S Kanno1, P C Lee, S J Dodd, M Williams, B P Griffith, C Ho. 1. Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, and the Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA. chienho@andrew.cmu.edu
Abstract
OBJECTIVE: Although various techniques have been explored for the detection and quantification of allograft transplant rejection, a practical and reliable method that is noninvasive is still elusive. METHODS: For our magnetic resonance imaging experiments, we have developed a new rat model of heterotopic lung transplantation to the inguinal region. Allogeneic transplants (DA to Brown Norway) were performed with and without cyclosporine A (INN: ciclosporin) treatment, with syngeneic transplants (Brown Norway to Brown Norway) serving as controls (n = 6 per group). Magnetic resonance images were obtained with a gradient echo method before and after injection of ultra-small superparamagnetic iron oxide particles. RESULTS: At day 5, allogeneic transplants without cyclosporine A treatment showed a grade 4 rejection histologically. A significantly lower magnetic resonance signal was seen 24 hours after injection of ultra-small superparamagnetic iron oxide particles compared with the preinjection image (346 +/- 7.6 vs 839 +/- 43.4 arbitrary units; P <. 05). Syngeneic transplants showed no evidence of rejection histologically and no differences in magnetic resonance imaging signals between the images before and after injection of ultra-small superparamagnetic iron oxide particles (863 +/- 18.8 vs 880 +/- 22.5). Allotransplants treated with cyclosporine A showed a grade 2 rejection histologically. The change in magnetic resonance signals in that group was small but showed a significant decrease in signal intensity after injection (646 +/- 10.5 vs 889 +/- 23.5, P <.05). Immunohistochemistry and iron staining of the allografts indicated that ultra-small superparamagnetic iron oxide particles were taken up by the infiltrating macrophages that accumulated at the rejection site. CONCLUSIONS: We have demonstrated a novel approach for the detection of acute lung allograft rejection using magnetic resonance imaging coupled with injection of ultra-small superparamagnetic iron oxide particles. Despite its limitations, our method might be a first step toward a potential clinical application.
OBJECTIVE: Although various techniques have been explored for the detection and quantification of allograft transplant rejection, a practical and reliable method that is noninvasive is still elusive. METHODS: For our magnetic resonance imaging experiments, we have developed a new rat model of heterotopic lung transplantation to the inguinal region. Allogeneic transplants (DA to Brown Norway) were performed with and without cyclosporine A (INN: ciclosporin) treatment, with syngeneic transplants (Brown Norway to Brown Norway) serving as controls (n = 6 per group). Magnetic resonance images were obtained with a gradient echo method before and after injection of ultra-small superparamagnetic iron oxide particles. RESULTS: At day 5, allogeneic transplants without cyclosporine A treatment showed a grade 4 rejection histologically. A significantly lower magnetic resonance signal was seen 24 hours after injection of ultra-small superparamagnetic iron oxide particles compared with the preinjection image (346 +/- 7.6 vs 839 +/- 43.4 arbitrary units; P <. 05). Syngeneic transplants showed no evidence of rejection histologically and no differences in magnetic resonance imaging signals between the images before and after injection of ultra-small superparamagnetic iron oxide particles (863 +/- 18.8 vs 880 +/- 22.5). Allotransplants treated with cyclosporine A showed a grade 2 rejection histologically. The change in magnetic resonance signals in that group was small but showed a significant decrease in signal intensity after injection (646 +/- 10.5 vs 889 +/- 23.5, P <.05). Immunohistochemistry and iron staining of the allografts indicated that ultra-small superparamagnetic iron oxide particles were taken up by the infiltrating macrophages that accumulated at the rejection site. CONCLUSIONS: We have demonstrated a novel approach for the detection of acute lung allograft rejection using magnetic resonance imaging coupled with injection of ultra-small superparamagnetic iron oxide particles. Despite its limitations, our method might be a first step toward a potential clinical application.
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