LABORATORY INVESTIGATION TISSUE CHARACTERIZATION Magnetic resonance imaging of cardiac transplants: the evaluation of rejection of cardiac allografts with and without immunosuppression

The purpose of this study was to evaluate the potential of magnetic resonance imaging (MRI) in vivo for the characterization of tissue changes associated with acute myocardial rejection after cardiac transplantation. Of 15 dogs that underwent heterotopic cardiac transplantation, six served as untreated controls, and nine received immunosuppressive therapy (25 mg/kg/day cyclosporine, 1 mg/kg/day prednisone). Serial electrocardiographically gated MRI (spin-echo technique) and histologic examinations of allograft biopsy samples were performed for each dog at 2 to 3, 7 to 10, 14 to 17, and 26 to 29 days after transplantation and immediately after animals were killed. Untreated allografts showed a significant increase (p < .01) in T2 (spin-spin) relaxation time (T2 = 66 ± 8 msec) and intensity values compared with values in the native hearts (T2 = 44 + 6 msec) as early as 1 week after transplantation. The significant difference in T2 values could be observed in vivo as well as on postmortem examination and corresponded to histologic progression of the rejection process. There was no significant difference in TI, T2, or intensity values in cyclosporine-treated allografts and native hearts except in two dogs in which T2 relaxation times and signal intensity in the transplanted hearts increased simultaneously with histologic evidence of rejection, indicating failure of immunosuppressive therapy. There was a significant correlation between histologic grading of severity of rejection and T2 relaxation times of the cardiac transplants (r = .72). Likewise, there was a significant linear relationship between T2 values in vivo and percent water content when the differences between native hearts and allografts were compared (r = .92, p < .001). Thus, electrocardiographically gated MRI in vivo is a sensitive, noninvasive modality for detecting and estimating severity of acute rejection of cardiac transplants. Myocardial tissue characterization is possible by quantitating T2 relaxation times. Circulation 74, No. 1, 145-156, 1986. ENDOMYOCARDIAL BIOPSY is currently the standard technique used in the diagnosis of cardiac transplant rejection.'12 A noninvasive modality that would guide the timing of endomyocardial biopsy and assess the response to changes in immunosuppressive therapy would be advantageous. Excellent morphologic detail and tissue characterization have been obtained in pathologic studies of the myocardium with the use of magnetic resonance imaging (MRI).4 MRI has been found useful in the diagnosis of renal transplant rejecFrom the Departments of Radiology, Surgery, and Pathology, University of California Medical School, San Francisco, the Department of Radiology, First Medical Clinic, University of Vienna, and the Third Medical Clinic, University of Cologne. Address for correspondence: Charles B. Higgins, M.D., Department of Radiology, UCSF Medical Center, San Francisco, CA 94143. Received July 17, 1985; revision accepted March 27, 1986. Dr. Sechtem is supported by grant 411/11 from Deutsche Forschungsgemeinschaft. Dr. Tscholakoff is supported by NIH grant F05 TW03437, Fogarty International Center. Vol. 74, No. 1, July 1986 tion.5 In this regard, preliminary reports of magnetic resonance analysis of tissue samples in vitro have demonstrated Ti and T2 relaxation times to be prolonged in the presence of cardiac allograft rejection.6'7 The purposes of this study were: (1) to evaluate whether electrocardiographically (ECG) gated MRI can depict cardiac allograft rejection in untreated and cyclosporine-treated dogs with cardiac transplants, (2) to determine the time interval at which MRI in vivo can detect alterations in cardiac allografts undergoing rejection, and (3) to assess the correlation between histologic ratings or tissue water content and severity of rejection as quantitated by T2 relaxation times. Methods Experimental preparation and protocol. Fifteen unrelated beagles (8 to 10 kg) underwent heterotopic cardiac transplantation to the left hemithorax. After induction of anesthesia with pentobarbital (25 mg/kg) the dogs were intubated and anesthesia 145 by gest on A ril 4, 2017 http://ciajournals.org/ D ow nladed from