PHYSIOLOGICAL MECHANISMS OF MYOCARDIAL FORCE GENERATION

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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. 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.