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 where high spatial and temporal resolutions are critical. 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 multichannel, multigate, multifrequency DC coupled pulsed Doppler mainframe and modules for measuring blood velocity and/or tissue motion in central (heart and aorta) and peripheral (carotid and coronary) arteries of mice. 2) Develop and optimize signal processing to acquire, process, display, and generate waveforms and indices from multiple velocity and dimension signals taken simultaneously. 3) Perfect a dual-velocity method to assess segmental arterial volume pulsations. 4) Use velocity and diameter signals to characterize arterial wave propagation, mechanics, and reflections. 5) Study coronary flow velocity waveforms and reserve and validate the use of isoflurane as a coronary vasodilator in several mouse models. 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, many of the general concepts may have diagnostic applications in man and could be incorporated into clinical ultrasound scanners.
Mice are being used in medical research to study how genes control the structure and operation of the heart and blood vessel and how aging and human-like diseases affect their function. Because the mouse heart is the size of a small peanut and beats very fast, it is difficult to make images, to detect blockages in vessels, or to take detailed measurements of heart contraction and motion using standard methods. Our goal is to develop and improve high resolution ultrasonic sensors and devices to measure blood flow and motion in the very small hearts and blood vessels of mice used in medical research.
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|Crossland, Randy F; Durgan, David J; Lloyd, Eric E et al. (2013) A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries. Am J Physiol Regul Integr Comp Physiol 305:R334-42|
|Gurha, Priyatansh; Wang, Tiannan; Larimore, Ashley H et al. (2013) microRNA-22 promotes heart failure through coordinate suppression of PPAR/ERR-nuclear hormone receptor transcription. PLoS One 8:e75882|
|Quaini, A; Canic, S; Glowinski, R et al. (2012) Validation of a 3D computational fluid-structure interaction model simulating flow through an elastic aperture. J Biomech 45:310-8|
|Lloyd, Eric E; Crossland, Randy F; Phillips, Sharon C et al. (2011) Disruption of K(2P)6.1 produces vascular dysfunction and hypertension in mice. Hypertension 58:672-8|
|Cieslik, Katarzyna A; Taffet, George E; Carlson, Signe et al. (2011) Immune-inflammatory dysregulation modulates the incidence of progressive fibrosis and diastolic stiffness in the aging heart. J Mol Cell Cardiol 50:248-56|
|Hartley, Craig J; Reddy, Anilkumar K; Madala, Sridhar et al. (2011) Doppler velocity measurements from large and small arteries of mice. Am J Physiol Heart Circ Physiol 301:H269-78|
|Namiranian, Khodadad; Lloyd, Eric E; Crossland, Randy F et al. (2010) Cerebrovascular responses in mice deficient in the potassium channel, TREK-1. Am J Physiol Regul Integr Comp Physiol 299:R461-9|
|Hartley, Craig J; Reddy, Anilkumar K; Madala, Sridhar et al. (2010) Feasibility of dual Doppler velocity measurements to estimate volume pulsations of an arterial segment. Ultrasound Med Biol 36:1169-75|
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