Noninvasive real-time intracardiac pressure measurements using subharmonic ultrasound

 描述(由申请人提供)：超声心动图技术用于评估心脏功能，由于不能无创地持续测量心内压而受到限制。如果我们能够确定对比剂微泡的辐射及其亚谐振荡可以准确和连续地测量心内压，超声心动图的许多物理局限性将被克服。我们的团队已经证明，微泡超声造影剂产生的非线性亚谐信号分量可以很好地指示流体静压变化(从0到200毫米汞柱)。在此基础上，提出并研究了一种亚谐辅助压力估计(SHAPE)方法。Shape通过在一个频率上传输来估计内部压力的变化，但仅在亚谐频率上测量信号响应。这项技术有可能无创地测量压力的变化，并已在动物身上得到验证。我们正在进行的可行性研究为SHAPE在人类身上提供了概念验证。该项目的基本假设是，计划进行左心和/或右心导管术的患者的心内压变化可以使用SHAPE实时测量，结果将与基于导管的压力测量结果相媲美。因此，有关心血管系统功能完整性的基本信息可以实时无创地提供，这将从根本上改变这类患者的临床管理。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，用于实时SHAPE压力测量，这将在体外进行验证(特定目标1)。接下来，我们将使用SHAPE研究计划进行左心和/或右心导管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相关联，并确定使用SHAPE进行压力测量的误差是否在基于导管的压力数据的5 mm Hg以内(特定目标2)。最后，对于一组临床提示行左心导管术的患者，除了使用SHAPE和高保真微型压力计导管(Mikro-Cath，Millar，Inc.，Houston，TX)(特定目标3)，我们还将比较心室松弛速率(峰值等容-dp/dt)和松弛时间常数(tau或τ)，以及使用SHAPE和高保真微压计头导管(Mikro-Cath，Millar，Inc.，Houston，TX)获得的临床重要的心室收缩和舒张压。总之，这项研究的目的是在最先进的商业超声扫描仪上提供一种改进的、临床上有用的创新SHAPE算法的实时实施，并通过非侵入性地评估人体的心内压来挑战侵入性确定的、对计划进行心导管手术的患者进行压力测量的临床范例。

 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.