DEVELOPMENT OF MRI TO DETECT CARDIAC REJECTION

MRI 检测心脏排斥反应的进展

• 批准号: 7196270
• 负责人: CHIEN HO
• 金额: $ 60.63万
• 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 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7196270
• 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; Invasive; 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; Purpose; Rattus; Research; Site; Staging; T-Lymphocyte; Techniques; Therapeutic Intervention; Tissues; Transplant Recipients; Work; 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）： 拟议研究的最终目标是使用非侵入性成像方法来通过改善急性和慢性同种异体功能障碍的检测和治疗来改善移植患者的管理。 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.当发生器官排斥反应时，免疫细胞会积聚在拒绝的心脏上。 MRI对比剂，例如，可以通过吞噬/内吞作用将右旋脱氧的超小超副磁铁（USPIO）颗粒和其他颗粒掺入大鼠巨噬细胞和/或T细胞中。可以静脉内引入这些颗粒或标记的细胞，以监测接枝排斥位点的免疫细胞的积累。我们提出的研究的具体目的是：（i）改善现有的并开发新的细胞标记技术，以将合适的MRI对比剂掺入免疫细胞中； （ii）改善现有的并开发新的细胞和功能性MRI技术来检测体内急性和慢性心脏排斥； （iii）通过MRI监测免疫细胞在体内的拒绝心脏的积累，作为一种新的非侵入性方法，可检测急性和慢性排斥反应，并监测我们异源性心脏大鼠模型的急性和慢性抑制在体内的各个阶段的移植心脏的功能变化，而无需治疗干预； （iv）将移植心脏的细胞和功能性MRI测量与常规的组织病理学，免疫学和生化参数相关，以评估心脏排斥反应，以验证我们的方法，以验证我们的方法并将MRI标记的免疫细胞与心肌功能相关联。所提出的心脏MRI技术本质上是普遍的'，可用于监测患有其他心脏病的患者，例如炎症性心肌病。通过允许在基线和治疗干预时对受伤的组织进行成像，细胞和功能性MRI为临床医学提供了巨大的潜力。可以应用细胞迁移的MRI跟踪来监测任何类型的细胞的运输，以进行研究和临床目的。