Noninvasive real-time intracardiac pressure measurements using subharmonic ultrasound

 描述（由申请人提供）：用于评估心脏功能的超声心动图技术受到无法无创持续测量心内压的限制。如果我们能够确定造影剂微泡的超声作用及其亚谐波振荡分析可以准确和连续地测量心内压力，超声心动图的许多物理限制将被克服。我们的小组已经证明，来自基于微泡的超声造影剂的非线性生成的次谐波信号分量可以提供流体静压变化（从0到200 mmHg）的良好指示。在此基础上，提出并研究了一种称为次谐波辅助压力估计（SHAPE）的定量技术。SHAPE通过在一个频率下发射来估计内部压力变化，但仅在次谐波频率下测量信号响应。该技术具有非侵入性测量压力变化的潜力，并已在动物身上得到验证。我们正在进行的可行性研究为人类SHAPE提供了概念验证。该项目的基本假设是，计划进行左心和/或右心导管插入术的患者的心内压力变化可以使用SHAPE实时测量，并且结果将优于基于导管的压力测量。因此，关于心血管系统的功能完整性的基本信息可以实时地非侵入性地提供，这将从根本上改变此类患者的临床管理。最初，将在最先进的超声扫描仪（SonixTablet，Analogic Corporation，Peabody，MA）上实施包含最佳入射声压选择和次谐波信号处理的SHAPE算法，以进行实时SHAPE压力测量，并将在体外进行验证（具体目标1）。接下来，我们将研究计划使用SHAPE进行左心和/或右心导管插入术的患者的心脏压力变化，并将结果与基于导管的压力测量结果相关联，并确定使用SHAPE的压力测量误差是否在基于导管的压力数据的5 mmHg范围内（具体目标2）。最后，对于一组转诊进行临床指征左心导管插入术的患者，我们将比较心室舒张率（峰值等容-dP/dt）和舒张时间常数（tau或τ），以及使用SHAPE和高保真微压计尖端导管（Mikro-Cath，Millar，Inc.）获得的临床重要心室收缩压和舒张压。休斯顿，德克萨斯州）（具体目标3）。总之，本研究的目的是提供一种改进的和临床上有用的，实时实施的创新SHAPE算法的国家的最先进的，商业超声扫描仪和挑战的临床范例，有创确定，压力测量的患者安排心脏导管插入术的无创评估心内压力在人类。

 DESCRIPTION (provided by applicant): Echocardiographic techniques for the assessment of cardiac function have been limited by an inability to consistently measure intracardiac pressures noninvasively. If we can establish that insonation of contrast microbubbles and analysis of their subharmonic oscillations can accurately and continuously measure intracardiac pressures, many of the physical limitations of echocardiography would be overcome. Our group has demonstrated that the nonlinearly generated, subharmonic signal components from microbubble- based ultrasound contrast agents can provide an excellent indication of the hydrostatic pressure variation (from 0 to 200 mmHg). Based on these results, a quantitative technique called SubHarmonic-Aided Pressure Estimation (SHAPE) was proposed and investigated. SHAPE estimates internal pressure variations by transmitting at one frequency, but measuring signal response only at the subharmonic frequency. This technique has the potential to noninvasively measure changes in pressure and has been validated in animals. Our ongoing feasibility study provides proof-of-concept for SHAPE in humans. The fundamental hypothesis of this project is that intracardiac pressure changes in patients scheduled for a left and/or right heart catheterization can be measured using SHAPE in real-time and that results will compare favorably with catheter based pressure measurements. Thus, essential information regarding the functional integrity of the cardiovascular system can be provided noninvasively in real-time, which will fundamentally alter the clinical management of such patients. Initially, the SHAPE algorithm incorporating optimum incident acoustic pressure selection and processing of the subharmonic signals will be implemented on a state-of-the-art ultrasound scanner (SonixTablet, Analogic Corporation, Peabody, MA) for real-time SHAPE pressure measurements, which will be verified in vitro (Specific Aim 1). Next, we will study cardiac pressure changes in patients scheduled for a left and/or right heart catheterization using SHAPE and correlate results to catheter based pressure measurements and establish if the errors in pressure measurements using SHAPE are within 5 mmHg of the catheter-based pressure data (Specific Aim 2). Finally for a set of patients referred for clinically indicated left heart catheterization, we will compare the ventricular relaxation rate (peak isovolumic -dP/dt) and relaxation time constant (tau or τ) in addition to the clinically important ventricular systolic ad diastolic pressures obtained using SHAPE and high fidelity micromanometer-tipped catheters (Mikro-Cath, Millar, Inc. Houston, TX) (Specific Aim 3). In conclusion, this study aims to provide an improved and clinically useful, real-time implementation of the innovative SHAPE algorithm on a state-of- the-art, commercial ultrasound scanner and to challenge the clinical paradigm of invasively-determined, pressure measurements in patients scheduled for cardiac catheterization by noninvasively evaluating intracardiac pressures in humans.