allows long-term survival of murine islet grafts and human islet xenografts (NOD-SCID mice), real-time imaging of blood flow, and magnetic resonance imaging. Islet mass, survival, and function will be correlated with measurements of islet blood flow and with islet imaging and characterization by magnetic resonance. These studies should discover new information applicable to islet transplantation in humans and the examination of events that cannot be examined directly in patients who have undergone islet transplantation. These studies will lead to the ability to assess islet mass within the pancreas and after transplantation and such technology will be useful to a variety of diabetes investigators interested in type 1diabetes and islet transplantation.
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