In vivo magnetic resonance imaging of vascularization in islet transplantation

Abstract

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.

Figure 1. Temporal imaging of iron-labeled islets

(a) T2-weighted image at day 3 and day 14 illustrate that iron-labeled islets can be visualized (loss of signal, arrow) after implantation. (b) Volumetric analysis of the implanted islets demonstrates an unchanged islet mass with time post-transplantation. *P > 0.05, n = 4. (c) Quantitative evaluation of T2 values from islets shows no change with time post-transplantation. *P > 0.05, n = 4.

Figure 2. Representative imaging of vascularization of iron-labeled islet grafts on day 14

(a) Postcontrast magnetic resonance imaging (MRI) at day 14 shows a contrast-enhancement (red arrows) in the vicinity of labeled transplanted islets. Similar densities were not observed in the contralateral kidney. (b) Expanded view of ‘A’ revealing selective enhancement (asterisk) within the islets (dotted line) and the linear density (possibly a communicating vessel) (arrows). (c) Following MRI, the kidney (circle) was exposed in vivo and a low power photomicrograph was taken of the transplanted islets (dotted line). Note the blood vessels on the kidney surface near the transplant (a, b, and c are from the same kidney).

Figure 3. Normalized dynamic contrast-enhanced (DCE) magnetic resonance imaging gadolinium concentration curves at day 3 and 14

(a) At day 3, muscle and kidney contrast enhancement curves reached a peak in about 22 min, and a plateau by 30 min after contrast injection. Day 3 islet enhancement curve peak occurred at 21 min after injection. At day 14, islet curve peak is within 9 min of injection with a slow decline to similar levels as muscle and kidney by 30 min. (b) Area under the curve represents the relative amount of tissue contrast present during the 30-min DCE experiment. At day 3, all the tissues of interest had similar areas under the curve. At day 14, there was a significant increase in the area under the curve for islets compared to day 3. *P < 0.05.