Surgical Planning Laboratory - Brigham & Women's Hospital - Boston, Massachusetts USA - a teaching affiliate of Harvard Medical School

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Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation

Institution:
1Focused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2Renal Division and Biomedical Engineering Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
3Transplantation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
4Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
5Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
6Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Publisher:
Wiley
Publication Date:
Jul-2017
Journal:
Am J Transplant
Volume Number:
17
Issue Number:
7
Pages:
1791-1801
Citation:
Am J Transplant. 2017 Jul;17(7):1791-1801.
PubMed ID:
28009476
PMCID:
PMC5481513
Keywords:
animal models, murine, basic (laboratory) research/science, organ transplantation in general, rejection
Appears in Collections:
NCIGT, SPL
Sponsors:
P41 EB015898/EB/NIBIB NIH HHS/United States
R01 AI126596/AI/NIAID NIH HHS/United States
R25 CA089017/CA/NCI NIH HHS/United States
R56 AI123270/AI/NIAID NIH HHS/United States
Generated Citation:
Fischer K., Ohori S., Meral F.C., Uehara M., Giannini S., Ichimura T., Smith R.N., Jolesz F.A., Guleria I., Zhang Y., White P.J., McDannold N.J., Hoffmeister K., Givertz M.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 Jul;17(7):1791-1801. PMID: 28009476. PMCID: PMC5481513.
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One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular 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%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection 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 noninvasive 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.