ARFI ultrasound for noninvasive, Diagnostic atherosclerosis imaging

描述（由申请人提供）：在美国，虽然中风仍然是仅次于心脏病和癌症的主要死亡原因，也是造成严重长期残疾的主要原因（Rosamond等，2008年），但发病率的下降归因于包括血运重建术和他汀类药物治疗在内的干预措施（Collins等，2004年）。然而，现代诊断技术的不足限制了适当治疗的实施（Dhopra et al . 2007）。各种成像方法通常用于外周动脉粥样硬化的诊断，包括数字减影血管造影以及无创替代方法，如磁共振血管造影（MRA）和双工超声。虽然已知这些成像方法对于检测与血管管腔明显狭窄和/或血流阻塞相关的闭塞斑块是有效的，但它们对管腔特征的关注抑制了对动脉壁内非闭塞斑块的检测。此外，它们预测斑块引起脑血管事故（CVA）风险的能力尚未得到很好的证实（Raggi et al . 2005）。这些诊断缺陷导致高达50%的高危动脉粥样硬化斑块未被发现（Veller et al . 1993），这导致“突发性中风”，没有潜在疾病的预警或缓解能力。另一方面，在稳定斑块的情况下，过度积极的斑块风险评估会导致不必要的、高风险的侵入性手术，与强化药物治疗相比，没有额外的好处（Golledge et al . 2007）。对于一种有效的动脉粥样硬化成像方式，可以提高斑块检测和预测破裂风险，这显然是一个未被满足的需求。为了满足这一需求，我们的实验室正在开发一种新的、无创的动脉粥样硬化诊断成像技术——声辐射力脉冲（ARFI）超声——通过询问组织材料特性来利用组织成分。我们的初步研究表明，体内ARFI成像可检测闭塞性和非闭塞性斑块，并描述斑块胶原蛋白和弹性蛋白组成，这是预测斑块风险相关的物质特征（Behler et al . 2006）， （Behler et al . 2007a）， （Behler et al . 2007b）。该研究项目的长期目标是开发无创ARFI超声，用于早期斑块检测和识别引发CVA和心血管事件的高风险斑块。这条研究路线的吸引力不仅在于通过改进筛查和早期干预来减少心血管疾病对人类的巨大影响，而且还在于监测现有疗法和开发新疗法的潜力。作为实现我们长期目标的关键的第一步，拟议研究的目标是证明ARFI成像用于检测斑块并评估其外周动脉的组成和结构。我们假设在体内，经皮ARFI超声能够检测外周动脉的闭塞性和非闭塞性斑块，并评估斑块的组成。ARFI斑块检测和成分评估可以在FH猪髂动脉和人颈动脉中得到验证。公共卫生相关性：中风是美国第三大死亡原因，也是造成严重、长期残疾的主要原因。尽管及时和适当的治疗对于挽救生命至关重要，但传统诊断成像技术的缺陷阻碍了对疾病的提前预警并延误了治疗。本研究计划的目的是展示一种新的超声成像技术-声辐射力脉冲（ARFI）超声-用于改善动脉粥样硬化斑块和中风风险的诊断。

DESCRIPTION (provided by applicant): While stroke remains the primary cause of death behind heart disease and cancer and the leading cause of serious, long-term disability in the United States (Rosamond et al 2008), decreasing incidence has been attributed to interventions including revascularization and statin therapy (Collins et al 2004). However, administration of proper treatment is limited by inadequacies in modern diagnostic technologies (Dhopra et al 2007). A variety of imaging methods are routinely employed to diagnosis peripheral atherosclerosis, including digital subtraction angiography as well as noninvasive alternatives such as magnetic resonance angiography (MRA) and duplex ultrasound. Although these imaging methods are known to be effective for detecting occlusive plaques associated with pronounced narrowing of the vessel lumen and/or blood flow obstruction, their focus on lumenal features inhibits detection of nonocclusive plaques contained in arterial walls. Furthermore, their ability to predict plaque risk for causing cerebrovascular accident (CVA) has not been well established (Raggi et al 2005). These diagnostic shortcomings result in as many as 50% of high-risk atherosclerotic plaques going undetected (Veller et al 1993), which leads to `sudden stroke' with no advanced warning of underlying disease or the ability to mitigate. On the other hand, overly aggressive plaque risk assessment in the case of stable plaques leads to unnecessary, high-risk invasive procedures that confer no additional benefit over intensive drug therapy (Golledge et al 2007). There is a clear unmet need for a validated atherosclerosis imaging modality that can improve plaque detection and predict rupture risk. To address this need, our laboratory is developing a novel, noninvasive diagnostic atherosclerosis imaging technology - Acoustic Radiation Force Impulse (ARFI) ultrasound - which exploits tissue composition by interrogating tissue material properties. Our preliminary studies show that in vivo ARFI imaging detected occlusive and nonocclusive plaques and described plaque collagen and elastin composition, which are material features relevant to predicting plaque risk (Behler et al 2006), (Behler et al 2007a), (Behler et al 2007b). The long-term goal of this research program is to develop noninvasive ARFI ultrasound for early plaque detection and identification of plaques at high risk for initiating CVA as well as cardiovascular events. The attractiveness of this line of inquiry lies not only in the potential to diminish CVD's enormous human impact by improving screening and enabling early interventions, but also in the potential to monitor existing therapies and develop new ones. As a critical first step toward achieving our long-term goal, the objectives of the proposed research are to demonstrate ARFI imaging for detecting plaques and for assessing their composition and structure in peripheral arteries. We hypothesize that in vivo, transcutaneous ARFI ultrasound is capable of detecting occlusive and nonocclusive plaques in peripheral arteries and of assessing plaque composition. ARFI plaque detection and compositional assessment may be validated in FH pig iliac arteries and in human carotid arteries. PUBLIC HEALTH RELEVANCE: Stroke is the third leading cause of death and the primary cause of serious, long-term disability in the United States. Although timely and appropriate treatment is critical to saving lives, shortcomings in conventional diagnostic imaging technologies prevent advanced warning of the disease and delay therapy. The objectives of this research proposal are to demonstrate a novel ultrasound imaging technology - Acoustic Radiation Force Impulse (ARFI) ultrasound - for improved diagnosis of atherosclerotic plaques and stroke risk.