Our general goals have been to develop ultrasonic instrumentation, transducers, and techniques for evaluation of cardiovascular physiology and function in man and in animal models of human diseases;and conditions, and recently we have been directing our efforts toward applications in mice. The unifying theme is the development of enabling technology consisting of simple, noninvasive methods which can be used by investigators to follow cardiovascular responses longitudinally as models develop, mature, and respond to challenges, and to quickly screen large numbers of mice. In this renewal we propose the following specific aims: 1) Develop a multigate pulsed Doppler module for measuring blood velocity and/or vessel wall motion in peripheral (carotid) arteries of mice. 2) Develop a multichannel Doppler signal processor to acquire and process multiple velocity and dimension signals taken simultaneously. 3) Develop and validate algorithms for calculating arterial parameters from noninvasively acquired velocity and diamete signals. 4a) Use the new devices, signal processing, and algorithms, to study arterial wave propagation and reflections in several mutant models of cardiovascular conditions. 4b) Characterize the differential remodeling of right and left carotid arteries in mice with a transverse aortic constriction producing highly pulsatile (right) and nearly steady (left) pressure and flow in the same mouse. 5) Develop esophageal electrodes and methods for noninvasive atrial pacing to control heart rate in mice. The sensors, instrumentation, signal processing, and algorithms will permit noninvasive serial measurements to be made in normal and genetically engineered mice during growth, maturation, and development with the potential for rapid screening. When validated in mice, the general concepts may have diagnostic applications in man and could be incorporated in to a clinical ultrasound scanner.
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