Quantification of Islet Loss and Graft Functionality During Immune Rejection by 3-Tesla MRI in a Rat Model

Abstract

Because metabolic markers are not suitable for early diagnosis of islet graft dysfunction, magnetic resonance imaging (MRI) has been used to study islets that were labeled pretransplantation with superparamagnetic iron oxide nanoparticles. However, the relation between graft functionality assessed by glycemia, and MRI signal remains unclear. We transplanted hyperglycemic rats intraportally with 2500 ferucarbotran-labeled syngeneic (n=10) or allogeneic (n=12) islet equivalents or normoglycemic rats with 5000 xenogeneic human islet equivalents. Images were acquired on a clinical 3-Tesla MRI scanner. When rejection occurred on days 4 and 8 in xenogeneic and allogeneic recipients, 60% (57-68) and 55% (46-73) of the initial signal remained compared to 93% (71-104) and 82% (59-90) in syngeneic controls (P=0.006 and 0.03). With a cutoff value of 84% on day 4 for the diagnosis of allogeneic rejection, sensitivity of 91% and specificity of 70% were obtained. Based on MRI signal on day 4, treatment with antilymphocytic serum from day 4 allowed graft rescue in 75% of recipients. In this model, MRI of pretransplantation superparamagnetic iron oxide nanoparticle-labeled islet grafts allows timely diagnosis of immune rejection.