DOPPLER INSTRUMENTATION FOR VASCULAR PHYSIOLOGY IN MICE

DESCRIPTION (provided by applicant): Mice are now the primary model for determining the function of proteins expressed by specific genes many of which have cardiac and vascular implications. While the mouse cardiovascular system is similar to that of man in many respects, the limitations as a model of the human cardiovascular system are largely unknown because there are few suitable devices and techniques for making serial vascular measurements in mice. Our overall goal is to develop an ultrasound-based Mouse Vascular Research System (MVRS) that can be used to characterize vascular physiology in mice. Measurement capabilities will include blood velocities and vessel wall displacements from which we can determine and calculate diameter, volume, pressure, impedance spectra, segmental pulse wave velocity, characteristic impedance, forward and backward waves, and reflection coefficients. The MVRS will thus facilitate sophisticated analysis of vascular mechanics and will also allow simple and rapid screening for arterial abnormalities. We will use our commercially successful Doppler Signal Processing Workstation for mice (developed with prior SBIR funding) as a starting point to address the following specific aims during phase I: 1) Develop a 20 MHz ultrasound Doppler tissue displacement detector for vascular wall motion detection with 1/2 micron resolution; 2) Develop a dual gate, single probe 20 MHz ultrasound pulsed Doppler displacement detector for simultaneous acquisition of near and far arterial wall displacement signals; 3) Develop a dual channel pulsed Doppler velocimeter for simultaneous velocity monitoring at two adjacent locations to compute pulse wave velocity and arterial volume waves; and 4) Show feasibility of non-invasively measuring multiple Doppler signals simultaneously from peripheral vessels in mice with high spatial and temporal resolution. During Phase II we will refine the dual channel, dual gate pulsed Doppler system; develop comprehensive software for data acquisition, real time analysis, report generation, and user interface; and perform extensive in vivo validation in mice. Though our primary focus is on cardiovascular physiology, we will also add M-Mode imaging to assist in probe positioning and Doppler gate setting. The result will be a cost-effective commercial product that will act as an enabling technology for advancing the use of mice as models of human cardiovascular diseases and conditions.