Mechanical characterization of carotid plaques for stroke risk assessment

中风是第五大死亡原因，也是可预防残疾的主要原因， 根据美国心脏协会的最新统计， 协会每年约有795，000人继续经历新的或经常性的 中风平均每40秒，美国就有人中风， 大约每四分钟就会死一个死亡率如此之高，部分原因是， 最先进的方法，如CT、MRI和超声，目前无法提供信息， 及时干预。识别高危、无症状颈动脉斑块患者， 因此，它们的低狭窄仍然是预防中风的一个难以捉摸但必不可少的步骤。当前 在临床实践中，颈动脉斑块破裂的风险评估是基于内膜的程度， 中膜厚度（IMT）和腔内狭窄，尽管它们不一定 与易损斑块或随后的破裂有关。因此，目前的临床模式不足 提供斑块稳定性信息。关于斑块稳定性的可靠信息将确保及时 治疗，尤其是无症状或低管腔狭窄患者， 仍然严重诊断不足。这些信息显示为关键信息，但临床上不可用 在于斑块顺应性和相关的血流。脂质斑块（通常 不太稳定且与缺血性中风有关）已经显示出具有明显的僵硬 从钙化的斑块。在中风患者中也报告了动脉僵硬度增加。的 因此，本研究的目的是通过优化颈动脉超声检查， 联合PWI和VFI方法（PWI+VFI）和量化依从性生物标志物 和流动，以便提供关于斑块稳定性的关键生物力学信息。报告的 研究中，我们的小组已经表明，在大型动物和中风患者中， 可以实现。我们已经证明PWI+VFI能够表征颈动脉 斑块基于其独特的硬度和流动性。在这项研究中，我们的目标是 颈动脉斑块的特征对缺血性卒中风险的最终可靠评估 基于斑块壁和血流生物标志物。因此，我们假设PWI可以显著地 增强常规血管超声的诊断能力。集合的队伍是 高度多学科，包括超声成像、生物力学、血管 放射学、病理学、神经学、血管外科学和生物统计学。根据提议， 研究，这种高度转化的技术可以很容易地集成在一个标准的声像图， 准确地告知颈动脉斑块的稳定性，从而及时进行后续治疗。

Stroke is the fifth leading cause of death and the primary cause of preventable disability and hospitalization in the U.S according to the most recent statistics by the American Heart Association. Each year, approximately 795,000 people continue to experience a new or recurrent stroke. On average, every 40 seconds, someone in the United States has a stroke, and someone dies of one approximately every 4 minutes. This high fatality rate is partly due to the fact that state-of-the-art methodologies such as CT, MRI and ultrasound are currently failing to inform timely intervention. Identification of patients with high-risk, asymptomatic carotid plaques despite their low stenoses remains thus an elusive but essential step in stroke prevention. In current clinical practice, the risk assessment of carotid plaque rupture is based on the degree of intima- media thickness (IMT) and endoluminal stenosis despite the fact that they do not necessarily correlate with vulnerable plaques or subsequent rupture. Current clinical modalities fall thus short in informing on plaque stability. Reliable information on plaque stability would ensure timely treatment, especially in asymptomatic or low endoluminal stenosis patients whose stroke risk remains severely underdiagnosed. Such information shown to be critical but clinically unavailable lies in the plaque compliance and the associated blood flow. Lipid plaques (which are typically less stable and are associated with ischemic stroke) have been shown to have distinct stiffness from calcified plaques. Increased arterial stiffness has also been reported in stroke patients. The objective of the proposed study is thus to amplify the role of carotid sonography by optimizing the combined PWI and VFI methodologies (PWI+VFI) and quantifying the biomarkers of compliance and flow in order to provide critical biomechanical information on plaque stability. In reported studies, our group has shown that plaque characterization in large animals and stroke patients can be achieved. We have demonstrated that PWI+VFI is capable of characterizing carotid plaques based on their distinct stiffness and flow. In this study, we aim towards the characterization of carotid plaques for the ultimately reliable assessment of ischemic stroke risk based on plaque wall and flow biomarkers. We thus hypothesize that PWI can significantly reinforce the diagnostic capability of a conventional vascular ultrasound. The team assembled is highly multi-disciplinary encompassing expertise in ultrasound imaging, biomechanics, vascular radiology, pathology, neurology, vascular surgery and biostatistics. Following the proposed studies, this highly translational technology could be readily integrated in a standard sonogram to accurately inform carotid plaque stability and thus subsequent timely treatment.