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.
Am J Transplant. 2017 Jul;17(7):1791-1801. doi: 10.1111/ajt.14180. Epub 2017 Feb 1.
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.
改善心脏移植长期预后的一个关键未满足需求是开发准确、无创和实用的诊断工具来检测移植排斥。在高级移植排斥之前，会发生早期移植物内炎症和内皮细胞损伤。我们开发了一种新的诊断成像平台，使用对比增强超声（CEUS）来检测心脏移植的微血管灌注（MP）的早期下降。CEUS 在检测移植排斥中的功效在心脏移植的小鼠模型中进行了测试，这是实体器官移植的标准临床前模型。与同基因组相比，在经历急性移植排斥的同种异体移植物中，MP 逐渐下降（移植后第 4、6 和 8 天分别为 40%、64%和 92%）和慢性排斥（移植后第 5、14 和 30 天分别为 33%、33%和 92%）。我们的灌注研究表明，在进行抗排斥治疗后 MP 得到了恢复，这突出了其监测抗排斥治疗效果的潜力。我们的数据表明，早期内皮细胞损伤和血小板聚集导致了同种异体移植物中观察到的早期 MP 下降。高分辨率 MP 映射可能允许非侵入性地检测心脏移植排斥。所呈现的数据有可能帮助开发用于诊断移植排斥的下一代成像方法。
