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 system. 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
authors.initials: N
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
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging / Q000601:surgery; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging* / Q000601:surgery*; D005260:Female; D005682:Gadolinium; D006085:Graft Survival / Q000502:physiology; D007089:Image Enhancement / Q000379:methods; D007262:Infusions, Intravenous; D007515:Islets of Langerhans / Q000000981:diagnostic imaging; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011169:Portal Vein; D011877:Radionuclide Imaging
chemical_list: D003287:Contrast Media; D005682:Gadolinium