Chan Nathaniel K, Obenaus Andre, Tan Annie, Sakata Naoaki, Mace John, Peverini Ricardo, Chinnock Richard, Sowers Lawrence C, Hathout Eba
Islet Transplant Laboratory; Department of Pediatrics; Loma Linda University School of Medicine; Loma Linda, CA USA.
Islets. 2009 Nov;1(3):249-255.
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.
每年有1.5万名青少年被诊断出患有1型糖尿病。胰岛移植在临床上已被证明可提供短期（约1年）的胰岛素非依赖状态。然而，与移植胰岛移植物的早期血管化和胰岛长期存活相关的挑战仍然存在。我们利用动态对比增强磁共振成像（DCE MRI）来监测同基因小鼠模型中移植到肝脏右叶的胰岛的新生血管形成。左叶未接受胰岛移植，作为对照。对DCE数据进行分析，以了解造影剂（钆）外渗的时间动态，并将结果拟合到Tofts双室交换模型。我们观察到移植后7天右叶增强最大。使用长达28天的组织学检查来确认成像结果。DCE衍生的增强与新生血管形成的免疫组织化学测量结果密切相关。据我们所知，这些结果首次使用美国食品药品监督管理局（FDA）批准的造影剂证明，DCE MRI可以有效且无创地监测门静脉内胰岛移植物中血管生成的进展。
