DEVELOPMENT OF MRI TO DETECT CARDIAC REJECTION

MRI 检测心脏排斥反应的进展

• 批准号: 7754078
• 负责人: CHIEN HO
• 金额: $ 59.26万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-16 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7754078
• 关键词: Acute; Allografting; Biochemical; Biopsy; Cardiac; Cardiomyopathies; Cells; Chronic; Clinical; Clinical Medicine; Contrast Media; Coronary; Detection; Development; Dextrans; Diagnosis; Endocytosis; Experimental Models; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Gold; Graft Rejection; Heart; Heart Diseases; Heart Transplantation; Image; Imaging Techniques; Immune; Immunologic Monitoring; Infiltration; Inflammation; Inflammatory; Label; Magnetic Resonance Imaging; Measurement; Mediating; Methodology; Methods; Modeling; Monitor; Morbidity - disease rate; Myocardial; Myocardial perfusion; Nature; Organ; Organ Transplantation; Patient Monitoring; Patients; Phagocytosis; Process; Rattus; Research; Site; Staging; T-Lymphocyte; Techniques; Therapeutic Intervention; Tissues; Transplant Recipients; Vascular Diseases; Work; allograft rejection; cell motility; cell type; dextran; diagnosis standard; heart allograft; improved; in vivo; injured; innovation; iron oxide; macrophage; mortality; particle; trafficking

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.

描述（由申请人提供）： 该研究的最终目标是使用非侵入性成像方法，通过改善急性和慢性同种异体移植功能障碍的检测和治疗来改善移植患者的管理。近期目标是利用大鼠同种异体移植模型开发细胞和功能磁共振成像（MRI）的非侵入性方法，以监测免疫细胞向移植心脏的浸润情况并监测移植心脏的功能，从而早期发现心脏移植后同种异体移植心肌排斥（AMR）和心脏同种异体移植血管病变（CAV）的迹象。当器官排斥发生时，免疫细胞会在排斥的心脏处积聚。 MRI 造影剂，例如葡聚糖包被的超小超顺磁性氧化铁 (USPIO) 颗粒等，可以通过吞噬作用/内吞作用掺入大鼠巨噬细胞和/或 T 细胞中。这些颗粒或标记的细胞可以通过静脉注射来监测移植排斥部位免疫细胞的积累。我们提出的研究的具体目标是：（i）改进现有的和开发新的细胞标记技术，将合适的 MRI 造影剂掺入免疫细胞中； (ii) 改进现有的并开发新的细胞和功能性 MRI 技术，用于检测体内急性和慢性心脏排斥反应； （iii）通过MRI监测体内排斥心脏中免疫细胞的积累，作为一种新的非侵入性方法来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各个阶段的功能变化在我们的异位工作心率大鼠模型中，有或没有治疗干预； (iv) 将移植心脏的细胞和功能 MRI 测量结果与传统的组织病理学、免疫学和生化参数相关联，以评估心脏排斥反应，以验证我们的方法并将 MRI 标记的免疫细胞的浸润与心肌功能相关联。所提出的心脏 MRI 技术本质上是通用的，并且可以应用于监测患有其他心脏疾病的患者，例如炎症性心肌病。通过在基线上对受伤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。细胞迁移的 MRI 跟踪可用于监测任何类型细胞的运输，以用于研究和临床目的。