PHYSIOLOGICAL MECHANISMS OF MYOCARDIAL FORCE GENERATION

心肌力量产生的生理机制

• 批准号: 8363179
• 负责人: PANOS P CONSTANTINIDES
• 金额: $ 1.23万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363179
• 关键词: Agriculture; Anesthesia procedures; Animal Experimentation; Cardiac; Cyprus; Development; Dose; Ethics; European; Female; Funding; Generations; Genetic; Gills; Grant; Heart; Housing; IACUC; Image; Institutes; Licensing; Lung; Magnetic Resonance Imaging; Maps; Mechanics; Microscopy; Mus; Myocardial; National Center for Research Resources; Neurology; Perfusion; Phase; Physiologic pulse; Physiological; Poaceae; Principal Investigator; Protocols documentation; Radial; Research; Research Infrastructure; Resources; Rodent; Slide; Source; Testing; The Jackson Laboratory; United States National Institutes of Health; Universities; Validation; Work; base; cost; male; radiofrequency; reconstruction; research study; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. AIM: Global mechanical function and perfusion of the mouse heart can be accurately and precisely characterized with strain tensor phase mapping with Displacement Encoding with Stimulated Echoes and radial projection imaging, under optimal anesthesia types and doses, using MRI. WORK PACKAGES -- Development and Testing of Radiofrequency (RF) coils for Cardiac MRI studies. -- Development of a DENSE pulse sequence for cardiac functional mouse studies. -- Development of a comprehensive cardiac function for high-throughput acquisitions in normal mice under anesthesia using MRI. METHODOLOGY: For MRI studies, pulse sequences, imaging protocols and hardware tests, will be validated with simulations and in experiments using phantoms and mice at CIVM-Duke 290 normal mice (male and female, CB57L, CD-1, and FVB strains, weightH20-30g) will be used for the studies of [WP 3-4, 5-8], at LBI and CIVM. For the LBI studies, mice will be purchased from the Cyprus Institute of Neurology and Genetics or from The Jackson Laboratory, USA. Additional mice will be ordered and used at CIVM for testing and validation of the proposed cardiac MRI studies. All studies will be performed in accordance with the rules of ethical conduct of research at Duke University and the Institutional Animal Care and Use Committee, and in accordance with national rules set by the Ministry of Agriculture in Cyprus and according to the European Animal Research directives. The project coordinator and the LBI are fully licensed by the Ministry of Agriculture in Cyprus to conduct the proposed experimental work with mice Pulse Sequence Development and Testing: The 7.0 Tesla scanner (on an Excite GE operating console) will be used for implementation, simulation, and testing of hardware (birdcage transmit [TX]/receive [RX] coil, and RX phased array) and the DENSE/perfusion pulse sequences. A DENSE sequence will be implemented in-house, and tested on the simulator, and on stationary phantoms, and mice. A dynamic contrast enhanced MRI perfusion pulse sequence, previously implemented for pulmonary perfusion in rodents at CIVM, will be modified for use in cardiac mice studies. The sequence is based on interleaved radial imaging and a 'sliding window keyhole reconstruction'. Other commercially available pulse sequences will be tested and optimized for mouse cardiac functional studies, including Radial, Carr Purcell Meiboom Gill (CPMG), Spoiled Grass [SPGR], and FLASH type sequences.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目的：在最佳麻醉类型和剂量下，使用MRI，可以通过具有刺激回波位移编码的应变张量相位映射和径向投影成像准确和精确地表征小鼠心脏的整体机械功能和灌注。 工作包 --开发和测试用于心脏MRI研究的射频线圈。 --开发用于小鼠心脏功能研究的DENSE脉冲序列。 --在麻醉下使用MRI在正常小鼠中开发用于高通量采集的综合心脏功能。 研究方法：对于MRI研究，脉冲序列、成像协议和硬件测试将通过模拟和在CIVM-Duke使用体模和小鼠的实验进行验证 290只正常小鼠（雄性和雌性，CB 57 L、CD-1和FVB品系，体重H20 - 30 g）将用于LBI和CIVM的[WP 3-4，5-8]研究。对于LBI研究，小鼠将购自Cyprus Institute of Neurology and Genetics或美国杰克逊实验室。将订购额外的小鼠，并在CIVM用于测试和确认拟定的心脏MRI研究。所有研究将按照杜克大学和机构动物护理和使用委员会的研究伦理行为规则，并按照塞浦路斯农业部制定的国家规则和欧洲动物研究指令进行。项目协调员和LBI完全获得塞浦路斯农业部的许可，可以进行拟议的小鼠实验工作 脉冲序列开发和测试：7.0 T扫描仪（在Excite GE操作控制台上）将用于硬件（鸟笼式发射[TX]/接收[RX]线圈和RX相控阵列）和DENSE/灌注脉冲序列的实施、模拟和测试。将在内部实施DENSE序列，并在模拟器、固定体模和小鼠上进行测试。将修改先前在CIVM中用于啮齿动物肺灌注的动态对比增强MRI灌注脉冲序列，以用于心脏小鼠研究。该序列是基于交错径向成像和“滑动窗口锁孔重建”。将针对小鼠心脏功能研究对其他市售脉冲序列进行测试和优化，包括Radial、卡尔珀塞尔Meiboom Gill（CPMG）、Spoiled Grass [SPGR]和FLASH型序列。