The general goal of this project is to develop ultrason aboutc instrumentation, transducers, and techniques to evaluat about cardiovascular function in man and in animal models of human diseases. During the last two decades there has been a shift toward the use of smaller animals such as rats and mice in medical research because of cost and the availability of inbred and genetically engineered models. In this renewal the following specific aims are proposed: 1) Develop a multichannel, highfidelity Doppler spectrum analyzer and software to permit velocity waveforms to be measured at two or more sites simultaneously in mice with sufficient fidelity to allow calculations of spectra for impedance evaluation and the detection and evaluation of vorticity, and with sub-millisecond temporal resolution for evaluation of cardiac timing and arterial pulse wave velocity. 2) Develop a simple M-mode echocardiograph with high spatial and temporal resolution and with the ability to track two interfaces for generation of real-time diameter waveforms. The system would operate simultaneously with the existing pulsed Doppler system and would provide dynamic, time-coherent dimension signals to complement velocity, pressure, and ECG signals from mice. 3) Develop small, focussed, single-element transthoracic and transesophageal transducers for high-resolution Doppler and M-mode echocardiography at 10 and 20 MHz in mice. These would be used to improve spatial resolution and (from the esophageal approach) to permit hands-free monitoring of aortic and carotid velocity and/or cardiac dimensions. 4) Develop a tail-cuff pressure measurement system using a Doppler probe to sense tail artery flow so that both systolic and diastolic pressure could be measured noninvasively in intact mice. 5) Develop a method to measure viscosity in small (<50 Ill) samples of fresh whole blood using Doppler detection of self-generated acoustic streaming. 6) Apply the techniques and systems outlined above to evaluate detailed hemodynamics in murine models o human conditions including: atherosclerosis, myocardial ischemia, cardiac hypertrophy, hypertension, aging, polycythemia, and other cardiovascular disorders. The developed methods will allow measurement and evaluation oi? cardiac timing, blood flow velocity, arterial pulse wave velocity, arterial impedance spectra, fluid dynamies, blood viscosity;flow disturbances and vorticity, pressure-volume and pressure-diameter relations, and peripheral resistance. Some of these noninvasive methods will be simple and fast enough for screening large numbers of genetically-altered mice for cardiovascular abnormalities.
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