title: 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, 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.
authors.affiliation: Department of Radiology, Focused Ultrasound Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.|Renal Division and Biomedical Engineering Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Transplantation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: S
authors.initials: S
authors.lastname: Ohori
authors.affiliation: Department of Radiology, Focused Ultrasound Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: F C
authors.initials: FC
authors.lastname: Meral
authors.affiliation: Transplantation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Uehara
authors.affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: S
authors.initials: S
authors.lastname: Giannini
authors.affiliation: Renal Division and Biomedical Engineering Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: T
authors.initials: T
authors.lastname: Ichimura
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: R N
authors.initials: RN
authors.lastname: Smith
authors.affiliation: Department of Radiology, Focused Ultrasound Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: F A
authors.initials: FA
authors.lastname: Jolesz
authors.affiliation: Renal Division and Biomedical Engineering Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: I
authors.initials: I
authors.lastname: Guleria
authors.affiliation: Department of Radiology, Focused Ultrasound Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Focused Ultrasound Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: P J
authors.initials: PJ
authors.lastname: White
authors.affiliation: Department of Radiology, Focused Ultrasound Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: N J
authors.initials: NJ
authors.lastname: McDannold
authors.affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: K
authors.initials: K
authors.lastname: Hoffmeister
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: M M
authors.initials: MM
authors.lastname: Givertz
authors.affiliation: Transplantation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: R
authors.initials: R
authors.lastname: Abdi
mesh_terms: D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology; D016027:Heart Transplantation / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous; D014463:Ultrasonography / Q000379:methods*
chemical_list: D003287:Contrast Media
keywords: animal models: murine; basic (laboratory) research/science; organ transplantation in general; rejection