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Vascularization of transplanted islets must be maintained to provide long-term graft function. In vivo assessment of new vessel formation in islet grafts has been poorly documented. The purpose of this study was to investigate whether neovascularization was detectable in vivo in a Feridex-labeled murine syngeneic subcapsular islet mass using DCE MRI over 180 days. Subcapsular transplants could be visualized at post-transplant days three, seven, 14, and 28 using T2-weighted MRI and at post-transplant day 180 by immunohistochemistry. Injection of the contrast agent gadolinium (Gd)-DTPA for DCE at three, seven, and 14 days showed increased signal in the transplant area consistent with new vessel formation. Areas under contrast enhancement curves suggested peak angiogenesis at 14 days. At 180 days, there was no observable change in signal intensity after contrast injection suggesting established vascularization or islet mass reduction. Immunohistochemistry confirmed MRI and DCE findings. These data suggest that islet angiogenesis occurs early after transplantation and is likely established after one month of transplantation. This study provides an in vivo time-line of neovascularization in subcapsular islet grafts. We anticipate that contrast extravasation captured by MRI may provide useful monitoring of graft angiogenesis if reproduced in a clinically relevant intraportal model. [ABSTRACT FROM AUTHOR]

To evaluate changes in neovascularization of transplanted islets in vivo, dynamic contrast (gadolinium) enhanced magnetic resonance imaging (MRI) was used. Both iron (Feridex)-labeled and unlabeled syngeneic murine subcapsular islet grafts were studied. Differences in dynamic contrast enhancement of islet grafts were quantified after gadolinium injection at post-transplant days 3 and 14. Normalized contrast concentrations at day 14 in transplanted islets were increased relative with that on day 3. Time to peak contrast enhancement was faster by 12 min at day 14 compared to day 3 islets (while kidney and muscle peak times remained the same). Areas under the curve for contrast concentration versus time plots were larger in 14-day relative to 3-day islet grafts. In conclusion, noninvasive assessment of neovascularization is achievable. In vivo dynamic contrast-enhanced MRI can be used to detect and quantify changes in vascularization following islet transplantation. This technique may be useful in developing pro-angiogenic strategies to improve the transplantation outcome in experimental and clinical settings. [ABSTRACT FROM AUTHOR]