Arterial Properties from Stimulated Acoustical Emission

描述（由申请人提供）：一种简单而可靠的测量动脉壁各向异性粘弹性的方法将有助于我们了解疾病的进展。此外，它还可以帮助开发针对动脉壁新靶点的新药物方案。由于动脉壁本身的复杂性，对其材料性质的估计是一个非常复杂的问题。为了解决这个问题，我们设计了一个由四部分组成的调查方案。第一部分，在具体目标1中描述，旨在完成数学和计算基础，这些基础将支持我们新开发的方法，通过可测量的动脉壁响应来估计材料的各向异性和粘弹性特性。这一部分的研究涵盖了超声光束辐射应力的计算和求解反问题的两种方法，即解析计算反方法和迭代有限元反方法。该计划的第二部分，Aim 2，旨在为Aim 1中开发的方法提供基于实验室的验证。验证将在切除的动脉和导管上进行。此外，还将确定材料性能对动脉中各种成分（如弹性蛋白和胶原蛋白）的依赖性。这个目标与第三个组成部分，目标3，在生猪中实施开发的方法密切相关。关键是要在猪动脉中测试这种方法，这些动脉由于疾病引起的僵硬程度很大，在这种情况下，是诱发高血压。将对猪的动脉进行组织形态学测量，并与测量的动脉壁粘弹性模量相关联。为了开始这些方法的临床应用，在Aim 4中，将测量已经参加正在进行的临床研究的人类动脉的各向异性粘弹性模量。传统的动脉刚度测量，如PWV和增强指数，以及脉压，将与新系统测量的动脉壁粘弹性模量相关联。在临床扫描仪中实施本文开发的方法将使我们能够使用便携式扫描仪对人体进行测量，这种扫描仪可以添加到NIH资助的临床试验中，对正在进行的方案进行最小的修改，成本最低。这些研究的成功完成将导致对研究人群中粘弹性动脉壁模量与一系列临床属性之间关系的了解，从而产生有价值的临床超声工具。公共卫生相关性：该项目的长期目标是使用我们新颖的振动测量方法，以高精度和精密度无创地测量动脉壁材料特性。由此产生的定量测量将适用于临床应用和人口研究。这里提出的方法的优点是它们是非侵入性和快速的，可以实时测量动脉特性；他们不需要估计跨壁压力；他们考虑到这些特性是动脉壁内频率和方向的函数。该计划的成功完成将产生一种新的无创科学和临床工具，用于测量血管壁黏弹性频率相关的各向异性剪切模量，具有比目前可用的更高的时间和空间分辨率。

DESCRIPTION (provided by applicant): A simple and robust method to measure anisotropic arterial wall viscoelasticity would help with our understanding of disease progression. Also, it can assist with developing new drug regimens addressing new targets in the arterial wall. Estimation of the material properties of the arterial wall is a very complex problem because of the complexity of the wall itself. To approach this problem, we have designed a four-component program of investigation. The first part, described in Specific Aim 1, is designed to complete the mathematical and computational foundations that will support our newly developed methods of estimating anisotropic and viscoelastic material properties from measurable arterial wall responses to applied radiation force. This part of the investigation covers computation of the radiation stress from the ultrasound beams and two approaches to solving the inverse problem e.g., an analytic computational inverse method and an iterative FEM inverse method. The second part of the program, Aim 2, is designed to give laboratory based validation of the methods developed in Aim 1. The validation will be conducted on excised arteries and tubes. In addition, the dependence of the material properties on various constituents of the artery such as elastin and collagen will be determined. This Aim goes hand in hand with the third component, Aim 3, implementation of the developed methods in live pigs. The point is to test the methods in pig arteries that have a wide range of stiffness induced by disease, in this case, induced hypertension. Histomorphometry will be done on the arteries of the pigs and correlated with the measured viscoelastic moduli of the arterial walls. To begin the clinical application of these methods, in Aim 4, measurements will be made of the anisotropic viscoelastic moduli of arteries in humans that are already enrolled in ongoing clinical studies. Classical arterial stiffness measurements such as PWV and augmentation index, and pulse pressure, will be correlated to the viscoelastic arterial wall moduli measured with the new system. Implementation in a clinical scanner of the methods developed here will allow us to make measurements in humans using a portable scanner that can be added to NIH funded clinical trials with minimal modification of the ongoing protocols and minimal cost. Successful completion of these studies will result in knowledge of the relationship of the viscoelastic arterial wall moduli to an array of clinical attributes in the studied populations resulting in a valuable clinical ultrasound tool. PUBLIC HEALTH RELEVANCE: The long-term goal of this program is to noninvasively measure arterial wall material properties with high accuracy and precision using our novel vibrometry methods. The resulting quantitative measures will be amenable to clinical applications and population studies. The advantages of the methods proposed here are that they are noninvasive and fast allowing real-time measurement of arterial properties; they do not need estimates of transmural pressure; and they take into account the fact that properties are a function of frequency and direction within the arterial wall. Successful completion of this program will result in a new noninvasive scientific and clinical tool for measuring the viscoelastic frequency dependent anisotropic shear moduli of the vessel wall with higher temporal and spatial resolution than currently available.