Magnetic resonance imaging detection of rat renal transplant rejection by monitoring macrophage infiltration

Background. A rat renal transplantation model was studied by noninvasive ma gnetic resonance imaging (MRI) with an infusion of ultrasmall superparamagn etic iron oxide (USPIO) particles to test whether the accumulation of immun e cells, such as macrophages, could be detected in vivo while the kidney tr ansplant was being rejected. Methods. Major histocompatibility disparate DA to BN male rat renal transpl antation recipients were infused with USPIO particles, with magnetic resona nce (MR) images acquired before, immediately after, and one day following i nfusion. Results. When the USPIO infusion was on the fourth day post-transplantation . some rejecting allografts showed a decrease of MR signal intensity one da y later. Isografts and allografts with triple immunosuppressant treatment h ad no MR signal reduction. Immunohistologic staining for ED1(+) macrophages and CD4(+) and CD8(+) T cells in allogeneic transplanted kidneys indicated the accumulation of these immune cells as acute rejection occurred. Morpho logical studies by electron microscopy confirmed the existence of iron insi de the lysosomes of macrophages of rejecting kidneys, while Prussian blue s taining detected the presence of iron plaques in macrophages. Isografts and allografts with a triple immunosuppressant treatment exhibited smaller MR signal reductions with minimal histologic changes. Conclusions. The concurrence of MR signal reduction following USPIO infusio n with pathological manifestation in a rat renal allograft model suggests t he possibility that renal transplantation status may be assessed by MRI usi ng USPIO particles as markers for the accumulation of immune cells, such as macrophages.