Pancreatic Islet Imaging and Blood Flow

描述（由申请人提供）： 胰岛移植对1型糖尿病的治疗有很大的希望;胰岛分离和免疫抑制的最新进展已经改善了结果。然而，不能无创地评估胰岛质量或数量、量化胰岛血流或对胰腺内或移植后的胰岛成像，限制了在移植后增加或维持胰岛质量的实验方法，并妨碍了在1型和2型糖尿病发展期间对胰岛功能或病理学的研究。使用涉及光学成像，生物医学工程和小鼠和人类胰岛移植的方法，我们的多学科团队提出开发和应用新的成像技术来评估胰岛血流，并在胰腺内和移植后对胰岛进行成像。拟议的研究将两名来自体内成像领域的杰出研究人员（戈尔/Lepage）与两名已经在1型糖尿病和胰岛生物学领域工作的研究人员（Powers/Piston）合作。通过汇集来自不同学科的科学家，拟议的研究应用了生物学其他领域迅速扩展的成像技术，以评估胰岛血流，并对胰腺内和移植后的胰岛进行成像。实验方法将包括将胰岛移植到肝脏中或免疫缺陷小鼠模型的肾或肝包膜下，该模型允许鼠胰岛移植物和人胰岛异种移植物（NOD-SCID小鼠）的长期存活，血流的实时成像和磁共振成像。胰岛质量、存活率和功能将与胰岛血流量的测量以及胰岛成像和磁共振表征相关。这些研究应该发现适用于人类胰岛移植的新信息，并检查无法直接检查胰岛移植患者的事件。这些研究将导致评估胰腺内和移植后胰岛质量的能力，这种技术将有助于对1型糖尿病和胰岛移植感兴趣的各种糖尿病研究人员。

DESCRIPTION (provided by applicant): 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.