Type 1 Diabetes results from immune mediated destruction of pancreatic beta-cells, which leads to a deficiency in insulin secretion and as a result, to hyperglycemia. Keeping blood glucose levels under tight control represents the most effective way either to prevent the onset or to reduce the progression of the chronic complications of Type 1 Diabetes. At present, pancreatic islet transplantation is emerging as the most promising clinical modality, which can stop diabetes progression without increasing the incidence of hypoglycemic events. Although early results of clinical trials using the Edmonton Protocol and its variations are very encouraging, it is still unclear how long the islets will survive and how often the transplantation procedure will be successful. In order to monitor transplantation efficiency and graft survival, reliable non-invasive imaging methods are critically needed. If such methods are introduced clinically, essential information regarding the location, function and viability of transplanted islets can be obtained repeatedly and non- invasively. We have previously shown that human pancreatic islets can be successfully labeled with laboratory-made contrast agents without altering their functions. Furthermore, using in vivo magnetic resonance imaging (MRI) we were able to detect labeled islets under the kidney capsule in a mouse model of diabetes. In this proposal we plan to bring this research to the next level and perform MR imaging studies of islet transplantation on a pre-clinical model of human disease using FDA-approved contrast media suitable for labeling human islets. In parallel, we will investigate islet survival in vivo using specific apoptotic optical imaging probes since islet apoptosis may be a significant contributing factor in the loss of transplanted islets. These results will be directly correlated to MR studies on the same animals. We anticipate that if successful, these studies can be promptly translated into clinical trials.
