Faculty Bibliography

Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron-oxide labeled immune-cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T 2*-weighted images. In this study, we tested the feasibility of using a fluorine-based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine-19 ((19) F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro-15-crown-5-ether, we observed (19) F-signal intensity in the organs experiencing rejection by (19) F MRI, and conventional (1) H MRI was used for anatomical context. Immunofluorescence and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, (19) F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients.

BACKGROUND:Long-term survival of heart transplants is hampered by chronic rejection (CR). Studies indicate the involvement of host macrophages in the development of CR; however, the precise role of these cells in CR is unclear. Thus, it is important to develop noninvasive techniques to serially monitor the movement and distribution of recipient macrophages in chronic cardiac allograft rejection in vivo. METHODS AND RESULTS/RESULTS:We have employed a rat heterotopic working-heart CR model for a magnetic resonance imaging experiment. Twenty-one allograft (PVG.1U-->PVG.R8) and 9 isograft (PVG.R8-->PVG.R8) transplantations were performed. Recipient macrophages are labeled via intravenous injection of micron-sized paramagnetic iron oxide particles (0.9 microm in diameter) at a dose of 4.5 mg Fe per rat 1 day before transplantation. Serial in vivo magnetic resonance images were acquired for up to 16 weeks. The migration of labeled recipient cells in our CR model, in which cardiac CR is evident at 3 weeks and most extensive by 16 weeks after transplantation, can be assessed with the use of in vivo magnetic resonance imaging for >100 days after a single micron-sized paramagnetic iron oxide injection. The location and distribution of labeled recipient cells were confirmed with magnetic resonance microscopy and histology. CONCLUSIONS:This approach may improve our understanding of the immune cells involved in CR and the management of heart transplantation. Moreover, this study demonstrates the feasibility of noninvasively observing individual targeted cells over long time periods by serial in vivo magnetic resonance imaging.