Murine cardiac vector-flow imaging with high-frequency 2D row-column CMUT arrays

项目总结/摘要 心血管疾病（CVD）占美国每年死亡人数的三分之一。 部分心血管疾病患者发生心肌功能障碍。成像工具，允许早期 异常血液动力学和/或力学的检测提供了启动靶向治疗的机会 减少疾病的负担。小鼠是转化性CVD研究中最常见的模式生物 哺乳动物的心脏。超声（US）现在广泛用于小动物以获得心脏功能 参数然而，先进的美国心内向量流成像技术正在为人类的发展提供牵引力。 人CVD，如心肌病，尚未转化为临床前使用，因此，限制了功能性心脏 可以从小鼠获得的参数。采用US矢量流方法同时重建 以亚毫秒的时间分辨率解决复杂的心内血流模式和心脏力学， 明显的结构和功能异常，将增加一个新的临床前工具，研究之间的相互作用 血液流变学、心脏力学和适应性。 本项目的目标是开发一种新型的，30 MHz，2D CMUT，行列（RC）高频超声 阵列和平面波矢量流成像方法，能够进行心内全帧亚毫秒图像捕获 在小鼠中成像。与标准线性阵列不同，2D CMUT阵列将允许动态、免提选择 最佳扫描平面和在正交图像平面中采集数据的能力。此外，CMUT 阵列将允许我们收集相邻平面中的数据，以提供小鼠体内血流动力学的3D视图 心为了验证我们的系统，并证明小动物成像的实用性，我们将研究心内左 心室（LV）血流模式在两个高度相关的小鼠品系，但显示不同的反应 （进行性肥大vs.扩张和衰竭）与由公认的 横主动脉缩窄（TAC）模型。我们假设我们的矢量流系统能够量化 与假手术对照小鼠相比，左心室血流模式异常，我们将能够检测到血流中断 在传统的功能性回声或应变测量改变之前。重要的是，我们还假设， 在疾病过程的早期就可以识别出艾德的血流模式特征， 注定要发展为进行性肥大而不是扩张的心脏。检测细微表型的能力 早期疾病或治疗导致的常见CVD小鼠模型的变化可能会转化为 更早和更积极地治疗压力超负荷诱发心力衰竭风险最高的患者。

Project Summary/Abstract Cardiovascular disease (CVD) accounts for one of every three deaths each year in the U.S. A substantial pro- portion of patients with cardiovascular disease develop myocardial dysfunction. Imaging tools that permit early detection of abnormal hemodynamics and/or mechanics provide an opportunity to initiate targeted therapeutics and diminish the burden of disease. Mice are the most common model organism for translational CVD studies of the mammalian heart. Ultrasound (US) is now extensively used in small animals to obtain cardiac functional parameters. However, advanced US intracardiac vector-flow imaging techniques that are gaining traction for hu- man CVD, such as cardiomyopathies, have yet to translate to preclinical use, thus, limiting the functional cardiac parameters that can be obtained from mice. The ability to employ US vector-flow methods to simultaneously re- solve complex, intracardiac blood flow patterns and cardiac mechanics at sub-millisec temporal resolution, prior to overt structural and functional abnormalities, would add a new preclinical tool to study the interplay between blood flow, cardiac mechanics and adaptation in CVD mouse models. The goal of this project is to develop a novel, 30-MHz, 2D CMUT, row-column (RC) high-frequency-ultrasound array and a plane-wave vector-flow imaging approach capable of sub-ms, full-frame image capture for intracardiac imaging in mice. Unlike a standard linear array, the 2D CMUT array will allow dynamic, hands-free selection of the optimal scan plane and the ability to acquire data in orthogonal image planes. In addition, the CMUT array will allow us to collect data in adjacent planes to provide a 3D view of flow dynamics within the murine heart. To validate our system and demonstrate the utility for small-animal imaging, we will study intracardiac left ventricle (LV) blood flow patterns in two highly related mouse strains that nonetheless display divergent responses (progressive hypertrophy vs. dilatation and failure) to abnormal pressure overload induced by the well-established model of transverse aortic constriction (TAC). We hypothesize that our vector-flow system will be able to quantify abnormal left ventricle flow patterns relative to sham control mice and that we will be able to detect flow disruption prior to changes in traditional functional echo or strain measures. Importantly, we also hypothesize that distinct flow pattern signatures can be identified early in the course of disease that will permit discrimination between hearts that are destined to develop progressive hypertrophy vs. dilation. The ability to detect subtle phenotypic changes in common mouse models of CVD that are a result of early-stage diseases or therapies may translate to earlier and more aggressive treatment of patients at highest risk of pressure-overload induced heart failure.