Measuring arterial material properties using wave-based approaches with ultrasound and computational models - Administrative Supplement

使用基于波的超声方法和计算模型测量动脉材料特性 - 行政补充

• 批准号: 10268369
• 负责人: James Fowler Greenleaf
• 金额: $ 8.98万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-17 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268369
• 关键词: Acoustics; Administrative Supplement; Algorithms; American; Arterial Fatty Streak; Arteries; Atherosclerosis; Beds; Behavior; Biological Markers; Blood Pressure; Blood Vessels; Cardiac; Cardiovascular Diseases; Carotid Arteries; Cause of Death; Clinical; Clinical assessments; Collagen; Complex; Computer Models; Deltastab; Deposition; Elasticity; Elastin; Elements; Event; Frequencies; Future; Goals; Intervention; Laboratories; Lead; Measurement; Measures; Medial; Methods; Minor; Modality; Modeling; Modernization; Modification; Motion; Organ; Pathologic; Patients; Population; Property; Radiation; Research; Resolution; Risk Factors; Structure; Techniques; Technology; Ultrasonography; United States; Variant; Vascular Diseases; Viscosity; Work; arterial stiffness; atherosclerotic plaque rupture; attenuation; base; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinical application; follow-up; human subject; improved; in vivo; instrument; mechanical properties; millisecond; programs; public health relevance; risk stratification; temporal measurement; vascular risk factor; viscoelasticity

Abstract Background: Cardiovascular disease (CVD) is the leading cause of death in the United States. It is estimated that 83.6 million Americans presently have at least one form of CVD and by 2030, 40.5% of the population will have some form of CVD, an increase of about 10% compared to 2010. Atherosclerosis, the main cause of CVD, is a systemic, pathologic condition characterized by several structural changes of the arteries. Increased arterial stiffness results primarily from increased collagen deposition and elastin fragmentation in the medial layer of the arterial wall and is recognized as an independent risk factor for adverse vascular events. Modifications of arterial structure lead to changes in arterial elasticity and viscosity, which have recently been found to predate clinical manifestations of occlusive atherosclerotic disease. Moreover, these changes tend to be widespread and are not limited to a single arterial bed and, as a consequence, contribute to target organ damage. These alterations in the artery are the culmination of known and unknown vascular risk factors that promote formation and progression of atherosclerotic lesions and may also increase the propensity for atherosclerotic plaque rupture. Our Goal is to develop a new class of arterial biomarkers based on the viscoelastic and nonlinear material properties of the vessel wall. These biomarkers could be used in the future for early assessment of subclinical abnormalities in the carotid artery by providing a widely available technology to detect ‘presymptomatic’ vascular disease to refine both CVD risk stratification and follow up for subsequent interventions. We will use acoustic radiation force (ARF) to generate propagating waves with high frequency bandwidth in the arterial wall. The wave motion will be analyzed with numerical dispersion methods, which we call arterial dispersion ultrasound vibrometry (ADUV). We use these ADUV wave propagation methods to quantitatively and noninvasively characterize the viscoelastic moduli of the in vivo artery. The resulting methods will be applicable to a wide range of patients, because they can be implemented on many clinical ultrasound instruments installed throughout the world. Method: We utilize acoustic radiation force (ARF) to produce propagating waves with wide bandwidth (frequency range) in the wall of the arteries and then measure the propagation motion with ultrafast ultrasound imaging. These measurements are made with high temporal resolution (< 20 milliseconds). From the wave motion, we calculate the viscoelastic moduli of the arterial wall throughout the cardiac cycle to evaluate viscoelastic properties of the artery at different blood pressures to quantify the nonlinear behavior of the arterial wall. Specifically, we use the wave velocity dispersion (variation of velocity with frequency) and attenuation properties of the wave modes generated using the ARF to estimate the viscoelastic properties of the arterial wall. To this end, we will continue to advance our modeling work with experts in numerical waveguide and finite element modeling and inversion to develop accurate and efficient algorithms that convert the measured dispersion and attenuation curves from ARF excitation to blood pressure-dependent viscoelastic moduli of the arterial wall to improve our understanding of wave propagation in the arterial wall. Models developed in this project will be used for fast inversions to solve for the material properties of the artery. The proposed ADUV method has high spatial (1-3 cm) resolution allowing local measurements to be made. Localized measurement of the viscoelastic and nonlinear material properties of the artery will provide new ultrasound-based biomarkers for assessment of cardiovascular health. We will validate these new biomarkers with clinical laboratory measurements in healthy subjects, patients with confirmed atherosclerotic cardiovascular disease, and patients who have risk factors for cardiovascular disease. Approach: To achieve these important goals, we will conduct a research program with the following Specific Aims: 1) Develop a suite of increasingly complex computational models of carotid arteries for computing dispersion and attenuation of guided waves generated using acoustic radiation force. 2) Develop inversion algorithms to robustly estimate arterial wall mechanical properties. 3) Validate the arterial dispersion ultrasound vibrometry measurements with clinical laboratory measurements in healthy human subjects, patients with confirmed atherosclerotic cardiovascular disease, and patients with cardiovascular risk factors.

