Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque with High Stroke Risk

项目概要（摘要） 缺血性卒中是美国死亡和残疾的主要原因，其风险主要评估为- 按颈动脉狭窄程度分组。然而，狭窄程度作为卒中的生物标志物的不确定性 风险通常导致通过颈动脉内膜切除术（CEA）进行不必要的手术血运重建。据估计 在有CEA临床指征的患者中，14例狭窄50-69%的患者中只有1例发生神经- 逻辑症状，22例无症状患者中有1例狭窄70-99%，如果 未进行CEA。存在迫切但未满足的需要，以改善低水平患者的分化， 栓塞性中风的风险，从那些需要CEA，以防止它。这种需要可以满足的技术， 非侵入性地询问生物标志物，这些生物标志物已被确立为增加中风风险， 短暂性脑缺血发作（TIA），即：薄或破裂的纤维帽（TRFC），富脂坏死核心（LRNC）， 和斑块内出血（IPH）。这些颈动脉斑块的特征已经通过MRI和相关的血管造影来描述。 在多项临床研究中评估了当前和未来中风或短暂性脑缺血发作（TIA）的风险;如何- 然而，MRI对于筛查和常规监测来说过于昂贵。缺乏一种低成本、非侵入性的 一种可靠地描绘颈动脉斑块结构和组成的成像方法， 广泛的诊断应用代表了改善中风危险分层的主要差距。为了填补这一空白，我们 集团已经花了第一个五年的资助周期，这一赠款奖发展声辐射部队IM- 脉冲（ARFI）超声用于描绘人颈动脉粥样硬化斑块的结构和组成， 在体内，与空间匹配的组织学验证。我们的研究表明，ARFI描绘了 LRNC/IPH、胶原/钙沉积和体内人颈动脉斑块中的TRFC，测量TRFC厚度。 测量值低至0.49 mm -与颈动脉斑块破裂相关的平均厚度。的成功 迄今为止的研究促使ARFI技术进一步发展以增强颈动脉斑块成像。 具体而言，我们将利用ARFI加速度方差（VoA）成像22，23，更高的中心频率24， 谐波成像25，使TRFC、LRNC和IPH的单独识别和准确特征成为可能 尺寸测量我们将确定晚期ARFI的斑块特征与 同侧卒中或TIA近期病史。我们假设先进的经皮ARFI超声诊断- 在体内人颈动脉粥样硬化斑块中显示TRFC，LRNC和IPH，这些ARFI衍生的 斑块特征与最近的同侧中风或TIA有关。研究团队非常出色 准备继续这项工作; PI和所有Co-I先前合作成功完成了 该研究计划的前五年，以及对临床试验设计和执行的技术支持， 可通过北卡罗来纳州转化和临床科学（NCTraCS）研究所在萨德尔查珀尔获得 之丘

PROJECT SUMMARY (ABSTRACT) Risk for ischemic stroke, a leading cause of death and disability in the United States, is primarily assessed to- day by degree of carotid artery stenosis. However, insufficiencies in stenosis degree as a biomarker for stroke risk commonly lead to unnecessary surgical revascularization by carotid endarterectomy (CEA). It is estimated that, among patients with clinical indication for CEA, only 1 out of 14 with 50-69% stenosis experiencing neuro- logical symptoms, and 1 out of 22 asymptomatic patients with 70-99% stenosis, would have had a stroke if CEA was not performed. There exists an urgent yet unmet need to improve differentiation of patients at low risk of embolic stroke from those in need of CEA to prevent it. This need could be met by a technology capable of noninvasively interrogating biomarkers that have been established to confer increased risk of stroke and transient ischemic attack (TIA), namely: thin or ruptured fibrous cap (TRFC), lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH). These carotid plaque features have been delineated by MRI and associ- ated with current and future risk for stroke or transient ischemic attack (TIA) in several clinical studies; how- ever, MRI is prohibitively expensive for screening and routine monitoring. The lack of a low-cost, noninvasive imaging method that reliably delineates carotid plaque structure and composition and is suitable for wide- spread diagnostic application represents a major gap in improving stroke risk stratification. To fill this gap, our group has spent the first five-year funding cycle of this grant award developing Acoustic Radiation Force Im- pulse (ARFI) ultrasound for delineating the structure and composition of human carotid atherosclerotic plaque, in vivo, with spatially-matched histological validation. Our research has demonstrated that ARFI delineates LRNC/IPH, collagen/calcium deposits, and TRFC in human carotid plaque, in vivo, with TRFC thickness meas- urement as low as 0.49 mm - the mean thickness associated with carotid plaque rupture. The success of our investigations thus far motivates further advancement of ARFI technology to enhance carotid plaque imaging. Specifically, we will exploit ARFI Variance of Acceleration (VoA) imaging22,23, higher center frequencies24, and harmonic imaging25 to newly enable separate discrimination of TRFC, LRNC, and IPH and accurate feature size measurement. We will determine the association between advanced ARFI’s plaque characterization and recent history of ipsilateral stroke or TIA. We hypothesize that advanced transcutaneous ARFI ultrasound de- lineates TRFC, LRNC, and IPH in human carotid atherosclerotic plaques in vivo, and these ARFI-derived plaque features are associated with recent ipsilateral stroke or TIA. The research team is exceptionally well prepared to pursue this work; the PI and all Co-Is previously collaborated on the successful completion of the first five years of this research program, and skilled support for the design and execution of clinical trials is available through the North Carolina Translational and Clinical Sciences (NCTraCS) Institute at UNC Chapel Hill.