Early Detection of Vascular Dysfunction Using Biomarkers from Lagrangian Carotid Strain Imaging

使用拉格朗日颈动脉应变成像生物标志物早期检测血管功能障碍

• 批准号: 10214678
• 负责人: TOMY VARGHESE
• 金额: $ 64.6万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10214678
• 关键词: 3-Dimensional; Age; Age-Years; Aging; Algorithms; Arterial Fatty Streak; Arteries; Atherosclerosis; Biochemical; Biological Markers; Blood; Blood Pressure; Blood Vessels; Blood flow; Cardiac; Carotid Arteries; Carotid Endarterectomy; Cerebrovascular system; Characteristics; Classification; Clinical; Code; Cognition; Color; Deposition; Development; Disease; Early Diagnosis; Embolism; Fostering; Frequencies; General Population; Goals; Grant; Guidelines; Histopathology; Human Volunteers; Hyperlipidemia; Hypertension; Image; Individual; Intervention; Lateral; Lead; Life Style Modification; Lipids; Location; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Medical; Methods; Modulus; Noise; Pathologic; Patients; Performance; Physiologic pulse; Physiological; Population; Populations at Risk; Protocols documentation; Research; Risk; Rupture; Scanning; Screening procedure; Sequoia; Severities; Signal Transduction; Stenosis; Stream; Stress; Stroke; Structure; Subgroup; System; Therapeutic Embolization; Time; Tissues; Ulcer; Ultrasonography; Validation; Variant; Vascular Cognitive Impairment; Vascular Diseases; Work; age group; age related; base; clinical imaging; clinically significant; cost; feeding; high risk population; human data; human subject; imaging approach; imaging study; improved; in vivo; indexing; innovation; interest; mechanical properties; novel; novel strategies; plaque lesion; pressure; reconstruction; response; screening; trend; vascular risk factor; volunteer

Abstract Current clinical criteria for treatment of atherosclerotic plaque, or atheromas, have focused primarily on percent stenosis of the vessel. However, measures of occlusion (percent stenosis) do not identify those plaques that are prone to rupture, which may release emboli into the blood stream feeding sensitive cerebral vasculature. A novel approach, Lagrangian carotid strain imaging, where tissue displacements are precisely measured during pulsation of blood through the artery has been developed. We propose to measure `strain indices,' that include the maximum accumulated axial, lateral, and shear strain estimated over the cardiac cycle, to probe the detailed mechanical properties of early plaque. We believe these strain indices will prove to be valuable vascular biomarkers to indicate vascular aging and possible plaque vulnerability. Our preliminary results demonstrate the ability to differentiate between soft and stiff regions in plaque under in-vivo clinical imaging conditions. Our definition of `vulnerable plaque' or `vulnerable patient' relies on the identification of lipidic depositions or softer plaques, i.e., those that undergo large axial or lateral deformations and/or large shearing strains during the cardiac cycle. Capability of strain tensor imaging and vascular biomarkers to characterize plaque severity from its early stages to a mature plaque lesion will be evaluated and quantified. A study on asymptomatic volunteers and patients also is proposed. The volunteer will provide values for vascular strain indices normalized to age-related vascular stiffening. The results will enable us to establish trends in age-related variations in vascular stiffness and to determine deviations that could establish vascular aging criteria. Interventions to reverse vascular aging might then be used, for example lifestyle modifications and common medical therapies. Strain imaging results will be validated and complimented by three- dimensional (3D) carotid magnetic resonance imaging (MRI) on a selected group of high-risk volunteers, along with 3D carotid MRI and 3D histopathological analysis of the entire excised plaque on patients to better understand plaque composition and structure. Validation of our results will foster use of real-time noninvasive ultrasound strain imaging as a screening tool for identifying human subjects susceptible to vascular aging and/or developing plaque prone to rupture or micro-embolization that could lead to `silent strokes' and possible vascular cognitive impairment. The patient study will also enable comparison of strain indices and carotid MRI to the ground truth, namely the excised plaque.

摘要 目前治疗动脉粥样硬化斑块或动脉粥样硬化的临床标准主要集中在 血管狭窄的百分比。然而，闭塞的测量（狭窄百分比）并不能识别出那些 容易破裂的斑块，这可能会释放栓子进入血流，为敏感的大脑供血。 脉管系统一种新的方法，拉格朗日颈动脉应变成像，其中组织位移精确 已经开发了在通过动脉的血液脉动期间测量的测量方法。我们建议测量`应变 指数，包括在心脏上估计的最大累积轴向、侧向和剪切应变 循环，以探测早期牙菌斑的详细机械性能。我们相信这些应变指数将被证明 是有价值的血管生物标志物，以指示血管老化和可能的斑块脆弱性。 我们的初步结果表明，有能力区分软，硬地区的斑块 在体内临床成像条件下。我们对“易损斑块”或“易损患者”的定义依赖于 识别沉积物或较软的斑块，即，那些经历大的轴向或横向 变形和/或大的剪切应变。应变张量成像能力， 从早期阶段到成熟斑块病变表征斑块严重性的血管生物标志物将是 评估和量化。 还提出了对无症状志愿者和患者的研究。志愿者将提供价值观 血管应变指数归一化为年龄相关的血管硬化。结果将使我们能够建立 血管硬度的年龄相关变化趋势，并确定可以建立血管硬度的偏差。 老化标准然后可能会使用逆转血管老化的干预措施，例如改变生活方式 和普通的医学治疗。应变成像结果将由三个方面进行验证和补充- 三维（3D）颈动脉磁共振成像（MRI）对选定的一组高危志愿者，沿着 用3D颈动脉MRI和3D组织病理学分析整个切除斑块对患者进行更好的 了解斑块的组成和结构。验证我们的结果将促进使用实时非侵入性 超声应变成像作为识别易受血管老化影响的人类受试者的筛选工具 和/或形成易于破裂或微栓塞的斑块，这可能导致“无症状中风”， 血管性认知障碍患者研究还将能够比较应变指数和颈动脉MRI 到地面的真相，即切除的斑块。