Magnetic resonance imaging detection of rat renal transplant rejection by monitoring macrophage infiltration.
BACKGROUND
A rat renal transplantation model was studied by noninvasive magnetic resonance imaging (MRI) with an infusion of ultrasmall superparamagnetic iron oxide (USPIO) particles to test whether the accumulation of immune cells, such as macrophages, could be detected in vivo while the kidney transplant was being rejected.


METHODS
Major histocompatibility disparate DA to BN male rat renal transplantation recipients were infused with USPIO particles, with magnetic resonance (MR) images acquired before, immediately after, and one day following infusion.


RESULTS
When the USPIO infusion was on the fourth day post-transplantation, some rejecting allografts showed a decrease of MR signal intensity one day later. Isografts and allografts with triple immunosuppressant treatment had 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. Morphological studies by electron microscopy confirmed the existence of iron inside the lysosomes of macrophages of rejecting kidneys, while Prussian blue staining 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 infusion with pathological manifestation in a rat renal allograft model suggests the possibility that renal transplantation status may be assessed by MRI using USPIO particles as markers for the accumulation of immune cells, such as macrophages.
Zhang
Y
Y
Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pennsylvania, USA.
Dodd
S J
SJ
Hendrich
K S
KS
Williams
M
M
Ho
C
C
D000818:Animals; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D004396:Coloring Agents; D005290:Ferric Compounds / Q000032:analysis / Q000737:chemistry; D005295:Ferrocyanides; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology*; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008247:Lysosomes / Q000737:chemistry / Q000648:ultrastructure; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D010316:Particle Size; D051381:Rats; D011914:Rats, Inbred BN; D014184:Transplantation, Homologous
D015415:Biomarkers; D004396:Coloring Agents; D005290:Ferric Compounds; D005295:Ferrocyanides; C000499:ferric oxide; C000170:ferric ferrocyanide