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.

We have just started recruiting heart transplant patients. Our preliminary data suggest the feasibility of carrying such study in human.

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.

CITATION INFORMATION: Fisher K, Uehara M, Ohori S, Meral C, Giannini S, Ichimura T, Smith N, Jolesz F, Guleria I, Zhang Y, White P, McDannold N, Hoffmeister K, Givertz M, Abdi R. Testing the Efficacy of Contrast Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress