MR Biomarkers for the Noninvasive Evaluation & Early Detection of Atherosclerosis

描述(申请人提供)：心血管疾病是美国主要的死亡原因。动脉粥样硬化是公认的心血管疾病的原因，这种疾病在几十年内发展起来，通常没有症状。因此，许多重大心血管事件，如心脏病发作和中风，都是在没有预警的情况下发生的。风险评估方法和动脉粥样硬化的早期发现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，无论在准确性还是应用上都受到限制。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是一种测量血管壁上阻力的方法，它的低值预示着动脉粥样硬化斑块的发展。PWV是衡量血液沿主动脉传播的指标，因此反映了动脉壁的僵硬；PWV的高值表明动脉粥样硬化的负担。然而，过去对这些生物标志物的研究要么局限于测量WSS的空间分辨率，要么局限于测量PWV的时间分辨率，或者局限于解剖覆盖。此外，WSS和PWV通过单独的MRI采集进行评估。这项研究的目的是开发和评估一种三维(3D)、三向血流敏感的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率。我们提出的技术，称为PC VIPR，与文献中的研究相比，已经提供了更好的空间分辨率和解剖覆盖率，但需要更高的时间分辨率，特别是对于PWV的准确分析。因此，我们将首先调查一种称为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HYPR算法被合并到PC VIPR采集中，从采集中获得的流量测量将通过流体模研究进行验证。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。因此，加速的PC VIPR采集将允许从一次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)继发动脉粥样硬化的猪模型中纵向研究WSS和PWV的测量。由于基因突变，这些FH猪在一岁时出现动脉粥样硬化，没有进行干预或改变饮食。我们将比较我们在2个月、5个月、8个月和12个月龄的FH和正常猪的WSS和PWV测量。这样的研究将使我们能够调查这些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.