ECHOCARDIOGRAPHIC IMAGING SYSTEM FOR MICE

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During the last decade there has been an enormous increase in the application of genetic modelling in the study of the cardiovascular system. Genetic manipulations resulting in the absence or the overexpression of specific proteins allows the elucidation of their role in basic mechanisms involved in the development, function, and control of the cardiovascular system. Most of this genetic research is done in mice because of the relative ease in making alterations in the genotype, and this in turn has created a need for instrumentation capable of detecting phenotypical changes in very small animals. We have been active in this endeavor, and have developed and adapted many invasive and non invasive measurement devices, physiologic models and techniques to evaluate cardiovascular function in mice. We have concentrated on functional measurements and can now measure cardiac ejection and filling velocities using high frequency pulsed Doppler techniques to provide indices of systolic and diastolic function, and left and right ventricular ejection fractions using nuclear imaging methods. Presently we do not have a method in our laboratory which can image the heart in more than one dimension and quantify absolute ventricular volumes. The purpose of this proposal is to acquire an echocardiographic instrument with high spatial and temporal resolution to allow real-time imaging of cardiac motion and dynamics in mice. The acquisition of this instrument would expand the capabilities of our murine physiology laboratory and allow us to follow changes in cardiac volumes and function as the models (such as hypertrophy or failure) develop and are altered by pharmacologic and/or surgical manipulations. The goal is to be able to quantify end-systolic and end-diastolic chamber volume, total myocardial volume, and regional wall thickness and motion as the heart adapts to the physiologic alterations produced by the models. Other laboratories have used echocardiography to study mice with increasingly good success, and the technology has advanced to the point that reliable and quantifiable images can be obtained from mice. We have identified 12 investigators funded by 14 NIH grants divided into 11 major projects involving genetic and other modelling in mice which will benefit from using this device. The most direct benefit will be in evaluating models of myocardial ischemia, cardiac hypertrophy, heart failure, and aging which are known to affect the size and function of the heart.