Arterial Properties from Stimulated Acoustical Emission

描述（由申请人提供）：测量各向异性动脉壁粘弹性的简单而可靠的方法将有助于我们了解疾病进展。此外，它还可以帮助开发针对动脉壁新靶点的新药物治疗方案。由于动脉壁本身的复杂性，动脉壁材料特性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个部分组成的调查计划。具体目标 1 中描述的第一部分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，根据可测量的动脉壁对施加的辐射力的响应来估计各向异性和粘弹性材料特性。这部分研究涵盖了超声波束辐射应力的计算以及解决反演问题的两种方法，例如解析计算反演方法和迭代有限元反演方法。该计划的第二部分“目标 2”旨在对目标 1 中开发的方法进行基于实验室的验证。验证将在切除的动脉和管上进行。此外，还将确定材料特性对动脉各种成分（例如弹性蛋白和胶原蛋白）的依赖性。该目标与第三个组成部分（目标 3）齐头并进，即在生猪中实施已开发的方法。重点是在猪动脉中测试该方法，这些猪动脉具有由疾病（在本例中为诱发高血压）引起的广泛硬度。将在猪的动脉上进行组织形态计量学，并将其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，在目标 4 中，将对已经参与正在进行的临床研究的人类动脉的各向异性粘弹性模量进行测量。经典的动脉硬度测量（例如 PWV 和增强指数以及脉压）将与新系统测量的粘弹性动脉壁模量相关。在临床扫描仪中实施此处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，该便携式扫描仪可以添加到 NIH 资助的临床试验中，并且对正在进行的方案进行最小程度的修改并以最低的成本。成功完成这些研究将了解粘弹性动脉壁模量与研究人群中一系列临床属性的关系，从而形成有价值的临床超声工具。公共健康相关性：该计划的长期目标是使用我们新颖的振动测量方法以高精度和高精度无创测量动脉壁材料特性。由此产生的定量测量将适合临床应用和人群研究。这里提出的方法的优点是它们是无创且快速的，可以实时测量动脉特性；他们不需要估计跨壁压力；他们考虑到特性是动脉壁内频率和方向的函数这一事实。该计划的成功完成将产生一种新的非侵入性科学和临床工具，用于测量血管壁的粘弹性频率相关的各向异性剪切模量，其时间和空间分辨率高于目前可用的分辨率。

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.