Structural Stability of Carotid Plaque and Symptomatology

描述(申请人提供)：这项研究考察了动脉粥样硬化性颈动脉斑块结构稳定性与非运动性症状(包括脑萎缩和认知能力下降)发展之间关系中的“静默”卒中问题。它解决了颈动脉栓子在“无症状”中风及其认知后遗症中的作用问题。这项研究使用了人类颈动脉内膜切除术患者来研究三个特定的目标。第一种是利用超声将斑块弹性及其机械应变特征的发展与脉动联系起来，以及在这些机械应变特征点上溃疡、出血和稳定化纤维帽变薄的斑块的组织病理生理学。第二种检查是超声检测斑块中的弹性应变特征，以及经颅多普勒TCD可检测到的微栓子的存在。第三项研究着眼于超声应变缺陷、微栓子、认知能力下降以及局灶性和广泛性萎缩的脑MRI证据。了解结构斑块的异常，使颈动脉斑块机械不稳定并面临栓塞的风险，将显示出一种病理生理机制，这些人不仅可能遭受典型的发作性主要中风，而且可能因微栓子导致的脑部“无症状”中风和认知能力下降而导致功能进行性下降。 公共卫生相关性：脑血管疾病仍然是一个主要的健康问题，对老龄化人口的影响越来越大。研究表明，临床和“无症状”中风每年影响1100万美国人。动脉粥样硬化导致的血管老化是导致这一问题的主要原因。为此，我们建议对颈动脉粥样硬化进行研究，开发新的颈动脉斑块不稳定性标记物，这可能会导致多发性微栓子的存在，进而可能导致典型中风症状的增加以及认知能力的下降。如果成功，这项研究将极大地增加我们对动脉粥样硬化症状的病理生理学的理解，并导致潜在的新方法的发展，以无创地检测这种疾病。

DESCRIPTION (provided by applicant): This study examines the issue of "silent" strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including brain atrophy and cognitive decline. It addresses the question of the role of carotid emboli in "silent" stroke and their cognitive sequelae. The study uses human carotid endarterectomy patients to study three specific aims. The first uses ultrasound to relate plaque elasticity and its development of mechanical strain features with pulsation and the histopathophysiology of the plaque for ulcer, hemorrhage and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The second examines ultrasound detected elasticity strain features in the plaques and the presence of transcranial Doppler TCD detectable microemboli. The third looks at ultrasound strain deficits, microemboli, cognitive decline and brain MRI evidence of focal and generalized atrophy. Understanding the structural plaque abnormalities, which render a carotid plaque mechanically unstable and at risk of embolization will demonstrate a pathophysiologic mechanism in individuals who are likely to suffer not only classic episodic major strokes, but also functional progressive decline from the contribution of microemboli to cerebral "silent" stroke and cognitive decline. PUBLIC HEALTH RELEVANCE: Cerebrovascular disease remains a major health problem with increasing impact on an aging population. Studies suggest that clinical and "silent" stroke affects 11 million Americans per year. Vascular aging from atherosclerosis is a major contributor to this problem. For this reason, we propose a study of carotid atherosclerosis developing novel markers for carotid plaque instability which may result in the presence of multiple microemboli, which in turn may contribute to increased symptomatology, both classic strokes, as well as, cognitive decline. If successful, this study will greatly increase our understanding of the pathophysiology of symptoms from atherosclerosis, as well as, lead to the development of potential new measures to detect this disorder noninvasively.