QUANTITATIVE 3D ULTRASOUND IMAGING OF THE MURINE HEART

描述（由申请人提供）：小鼠已成为心血管疾病遗传机制研究的首选物种。此外，小鼠越来越多地被用于研究对疾病和治疗的解剖和生理反应的演变。转基因和“基因敲除”小鼠的可用性，结合传统的药理学方法，使小鼠成为研究心血管疾病的独特强大物种。目前的一种非侵入性小鼠成像（MRI）方法具有良好的图像质量，但其广泛应用的潜力受到其高成本、低时间分辨率和低吞吐量的限制。我们提出了一种精确、低成本、快速和无创的小动物左心室（LV）容量和功能定量的超声方法。此外，它易于使用，需要最少的鼠标准备和最少的扫描时间。空间分辨率足以计算重要的解剖和生理参数（室容积、射血分数、心输出量等）。此外，我们利用优越的时间分辨率，通过分析微泡造影剂注射后心肌视频强度的时间演变来评估小鼠左室灌注。该项目的具体目标是：

DESCRIPTION (provided by applicant): The mouse has become the preferred species for cardiovascular research into the genetic mechanisms that underpin cardiovascular disease. In addition, mice are increasingly being used to study the evolution of anatomic and physiological responses to disease and therapy. The availability of transgenic and "knockout" mice, combined with conventional pharmacologic approaches, make the mouse a uniquely powerful species in which to study cardiovascular disease. One current method for non-invasive mouse imaging (MRI) has excellent image quality but its potential for widespread application is limited by its high cost, poor temporal resolution and low throughput. We propose an ultrasound method that provides accurate, low-cost, fast and non-invasive quantification of cardiac left ventricular (LV) volumes and function in small animals. Additionally, it is easy-to-use, requires minimal mouse preparation and minimal scanning time. The spatial resolution is sufficient to enable calculation of important anatomic and physiologic parameters (chamber volumes, ejection fraction, cardiac output, etc.) Furthermore, we take advantage of the superior temporal resolution to enable assessment of mouse LV perfusion using analysis of the time evolution of myocardial video intensity following bolus injection of microbubble contrast agents. The Specific Aims of this project are to: 1) Develop a dedicated murine ultrasound transducer array / scanner pair capable of a spatial resolution of 200 microns laterally and 100 microns axially with a frame rate of 100+ frames per second. It is believed that this may be the first phased array transducer optimized specifically for mouse heart imaging. 2) Develop a volumetric (3D) ultrasound scanner, specially matched for murine heart imaging, based on the array in Aim 1. Using positional knowledge of the acquired 2D image frames, we will interpolate to form a 3D volumetric data set. 3) Expand the capability and utility of the murine heart scanner to include advanced image processing, novel approaches to automatic LV border detection and include quantitative analysis of contrast agent-based perfusion images. 4) Perform a validation study in vitro using an ultrasound phantom and in vivo in infarcted mouse hearts using Magnetic Resonance Imaging (MRI) as a standard.