摘要 背景：心血管疾病（CVD）是美国的主要死亡原因。据估计 8360万美国人目前至少有一种CVD，到2030年，40.5%的人口将 有某种形式的CVD，与2010年相比增加了约10%。动脉粥样硬化， CVD是一种以动脉的几种结构变化为特征的全身性病理状况。增加 动脉硬化主要是由于中膜胶原沉积增加和弹性蛋白断裂所致 动脉壁的一层，被认为是不良血管事件的独立风险因素。 动脉结构的改变导致动脉弹性和粘度的变化，这最近已经被证实。 早于闭塞性动脉粥样硬化疾病的临床表现。此外，这些变化往往 广泛分布，不限于单个动脉床，因此，有助于靶器官 损害动脉中的这些改变是已知和未知血管危险因素的顶点， 促进动脉粥样硬化病变的形成和进展， 动脉粥样硬化斑块破裂。我们的目标是开发一类新的动脉生物标志物， 血管壁的粘弹性和非线性材料特性。这些生物标志物可以在未来使用 通过提供广泛可用的 检测“症状前”血管疾病的技术，以改善CVD风险分层和随访 随后的干预。我们将使用声辐射力（ARF）产生传播波， 动脉壁中的频率带宽。将用数值色散方法分析波动， 我们称之为动脉弥散超声振动测量法（ADUV）。我们利用这些ADUV波的传播 定量和非侵入性地表征体内动脉的粘弹性模量的方法。的 由此产生的方法将适用于广泛的患者，因为它们可以在许多患者身上实施。 临床超声仪器安装在世界各地。方法：利用声辐射力 (ARF)以在动脉壁中产生具有宽带宽（频率范围）的传播波， 用超快超声成像测量传播运动。这些测量是用高 时间分辨率（< 20毫秒）。从波动，我们计算的粘弹性模量的 在整个心动周期中动脉壁的粘弹性，以评价动脉在不同血液条件下的粘弹性 压力来量化动脉壁的非线性行为。具体地说，我们用波的速度 色散（速度随频率的变化）和衰减特性的波模式产生的使用 ARF以估计动脉壁的粘弹性。为此，我们将继续推进我们的 与数值波导和有限元建模和反演方面的专家一起进行建模工作， 精确高效的算法，将测量的色散和衰减曲线从ARF转换为 激发动脉壁的血压依赖性粘弹性模量，以提高我们对 波在动脉壁中的传播。在这个项目中开发的模型将用于快速反演来解决 动脉的材料特性。所提出的ADUV方法具有高的空间分辨率（1-3 cm） 允许进行局部测量。粘弹性非线性材料的局部化测量 动脉的特性将为心血管健康的评估提供新的基于超声的生物标志物。 我们将在健康受试者、患有乳腺癌的患者和患有乳腺癌的患者中通过临床实验室测量验证这些新的生物标志物。 确诊的动脉粥样硬化性心血管疾病，以及有心血管疾病风险因素的患者 疾病方法：为了实现这些重要目标，我们将开展以下研究计划： 具体目标：1）开发一套日益复杂的颈动脉计算模型， 计算利用声辐射力产生的导波的色散和衰减。2)发展 反演算法来鲁棒地估计动脉壁机械特性。3)动脉离散度 超声振动测量与健康人受试者的临床实验室测量， 确诊为动脉粥样硬化性心血管疾病的患者和具有心血管危险因素的患者。