MR Biomarkers for the Noninvasive Evaluation & Early Detection of Atherosclerosis

描述（由申请人提供）：心血管疾病是美国的主要死亡原因。动脉粥样硬化是一种公认的心血管疾病的病因，其病程长达数十年，通常无症状。因此，许多重大心血管事件，如心脏病发作和中风，在没有预警的情况下发生。动脉粥样硬化的风险评估和早期检测方法是临床医生的重要工具。然而，目前的评估方法，包括Framingham风险评分、计算机断层扫描和超声波，在准确性和应用上都受到限制。最近，磁共振成像（MRI）衍生的生物标志物，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是衡量血管壁阻力的一种指标，其低值可预测动脉粥样硬化斑块的发展。PWV是血液沿主动脉传播的量度，因此反映动脉壁的硬度；高PWV值表明动脉粥样硬化负荷。然而，过去对这些生物标志物的研究要么在测量WSS的空间分辨率上受到限制，要么在测量PWV的时间分辨率上受到限制，要么在解剖覆盖上受到限制。此外，WSS和PWV分别通过MRI采集进行评估。本研究的目的是开发和评估一种三维（3D），三方向流动敏感的MRI技术，该技术在一次10分钟的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，与文献研究相比，已经提供了更好的空间分辨率和解剖覆盖范围，但需要更大的时间分辨率，特别是对于PWV的准确分析。因此，我们将首先研究一种称为HYPR的算法的使用，该算法有可能加速PC VIPR的获取。我们将使用这种加速来提高时间分辨率，同时保持相同的10分钟扫描时间。一旦将HYPR算法整合到PC VIPR采集中，从采集中获得的流量测量将通过流量模拟研究进行验证。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PC VIPR采集将允许在一次10分钟的扫描中同时评估WSS和PWV。最后，我们将在家族性高胆固醇血症（FH）继发动脉粥样硬化猪模型中纵向研究WSS和PWV的测量。由于基因突变，这些FH猪在没有干预或饮食改变的情况下在一岁时发生动脉粥样硬化。我们将比较2、5、8和12个月大的猪瘟猪和正常猪的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。

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.