Abstract 3529: Early Detection of Transplant Rejection by in vivo 19F MRI
Introduction: Diagnosis of transplant rejection requires endomyocardial biopsy and entails risks. Here, we describe a new 19F MRI approach for detection of organ rejection making use of emulsified perfluorocarbons (PFCs) phagocytized by monocytes/macrophages to noninvasively visualize the macrophage host response.
Methods: Isografts from BL6 or allografts from BL10A mice were heterotopically transplanted into BL6 recipients followed by iv injection of PFCs (10% 15C5) at various times after surgery (n=6 each). In this model, allografts undergo predictable progressive rejection, leading to graft failure after 2–3 weeks.
Results: 1H/19F MRI enabled us to detect the initial immune response not later than 3 days after surgery. Anatomically matching example images obtained at 9.4 T at day 3 post allotransplantation are displayed below. 1H MRI shows the anatomy of the graft in the abdomen, and the corresponding 19F image matched a signal pattern in shape of the ventricular walls. Merging of these images confirms the localization of PFCs within the left and right ventricle. The observed 19F signal strongly increased with time reaching a persisting maximum after day 7 (n=6). Histology confirmed the presence of infiltrating monocytes/macrophages already at day 3 after allotransplantation. In contrast, isografts exhibited no detectable 19F signal at any time (n=6). In separate studies, this approach could also be applied to assess the success of rapamycin therapy after allotransplantation.
Conclusions: PFCs can serve as MRI contrast agent for the early and sensitive detection of transplant rejection, permitting an excellent degree of specificity due to lack of any 19F background.