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，从而可以阐明它们在涉及心血管系统发育、功能和控制的基本机制中的作用。大多数这种遗传学研究都是在老鼠身上进行的，因为基因改变相对容易，这反过来又产生了对能够检测非常小动物的表型变化的仪器的需求。我们一直积极参与这项工作，并开发和采用了许多有创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盈速度，以提供收缩和舒张期功能指数，以及使用核成像方法测量左、右室射血分数。目前，我们实验室还没有一种方法可以在多个维度上对心脏进行成像，并量化绝对的心室容量。这项提议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，以便能够实时成像小鼠的心脏运动和动力学。收购这台仪器将扩大我们的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)的发展和药理和/或外科操作的改变而跟踪心脏体积和功能的变化。其目标是能够量化收缩末期和舒张期末期心腔容量、总心肌体积以及心脏适应模型所产生的生理变化时的局部室壁厚度和运动。其他实验室已经使用超声心动图研究老鼠，并取得了越来越好的成功，这项技术已经进步到可以从老鼠身上获得可靠和可量化的图像的程度。我们已经确定了12名研究人员，他们由NIH的14项拨款资助，分为11个主要项目，涉及小鼠的遗传和其他建模，他们将从使用这种设备中受益。最直接的好处将是评估心肌缺血、心脏肥厚、心力衰竭和衰老的模型，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.