ARFI ultrasound for noninvasive, Diagnostic atherosclerosis imaging

描述（由申请人提供）：虽然卒中仍然是美国仅次于心脏病和癌症的主要死亡原因，也是严重长期残疾的主要原因（罗萨蒙德et al 2008），但发生率下降归因于包括血运重建和他汀类药物治疗在内的干预措施（柯林斯et al 2004）。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）。多种成像方法常规用于诊断外周动脉粥样硬化，包括数字减影血管造影以及非侵入性替代方法，如磁共振血管造影（MRA）和多普勒超声。尽管已知这些成像方法对于检测与血管腔的显著变窄和/或血流阻塞相关的闭塞性斑块是有效的，但是它们对管腔特征的关注抑制了对动脉壁中包含的非闭塞性斑块的检测。此外，其预测斑块导致脑血管意外（CVA）风险的能力尚未得到充分证实（Raggi et al 2005）。这些诊断缺陷导致多达50%的高风险动脉粥样硬化斑块未被检测到（Veller等，1993），这导致“突发性中风”，而没有潜在疾病的预先警告或减轻的能力。另一方面，在稳定斑块的情况下，过度积极的斑块风险评估导致不必要的高风险侵入性手术，与强化药物治疗相比没有额外的获益（Golledge et al 2007）。对于可以改善斑块检测和预测破裂风险的经验证的动脉粥样硬化成像模式，存在明显未满足的需求。为了满足这一需求，我们的实验室正在开发一种新的，非侵入性诊断动脉粥样硬化成像技术-声辐射力脉冲（ARFI）超声-它利用组织成分通过询问组织材料的属性。我们的初步研究表明，体内ARFI成像可检测到闭塞性和非闭塞性斑块，并描述了斑块胶原蛋白和弹性蛋白组成，这是与预测斑块风险相关的材料特征（Behler et al 2006）、（Behler et al 2007 a）、（Behler et al 2007 b）。这项研究计划的长期目标是开发非侵入性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。这一研究的吸引力不仅在于通过改善筛查和早期干预来减少CVD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第一步，拟议研究的目标是展示ARFI成像用于检测斑块并评估其在外周动脉中的组成和结构。我们假设在体内，经皮ARFI超声能够检测外周动脉中的闭塞性和非闭塞性斑块，并评估斑块成分。ARFI斑块检测和成分评估可以在FH猪髂动脉和人颈动脉中进行验证。公共卫生相关性：中风是美国第三大死亡原因，也是严重长期残疾的主要原因。虽然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点阻止了疾病的提前警告并延误了治疗。这项研究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.