ASSESSMENT OF MURINE CARDIAC FUNCTION USING MR IMAGING

使用 MR 成像评估小鼠心脏功能

• 批准号: 7956896
• 负责人: PANOS P CONSTANTINIDES
• 金额: $ 1.09万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956896
• 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; Knowledge; Lead; Magnetic Resonance Imaging; Mechanics; Mediating; Metabolism; Microscopy; 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目旨在通过以下方式阐明小鼠心肌力产生和松弛的机制：（a）在细胞和组织水平上研究吸入麻醉的心脏抑制作用； (b) 在正常状态下使用侵入性导管技术并使用正性肌力药物（包括钙类似物或细胞内激动剂）对整体机械功能进行血流动力学评估； (c) 使用磁共振成像 (MRI) 对小鼠心脏功能进行非侵入性表征（应变张量成像）。 所有这些目标都将部分有助于小鼠模型的完整表征，作为一种潜在有用的模型（结构功能、代谢、灌注），用于将科学结论外推到人类，并最终允许对小鼠心脏的功能基因组学进行比较分析。总的来说，该项目旨在开发一个技术平台，允许在分子、细胞、组织和器官水平上对心血管系统进行详细研究，解决遗传线索在人类心血管疾病中的作用的基本问题，同时建立用于在塞浦路斯开发最先进的动物成像设施的科学平台。除了科学价值、医疗保健服务和疾病管理的价值外，这样的项目还将刺激美国、欧洲和塞浦路斯之间的流动工作，并有助于吸引研究人员从事此类工作，提供获得专业知识和资源的机会，以及建立两极分化的培训计划，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，比现有产品新颖和优质的产品，高科技领域的新就业机会也将通过提高医疗保健服务的价值和生活质量，科学地为社会提供直接服务。通过该拟议项目，将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、研究组织的整体机械功能和材料特性的背景下，追求技术研究和更广泛的流动性和社会目标在正常状态下以及在钙类似物或激动剂的正性肌力干预后。从技术上讲，该项目旨在通过拟议的研究工作来阐明心脏功能的机制和药理正性肌力药物的应用，以及直接使用已开发的技术来研究转基因小鼠，以实现其目标。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，将在各个领域刺激多学科研究工作，以开发研究功能的工具和技术，分析介导心脏抑制的细胞机制，识别和研究导致显着心肌病和心力衰竭的关键遗传病灶。