MR Biomarkers for the Noninvasive Evaluation & Early Detection of Atherosclerosis

用于无创评估的 MR 生物标志物

• 批准号: 8267252
• 负责人: Andrew L Wentland
• 金额: $ 3.04万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8267252
• 关键词: Acceleration; Address; Age-Months; Age-Years; Algorithms; Anatomy; Animal Model; Animals; Aorta; Arterial Fatty Streak; Atherosclerosis; Back; Biological Markers; Blood; Blood Vessels; Body Regions; Calcium; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Coronary; Data; Data Set; Dependence; Development; Diet Modification; Disease; Early Diagnosis; Evaluation; Event; Familial Hypercholesterolemia; Family suidae; Gene Mutation; Image; Imaging Techniques; Intervention; Ionizing radiation; Laboratories; Life Style; Literature; Magnetic Resonance Imaging; Measurement; Measures; Methods; Modeling; Modification; Myocardial Infarction; Patient Care; Patients; Phase; Physiologic pulse; Process; Radiation; Research Proposals; Resolution; Risk; Risk Assessment; Scanning; Secondary to; Staging; Stroke; Symptoms; Techniques; Technology; Thick; Time; Ultrasonography; United States; X-Ray Computed Tomography; arterial stiffness; compliance behavior; graphical user interface; imaging modality; improved; in vivo; intima media; kidney vascular structure; novel; reconstruction; shear stress; tool; treatment planning; user-friendly

DESCRIPTION (provided by applicant): Cardiovascular disease is a leading cause of death in the United States. Atherosclerosis is a well recognized cause of cardiovascular disease that develops over decades typically without symptoms. As a result, many major cardiovascular events, such as heart attacks and strokes, occur without forewarning. Methods of risk assessment and early detection of atherosclerosis are important tools for clinicians. However, current methods of assessment, including the Framingham Risk Score, computed tomography, and ultrasound have been limited either in accuracy or application. More recently, magnetic resonance imaging (MRI)-derived biomarkers, such as wall shear stress (WSS) and pulse wave velocity (PWV) have shown potential in the early detection of atherosclerosis. WSS is a measure of drag forces on vessel walls, low values of which are predictive for the development of atherosclerotic plaques. PWV is a measure of the propagation of blood down the aorta and thus reflects stiffness of the arterial wall; high values of PWV are indicative of atherosclerotic burden. However, past studies with these biomarkers have either been limited in spatial resolution for the measurement of WSS, in temporal resolution for the measurement of PWV, or in anatomic coverage. Additionally, WSS and PWV were evaluated with separate MRI acquisitions. The aim of this study is to develop and evaluate a three-dimensional (3D), three-directional flow-sensitive MRI technique that provides high spatial resolution, high temporal resolution, and large anatomic coverage in a single ten minute acquisition. Our proposed technique, termed PC VIPR, already provides superior spatial resolution and anatomic coverage compared to studies in the literature, but greater temporal resolution is needed, especially for an accurate analysis of PWV. Therefore, we will first investigate the use of an algorithm, termed HYPR that has the potential to accelerate the PC VIPR acquisition. We will use this acceleration to improve the temporal resolution while maintaining the same ten-minute scan time. Once the HYPR algorithm is incorporated into the PC VIPR acquisition, flow measurements derived from the acquisition will be validated with a flow phantom study. Given our unique 3D MRI data set, analysis tools and algorithms will be developed to compute the WSS and PWV measurements. The accelerated PC VIPR acquisition will thus allow for the simultaneous evaluation of WSS and PWV from a single ten-minute scan. Finally, we will investigate these measurements of WSS and PWV longitudinally in a swine model of atherosclerosis secondary to familial hypercholesterolemia (FH). These FH pigs develop atherosclerosis by one year of age without intervention or diet modifications as a result of their genetic mutation. We will compare our WSS and PWV measurements in both FH and normal swine at 2-, 5-, 8-, and 12-months of age. Such a study will allow us to investigate the ability of these MRI-derived biomarkers to predict and assess atherosclerotic burden, particularly in the early stages of disease.

描述（由申请人提供）：心血管疾病是美国的一个主要原因。动脉粥样硬化是公认的心血管疾病病因，其发展数十年通常没有任何症状。因此，许多重大心血管事件，例如心脏病发作和中风，都是在没有预警的情况下发生的。风险评估和动脉粥样硬化早期检测的方法是临床医生的重要工具。然而，目前的评估方法，包括弗雷明汉风险评分、计算机断层扫描和超声检查，在准确性或应用方面都受到限制。最近，磁共振成像（MRI）衍生的生物标志物，例如壁剪切应力（WSS）和脉搏波速度（PWV），在动脉粥样硬化的早期检测中显示出潜力。 WSS 是对血管壁阻力的测量，其低值预示着动脉粥样硬化斑块的形成。 PWV 是血液沿主动脉传播的量度，因此反映了动脉壁的硬度； PWV 高值表明动脉粥样硬化负担。然而，过去对这些生物标志物的研究要么局限于 WSS 测量的空间分辨率、PWV 测量的时间分辨率，要么仅限于解剖覆盖范围。此外，WSS 和 PWV 通过单独的 MRI 采集进行评估。本研究的目的是开发和评估三维 (3D)、三向流敏 MRI 技术，该技术可在十分钟的单次采集中提供高空间分辨率、高时间分辨率和大解剖覆盖范围。我们提出的技术称为 PC VIPR，与文献中的研究相比，已经提供了卓越的空间分辨率和解剖覆盖范围，但需要更高的时间分辨率，特别是对于 PWV 的准确分析。因此，我们将首先研究一种名为 HYPR 的算法的使用，该算法有可能加速 PC VIPR 的获取。我们将利用这种加速来提高时间分辨率，同时保持相同的十分钟扫描时间。一旦 HYPR 算法被纳入 PC VIPR 采集中，从采集中得出的流量测量结果将通过流量模型研究进行验证。鉴于我们独特的 3D MRI 数据集，我们将开发分析工具和算法来计算 WSS 和 PWV 测量值。因此，加速的 PC VIPR 采集将允许通过一次 10 分钟的扫描同时评估 WSS 和 PWV。最后，我们将在继发于家族性高胆固醇血症 (FH) 的猪动脉粥样硬化模型中纵向研究 WSS 和 PWV 的测量结果。这些 FH 猪由于基因突变，在没有干预或饮食调整的情况下，在一岁时就会出现动脉粥样硬化。我们将比较 2、5、8 和 12 月龄 FH 猪和正常猪的 WSS 和 PWV 测量值。这样的研究将使我们能够研究这些 MRI 衍生的生物标志物预测和评估动脉粥样硬化负担的能力，特别是在疾病的早期阶段。