Prevent Unnecessary Carotid Intervention and Stroke using Noninvasive Transcutaneous Ultrasound Thermal Strain Imaging (US-TSI)

项目总结 在这个应用中，我们试图开发一种经皮超声诱导热应变成像(US-TSI)。 供人类使用的探头和方案，并评估量化颈动脉粥样硬化中的脂质负荷的能力 颈动脉内膜切除术患者的斑块(AP)。美国数百万人罹患中风 年。尽管在治疗方面取得了进展，但在30年内死亡率仍高达~8%-12% 中风的日子。CEA或支架置入术等外科治疗有助于预防部分患者的中风 他们有明显的颈动脉狭窄。然而，只有一小部分颈动脉狭窄患者 出现短暂性脑缺血发作或中风的症状。目前的筛查工具在估计 狭窄程度，并提供一些一般的形态测量信息，但不能准确预测 损伤引起症状的风险更高。这导致了以下问题：哪些患者具有显著的颈动脉 疾病需要治疗，不确定性导致CEA或支架显著过度治疗， 通常会导致中风和心肌梗死等手术并发症。死后和体外 过去的研究和最近的临床试验都强烈地表明，脆弱的颈动脉AP具有脂质 Rich Core(LRC)。AP成分和形态的非侵入性特征以识别易破裂 损伤将是一种极其强大的临床工具。它提供了降低发病率、死亡率和 通过及早发现具有高风险特征的AP来实现医疗成本。仅在颈动脉，非侵入性AP 特征化有助于解决美国每年超过650,000例由颈动脉AP引起的缺血性中风 在减少用于中风后治疗和长期护理的300亿美元的同时，减少 不必要的颈动脉干预次数。经皮US-TSI是一种有前途的非侵入性治疗方法 评价颈动脉AP的血脂水平。我们先前的胆固醇喂养的兔子研究和先导的人类研究 证明US-TSI鉴定并定量了AP的百分比脂肪含量。当前的申请 优化US-TSI供人类使用是在这项工作的逻辑基础上进行的，这一工作支持了强有力的科学前提。这个 该项目的中心假设是US-TSI可以有效地定量人类颈动脉AP的脂质含量 研究对象。我们的长期目标是使用US-TSI创建颈动脉三重超声(CTS)，这将增强 目前的黄金标准，颈动脉双功超声(CDS)，通过允许检测AP的成分 以及狭窄的形态测量。如果成功，US-TSI将通过改善 颈动脉介入治疗的患者选择和颈动脉疾病患者的纵向随访。 此外，CTS还将提供一种评估新药治疗效果的手段。 在这项提议的范围内，中心假设将被检验如下：SA1：开发US-TSI探测器 和适合人类应用的协议。SA2：对US-TSI探针和方案进行临床评估 相关大动物急性胰腺炎模型。SA3：徒手US-TSI扫描在人体上的原位评价。

PROJECT SUMMARY In this application, we seek to develop a transcutaneous ultrasound-induced thermal strain imaging (US-TSI) probe and protocol for human use and evaluate the ability to quantify the lipid burden in carotid atherosclerotic plaques (AP) in patients undergoing carotid endarterectomy (CEA). Stroke affects millions in the U.S. each year. Although progress in the treatment has been made, the mortality rate remains high at ~8-12% within 30 days of a stroke. Surgical interventions such as CEA or stenting help to prevent stroke in a subset of patients who have significant carotid stenosis. However, only a small fraction of the patients with carotid stenosis develop symptoms of transient ischemic attack or stroke. Current screening tools are effective at estimating degree of stenosis and offer some general morphometric information but cannot accurately predict which lesions are at higher risk of causing symptoms. This leads to questions of which patients with significant carotid disease need to be treated and the uncertainty results in significant over-treatment of CEA or stenting, which often results in surgical complications like stroke and myocardial infarction. Post-mortem and ex vivo studies in the past as well as recent clinical trials strongly suggest that vulnerable carotid AP possess a lipid rich core (LRC). Noninvasive characterization of AP composition and morphology to identify rupture prone lesions would be an extremely powerful clinical tool. It offers the potential to reduce morbidity, mortality, and healthcare costs through early detection of AP with high-risk features. In the carotid alone, noninvasive AP characterization could help address 650,000+ ischemic strokes attributed to carotid AP in the U.S. annually while reducing the $30 billion for the treatment and long-term care following stroke as well as reducing the number of unnecessary carotid interventions. Transcutaneous US-TSI is a promising, noninvasive means of evaluating the lipids of carotid AP. Our previous cholesterol-fed rabbit study and pilot human subject study demonstrated that US-TSI identified and quantified percent lipid contents of AP. The current application for optimizing US-TSI for human use builds logically on this work, which supports a strong scientific premise. The central hypothesis in this project is that US-TSI can effectively quantify lipid contents of carotid AP in human subjects. Our long-term goal is to use US-TSI to create carotid triplex sonography (CTS) which will enhance the current gold standard, carotid duplex sonography (CDS), by allowing for detection of AP composition along with morphometric measures of stenosis. If successful, US-TSI will change clinical paradigm by improving patient selection for carotid interventions and the longitudinal follow up of patients with carotid disease. Furthermore, CTS will also provide a means of evaluating the treatment efficacy of newly developed drugs. Within the scope of this proposal the central hypothesis will be tested as follow: SA1: Develop a US-TSI probe and a protocol suitable for human application. SA2: Evaluate the US-TSI probe and the protocol in a clinically relevant large animal AP model. SA3: In situ evaluation of freehand US-TSI scan on human subjects.