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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK068751-01
Application #
6827742
Study Section
Special Emphasis Panel (ZDK1-GRB-1 (M1))
Program Officer
Laughlin, Maren R
Project Start
2004-09-01
Project End
2006-08-30
Budget Start
2004-09-01
Budget End
2005-08-30
Support Year
1
Fiscal Year
2004
Total Cost
$188,750
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Virostko, John; Radhika, Aramandla; Poffenberger, Greg et al. (2010) Bioluminescence imaging in mouse models quantifies beta cell mass in the pancreas and after islet transplantation. Mol Imaging Biol 12:42-53
Virostko, John; Powers, Alvin C (2009) Molecular imaging of the pancreas in small animal models. Gastroenterology 136:407-9
Powers, Alvin C (2008) Insulin therapy versus cell-based therapy for type 1 diabetes mellitus: what lies ahead? Nat Clin Pract Endocrinol Metab 4:664-5