QUANTITATIVE 3D ULTRASOUND IMAGING OF THE MURINE HEART

描述(由申请者提供)：小鼠已成为心血管研究的首选物种，研究心血管疾病的遗传机制。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”小鼠的可获得性，加上传统的药理学方法，使小鼠成为研究心血管疾病的独特而强大的物种。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，但其高成本、低时间分辨率和低吞吐量限制了其广泛应用的潜力。我们提出了一种超声方法，可以准确、低成本、快速和非侵入性地量化小动物的心脏左心室(LV)体积和功能。此外，它易于使用，只需要最少的鼠标准备和最短的扫描时间。空间分辨率足以计算重要的解剖和生理参数(腔体积、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团注后心肌视频强度的时间演变来评估小鼠左室血流灌注。该项目的具体目标是： 1)研制了一种专用的小鼠超声换能器阵列/扫描器对，其横向分辨率为200微米，轴向分辨率为100微米，帧速率为每秒100帧以上。据信，这可能是第一个专门针对小鼠心脏成像进行优化的相控阵换能器。2)基于AIM 1中的阵列，开发了一种专门用于小鼠心脏成像的体积(3D)超声扫描仪。利用采集的2D图像帧的位置信息，我们将进行内插，形成3D体积数据集。 3)扩展小鼠心脏扫描仪的功能和用途，包括先进的图像处理，自动检测左室边界的新方法，以及基于造影剂的灌注图像的定量分析。 4)以磁共振成像(MRI)为标准，利用超声体模进行体外和在体小鼠心肌梗死的验证研究。

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.