ORGAN REJECTION DETECTION

器官排斥检测

• 批准号: 6121735
• 负责人: CHIEN HO
• 金额: $ 11.65万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121735
• 关键词: Mammalia; biomedical resource; cardiovascular system; human tissue; immunology; inflammation; magnetic resonance imaging; technology /technique; transplantation; urinary tract

The objectives of this research project are: (i) development of experimental rat kidney and rat heart transplantation models; (ii) development and application of non-invasive MRI techniques to monitor organ functions in these rat models during transplant rejection; (iii) comparison of MRI results with conventional invasive techniques. Renal function in transplanted organs was assessed by the MRI measurement of renal cortical perfusion using arterial spin tagging. Quantitative measurement of renal cortical perfusion detects changes in renal function associated with surgical stress as well as acute rejection. At 3 days post-transplantation, perfusion of the transplanted kidney's cortex was similarly reduced in both syngeneic and allogeneic transplant groups. At 7 days after transplantation, cortical perfusion was at the level of background noise in the allogeneic transplant group, and was significantly lower than the non-transplanted group or the syngeneic group at the same time point, indicating that quantitative MRI can easily detect severe rejection. Cardiac function after transplantation is investigated in three models: (i) ex-vivo isolated rat heart model assessed by Langendorff perfusion; (ii) in-situ isovolumic working heart model with implanted intraventricular balloon catheter; (iii) working left heart model assesed by MRI imaging. The heterotopic rat heart transplant system is used to characterize early changes in diastolic cardiac function indicative of diminished ventricular compliance in these studies. The sensitivity of the diastolic function indices, particularly the time constant of isovolumic relaxation, t, also permits a detailed evaluation of novel immunomodulatory strategies aimed at rapid reversal of the early rejection process. Using the in-situ balloon model, left ventricular pressure-volume relationships are determined. The potential drawback of this model is the possibility for thrombus formation in the left ventricular cavity, fibrosis of endocardium, and the loss of cardiac distensibility. The working left heart model solves these problems and MRI allows non-invasive, quantitation of ventricular function. :

该研究项目的目标是：（一）开发 实验大鼠肾脏和大鼠心脏移植模型;（ii） 无创MRI技术的发展和应用 在移植排斥期间这些大鼠模型中的器官功能;（iii） MRI结果与常规侵入性技术的比较。 通过MRI评估移植器官的肾功能 使用动脉自旋标记测量肾皮质灌注。 定量测量肾皮质灌注检测变化 在与手术应激相关的肾功能以及急性 排斥反应 在移植后3天， 移植肾的皮质在两个同基因组中同样减少， 和同种异体移植组。 移植后7天， 皮质灌注处于背景噪声水平， 异基因移植组，并显着低于 非移植组或同基因组在同一时间点， 表明定量MRI可以容易地检测严重排斥反应。 移植后的心脏功能研究在三个 模型：（i）通过Langendorff评估的离体分离的大鼠心脏模型 灌注;（ii）原位等容工作心脏模型， 心室内球囊导管;（iii）工作左心模型 通过MRI成像评估。 大鼠异位心脏移植系统 用于表征舒张期心脏功能的早期变化 表明这些研究中心室顺应性降低。 的 舒张功能指标的敏感性，特别是时间 等容松弛常数t也允许详细的 评价新的免疫调节策略， 逆转早期的排斥过程。 使用原位球囊 模型，确定左心室压力-容积关系。 该模型的潜在缺点是血栓的可能性 左心室腔内形成，内膜纤维化， 心脏扩张性的丧失。 工作的左心模型 解决了这些问题，MRI允许非侵入性，定量 心室功能 :