Monitoring neovascularization of intraportal islet grafts by dynamic contrast enhanced magnetic resonance imaging

Islets. 2009 Nov-Dec;1(3):249-55. doi: 10.4161/isl.1.3.9862.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Contrast Media*
  • Diabetes Mellitus, Experimental / diagnostic imaging
  • Diabetes Mellitus, Experimental / surgery
  • Diabetes Mellitus, Type 1 / diagnostic imaging*
  • Diabetes Mellitus, Type 1 / surgery*
  • Female
  • Gadolinium
  • Graft Survival / physiology
  • Image Enhancement / methods
  • Infusions, Intravenous
  • Islets of Langerhans / diagnostic imaging
  • Islets of Langerhans Transplantation / methods*
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Physiologic / physiology*
  • Portal Vein
  • Radionuclide Imaging

Substances

  • Contrast Media
  • Gadolinium