Testing the efficacy of Contrast Enhanced Ultrasound in detecting transplant rejection using a murine model of heart transplantation

Abstract One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, non-invasive and practical diagnostic tools to detect transplant rejection. Early intra-graft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in micro-vascular perfusion (MP) of cardiac transplants using Contrast Enhanced Ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, 92% on days 4, 6, and 8 post-transplantation, respectively) and chronic rejection (33%, 33%, 92% on days 5, 14, and 30 post-transplantation, respectively). Our perfusion studies showed restoration of MP following anti-rejection therapy, highlighting its potential to help monitor efficacy of anti-rejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for non-invasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection. This article is protected by copyright. All rights reserved.