A novel approach with magnetic resonance imaging used for the detection of lung allograft rejection

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 120; no. 5; pp. 923 - 934
• Main Authors: Kanno, Shinichi, Lee, Paul C., Dodd, Stephen J., Williams, Mangay, Griffith, Bartley P., Ho, Chien
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.11.2000; AATS/WTSA
• Subjects: Analysis of Variance; Animals; Contrast Media - administration & dosage; Dextrans; Ferrosoferric Oxide; Graft Rejection - diagnosis; Graft Rejection - pathology; Heart-Lung Transplantation; Immunohistochemistry; Immunosuppressive Agents - administration & dosage; Iron - administration & dosage; Macrophages; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Microscopy, Electron; Oxides - administration & dosage; Rats; Rats, Inbred BN; Rats, Inbred Strains; Statistics, Nonparametric
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1067/mtc.2000.110184

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. (J Thorac Cardiovasc Surg 2000;120:923-34)