ARFI ultrasound for noninvasive, Diagnostic atherosclerosis imaging

描述(申请人提供)：虽然中风仍然是美国心脏病和癌症之后的主要死亡原因，也是导致严重、长期残疾的主要原因(Rosamond等人，2008年)，但发病率的下降要归功于包括血管重建和他汀类药物治疗在内的干预措施(Collins等人，2004年)。然而，现代诊断技术的不足限制了适当治疗的实施(DHopra等人，2007年)。各种成像方法被常规用于诊断周围动脉粥样硬化，包括数字减影血管造影术以及非侵入性替代方法，如磁共振血管造影术(MRA)和双功超声。虽然已知这些成像方法对于检测与显著狭窄的血管管腔和/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中包含的非闭塞斑块的检测。此外，他们预测导致脑血管意外(CVA)的斑块风险的能力还没有得到很好的确立(Raggi等人，2005年)。这些诊断缺陷导致多达50%的高危动脉粥样硬化斑块没有被发现(Veller等人，1993)，这导致了没有潜在疾病或缓解能力的提前警告的突然中风。另一方面，在稳定斑块的情况下，过度激进的斑块风险评估导致不必要的、高风险的侵入性程序，与强化药物治疗相比没有额外的好处(Golledge等人，2007年)。有一个明显的未得到满足的需求，验证动脉粥样硬化成像方式，可以改善斑块检测和预测破裂风险。为了满足这一需求，我们的实验室正在开发一种新型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-它通过询问组织材料属性来利用组织成分。我们的初步研究表明，体内ARFI成像检测到闭塞和非闭塞的斑块，并描述了斑块的胶原和弹性蛋白组成，这些是与预测斑块风险相关的材料特征(Behler等人2006)，(Behler等人2007a)，(Behler等人2007b)。这项研究计划的长期目标是开发非侵入性ARFI超声，用于早期检测斑块并识别引发CVA和心血管事件的高风险斑块。这一研究路线的吸引力不仅在于有可能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，还在于有可能监测现有的治疗方法并开发新的治疗方法。作为实现我们长期目标的关键的第一步，这项拟议研究的目标是展示用于检测斑块并评估其在外周动脉中的组成和结构的ARFI成像。我们假设，在活体内，经皮ARFI超声能够检测周围动脉闭塞和非闭塞的斑块，并评估斑块的成分。ARFI斑块检测和成分评估可以在FH猪的髂动脉和人的颈动脉中得到验证。

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.