ECHOCARDIOGRAPHIC IMAGING SYSTEM FOR MICE

在过去的十年中，遗传模型在心血管系统研究中的应用有了巨大的增长。基因操作导致特定蛋白质的缺失或过度表达，从而阐明了它们在心血管系统发育、功能和控制的基本机制中的作用。大多数基因研究都是在老鼠身上进行的，因为改变基因型相对容易，这反过来又产生了对能够检测非常小的动物表型变化的仪器的需求。我们一直在这方面积极努力，并开发和适应了许多侵入性和非侵入性测量设备，生理模型和技术来评估小鼠的心血管功能。我们专注于功能测量，现在可以使用高频脉冲多普勒技术测量心脏射血和充血速度，以提供收缩和舒张功能指标，并使用核成像方法测量左心室和右心室射血分数。目前我们的实验室还没有一种方法可以对心脏进行多维成像并量化绝对心室容积。本提案的目的是获得一种具有高空间和时间分辨率的超声心动图仪器，以便实时成像小鼠的心脏运动和动力学。该仪器的获得将扩大我们小鼠生理学实验室的能力，并使我们能够随着模型（如肥大或衰竭）的发展和药物和/或手术操作的改变而跟踪心脏容量和功能的变化。目标是能够量化收缩末和舒张末心室容积、心肌总容积、区域壁厚和运动，因为心脏适应了模型产生的生理变化。其他实验室利用超声心动图对小鼠进行研究，取得了越来越好的成功，并且技术已经发展到可以从小鼠身上获得可靠的、可量化的图像。我们已经确定了由14项NIH拨款资助的12名研究人员，他们被分为11个主要项目，涉及小鼠的遗传和其他建模，他们将从使用该设备中受益。最直接的益处将是评估心肌缺血、心肌肥厚、心力衰竭和衰老模型，这些模型已知会影响心脏的大小和功能。

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.