A novel approach with magnetic resonance imaging used for the detection of lung allograft rejection.
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.
Kanno
S
S
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
Lee
P C
PC
Dodd
S J
SJ
Williams
M
M
Griffith
B P
BP
Ho
C
C
D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D003911:Dextrans; D052203:Ferrosoferric Oxide; D006084:Graft Rejection / Q000175:diagnosis* / Q000473:pathology; D016041:Heart-Lung Transplantation; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007501:Iron / Q000008:administration & dosage; D008264:Macrophages; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D008854:Microscopy, Electron; D010087:Oxides / Q000008:administration & dosage; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D018709:Statistics, Nonparametric
D003287:Contrast Media; D003911:Dextrans; D007166:Immunosuppressive Agents; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide