DEVELOPMENT OF MRI TO DETECT CARDIAC REJECTION

描述(由申请人提供)： 这项研究的最终目标是使用非侵入性成像方法，通过改善对急性和慢性移植物功能障碍的检测和治疗来改善对移植患者的管理。目前的目标是利用大鼠同种异体心脏移植模型，发展无创的细胞和功能磁共振成像(MRI)方法，监测免疫细胞在移植心脏中的渗透，监测移植心脏的功能，从而检测心脏移植后同种异体心肌排斥反应(AMR)和同种异体心脏血管病变(CAV)的早期迹象。当器官发生排斥反应时，免疫细胞在排斥的心脏积聚。磁共振造影剂，如葡聚糖包被的超小超顺磁性氧化铁(USPIO)颗粒等，可以通过吞噬/内吞作用进入大鼠巨噬细胞和/或T细胞。这些颗粒或标记细胞可以静脉注射，以监测移植排斥反应部位免疫细胞的聚集情况。我们建议的研究的具体目标是：(I)改进现有的细胞标记技术，以将合适的MRI造影剂引入免疫细胞；(Ii)改进并开发新的细胞和功能MRI技术，用于检测体内的急性和慢性心脏排斥反应；(Iii)通过MRI监测免疫细胞在体内排斥心脏的积聚，作为一种新的无创性方法，以检测急性和慢性排斥反应，并监测移植心脏在体内急性和慢性排斥反应的不同阶段的功能变化；以及(Iv)将移植心脏的细胞和功能MRI测量结果与用于评估心脏排斥反应的常规组织病理学、免疫学和生化参数相关联，以验证我们的方法，并将MRI标记的免疫细胞的渗透与心肌功能相关联。拟议的心脏MRI技术本质上是通用的，可用于监测其他心脏疾病的患者，例如炎症性心肌病。通过允许在基线上对受损组织进行成像并进行治疗干预，细胞和功能MRI为临床医学提供了巨大的潜力。MRI细胞迁移跟踪可用于监测任何类型细胞的运输，用于研究和临床目的。

DESCRIPTION (provided by applicant): The ultimate goal of the proposed research is to use non-invasive imaging methodology to improve the management of transplant patients by improving the detection and treatment of acute and chronic allograft dysfunction. The immediate objective is to use rat allograft models to develop non-invasive methods of cellular and functional magnetic resonance imaging (MRI) to monitor the infiltration of immune cells into the transplanted heart and to monitor the function of transplanted hearts, and thereby to detect early signs of allograft myocardial rejection (AMR) and cardiac allograft vasculopathy (CAV) following heart transplantation. When organ rejection occurs, immune cells accumulate at the rejecting heart. MRI contrast agents, e.g., dextran-coated ultra small superparamagnetic iron-oxide (USPIO) particles and others can be incorporated into rat macrophages and/or T-cells by phagocytosis/endocytosis. These particles or labeled cells can be introduced intravenously to monitor the accumulation of immune cells at the site of graft rejection. The specific aims of our proposed research are: (i) to improve existing and to develop new cell labeling techniques to incorporate suitable MRI contrast agents into immune cells; (ii) to improve existing and to develop new cellular and functional MRI techniques for detecting acute and chronic cardiac rejection in vivo; (iii) to monitor by MRI the accumulation of immune cells at the rejecting heart in vivo as a new non-invasive approach to detect acute and chronic rejection and to monitor functional changes of the transplanted heart during various stages of acute and chronic rejection in vivo in our heterotopic working heart rat models with and without therapeutic intervention; and (iv) to correlate the results derived from cellular and functional MRI measurements of transplanted hearts with conventional histopathological, immunological, and biochemical parameters for evaluating cardiac rejection in order to validate our methods and to correlate infiltration of MRI-labeled immune cells with myocardial function. The proposed cardiac MRI techniques are general in nature 'and can be applied to monitor patients with other cardiac disorders, e.g., inflammatory cardiomyopathies. By allowing imaging of injured tissues at baseline and with therapeutic intervention, cellular and functional MRI offers great potential for clinical medicine. MRI tracking of cell migration can be applied to monitor the trafficking of any type of cells for research and clinical purposes.