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。动脉粥样硬化是心血管疾病的一个公认的原因，几十年来通常没有症状。因此，许多主要的心血管事件，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，包括心脏病风险评分，计算机断层扫描和超声，在准确性或应用方面受到限制。最近，磁共振成像（MRI）衍生的生物标志物，如壁切应力（WSS）和脉搏波速度（PWV）已显示出在早期检测动脉粥样硬化的潜力。WSS是对血管壁阻力的测量，其低值预测动脉粥样硬化斑块的发展。PWV是血液沿主动脉向下传播的量度，因此反映了动脉壁的硬度; PWV的高值指示动脉粥样硬化负荷。然而，过去使用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，要么在解剖覆盖范围上受到限制。此外，使用单独的MRI采集评价WSS和PWV。本研究的目的是开发和评价一种三维（3D）、三维流动敏感MRI技术，该技术在单次10分钟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，被称为PC VIPR，已经提供了上级的空间分辨率和解剖覆盖范围相比，在文献中的研究，但更大的时间分辨率是必要的，特别是对于PWV的准确分析。因此，我们将首先研究一种算法的使用，称为HYPR，它有可能加速PC VIPR的获取。我们将使用这种加速来提高时间分辨率，同时保持相同的十分钟扫描时间。一旦HYPR算法被整合到PC VIPR采集中，将通过流量体模研究确认从采集中获得的流量测量值。鉴于我们独特的3D MRI数据集，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采集将允许从单个十分钟扫描中同时评估WSS和PWV。最后，我们将研究这些测量WSS和PWV纵向在猪模型动脉粥样硬化继发于家族性高胆固醇血症（FH）。这些FH猪在一岁时发展动脉粥样硬化，而不进行干预或由于其基因突变而改变饮食。我们将比较我们的WSS和PWV测量FH和正常猪在2月龄，5月龄，8月龄和12月龄。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荷的能力，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.