title: Monitoring neovascularization of intraportal islet grafts by dynamic contrast enhanced magnetic resonance imaging.
abstract: Fifteen thousand youths are diagnosed yearly with type 1 diabetes mellitus. Pancreatic islet transplantation has been shown clinically to provide short-term (~1 year) insulin independence. However, challenges associated with early vascularization of transplanted islet grafts and long-term islet survival remain. We utilized dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to monitor neovascularization of islets transplanted into the right lobe of the liver in a syngeneic mouse model. The left lobe received no islets and served as a control. DCE data were analyzed for temporal dynamics of contrast (gadolinium) extravasation and the results were fit to a Tofts two-compartment exchange model. We observed maximal right lobe enhancement at seven days post-transplantation. Histological examination up to 28 days was used to confirm imaging results. DCE-derived enhancement strongly correlated with immunohistochemical measures of neovascularization. To our knowledge these results are the first to demonstrate, using a FDA approved contrast agent, that DCE MRI can effectively and non-invasively monitor the progression of angiogenesis in intraportal islet grafts.
authors.affiliation: Islet Transplant Laboratory; Department of Pediatrics; Loma Linda University School of Medicine; Loma Linda, CA USA.
authors.forename: Nathaniel K
authors.initials: NK
authors.lastname: Chan
authors.forename: Andre
authors.initials: A
authors.lastname: Obenaus
authors.forename: Annie
authors.initials: A
authors.lastname: Tan
authors.forename: Naoaki
authors.initials: N
authors.lastname: Sakata
authors.forename: John
authors.initials: J
authors.lastname: Mace
authors.forename: Ricardo
authors.initials: R
authors.lastname: Peverini
authors.forename: Richard
authors.initials: R
authors.lastname: Chinnock
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Sowers
authors.forename: Eba
authors.initials: E
authors.lastname: Hathout