ASSESSMENT OF MURINE CARDIAC FUNCTION USING MR IMAGING

使用 MR 成像评估小鼠心脏功能

• 批准号: 7726174
• 负责人: PANOS P CONSTANTINIDES
• 金额: $ 0.65万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726174
• 关键词: Address; Agonist; Anesthesia procedures; Animals; Area; Arts; Calcium; Cardiac; Cardiomyopathies; Cardiovascular Diseases; Cardiovascular system; Catheterization; Cell physiology; Computer Retrieval of Information on Scientific Projects Database; Cues; Cyprus; Development; Disease Management; Employment Opportunities; Europe; European; Funding; Gene Transfer Techniques; Generations; Genetic; Goals; Grant; Heart; Heart failure; Human; Image; Institution; Interdisciplinary Study; Intervention; Invasive; Knowledge; Lead; Magnetic Resonance Imaging; Mechanics; Mediating; Metabolism; Modeling; Molecular; Mus; Myocardial; Myocardial Contraction; Nature; Organ; Perfusion; Physiology; Property; Quality of life; Relaxation; Research; Research Personnel; Resources; Role; Services; Signal Transduction; Societies; Source; Structure; Techniques; Technology; Time; Tissue Engineering; Tissues; Training Programs; Transgenic Organisms; United States National Institutes of Health; Work; analog; bioimaging; cardiac depression; comparative; depressive symptoms; functional genomics; health care delivery; hemodynamics; improved; man; mouse model; multidisciplinary; novel; skills; tool development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project aims to elucidate mechanisms of myocardial force generation and relaxation in mice through (a) the study of the cardio-depressive effects of inhalational anesthesia at the cellular and tissue levels; (b) the hemodynamic assessment of global mechanical function using invasive catheterization techniques in normal states and with the use of inotropic agents, that include calcium analogs or intracellular agonists; and (c) non-invasive characterization of the murine cardiac function (strain tensor imaging) using Magnetic Resonance Imaging (MRI). All such aims will contribute in part to the complete characterization of the mouse model as a potentially useful model (structure-function, metabolism, perfusion) for extrapolation of scientific conclusions to man, and will ultimately allow comparative analyses of functional genomics in the mouse heart. Collectively, this project aims to develop the technological platform that will allow detailed studies of the cardiovascular system at the molecular, cellular, tissue and organ levels, addressing fundamental questions of the role of genetic cues in human cardiovascular disease, establishing at the same time the scientific platform for the development of a state-of-the-art animal imaging facility in Cyprus. In addition to the scientific value, the value for health care delivery and disease management, such a project will stimulate mobility efforts between USA, Europe and Cyprus and help attract investigators for the pursuit of such work, enable access opportunities to expertise and resources, and establish training programs polarised towards the transfer of knowledge from the USA to Europe and Cyprus, improving the skills and knowledge of European researchers. In all cases novel and superior products to existing ones, new employment opportunities in the high-technology sector would also offer a direct service to society, scientifically and through improvements in the value of the health care delivery and quality of life. The technical research and broader mobility and societal goals will be pursued through this proposed project, within the context of the analysis of the cardiodepressive effects of anesthesia on the animal physiology and myocardial contraction and relaxation, the study of global mechanical function and material properties of tissue at normal states and after positive inotropic intervention of calcium analogs or agonists. Technically, the project is targeted to address its objectives through the proposed research work in the elucidation of mechanisms of cardiac function and the application of pharmacological inotropic agents, as well as the direct use of the developed techniques in the study of mice with transgenic changes. Also, due to its multidisciplinary nature in physiology, cellular signalling, transgenesis, tissue engineering and bioimaging, multidisciplinary research efforts will be stimulated in the respective areas for the development of tools and techniques to study function, to analyse cellular mechanisms that mediate cardiodepression,, and to identify and study critical genetic foci that lead to prominent cardiomyopathies and heart failure.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究旨在通过（a）在细胞和组织水平上研究吸入麻醉对心脏的抑制作用;（B）在正常状态下使用有创导管技术对整体机械功能进行血流动力学评估，来阐明小鼠心肌力产生和舒张的机制 并使用包括钙类似物或细胞内激动剂的变力剂;和（c）使用磁共振成像（MRI）非侵入性表征鼠心脏功能（应变张量成像）。 所有这些目标将部分有助于小鼠模型作为一个潜在的有用的模型（结构-功能，代谢，灌注）外推到人的科学结论的完整表征，并最终允许在小鼠心脏的功能基因组学的比较分析。总体而言，该项目旨在 开发技术平台，以便在分子、细胞、组织和器官层面对心血管系统进行详细研究，解决遗传因素在人类心血管疾病中的作用这一基本问题，同时为在塞浦路斯开发最先进的动物成像设施建立科学平台。除了科学价值，医疗保健提供和疾病管理的价值，这样一个项目将刺激美国，欧洲和塞浦路斯之间的流动性努力，并有助于吸引研究人员从事这项工作，使获得专业知识和资源的机会，并建立培训计划，将知识从美国转移到欧洲和塞浦路斯。提高欧洲研究人员的技能和知识。在所有情况下，高技术部门的新就业机会都是比现有产品更新颖和更上级的产品，也将通过科学和提高保健服务的价值和生活质量，为社会提供直接服务。 将通过该拟议项目，在分析麻醉对动物生理学和心肌收缩和舒张的心脏抑制作用，研究正常状态下和钙类似物或激动剂正性肌力干预后组织的整体机械功能和材料特性的背景下，进行技术研究和更广泛的流动性和社会目标。从技术上讲，该项目的目标是通过拟议的研究工作来实现其目标，阐明心脏功能的机制，应用药理学正性肌力药物，以及直接使用已开发的技术来研究转基因小鼠。此外，由于其在生理学、细胞信号传导、转基因、组织工程和生物成像方面的多学科性质， 这些领域分别用于开发工具和技术，以研究功能，分析介导心脏抑制的细胞机制，并确定和研究导致显著心肌病和心力衰竭的关键遗传灶。