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

项目摘要 在这个应用中，我们寻求开发一种经皮超声诱导热应变成像（US-TSI） 并评估量化颈动脉粥样硬化中脂质负荷的能力 斑块（AP）进行颈动脉内膜切除术（CEA）的患者。中风影响美国数百万人， 年虽然治疗取得了进展，但30岁以内的死亡率仍高达8-12%。 中风的日子CEA或支架植入等外科干预有助于预防部分患者的卒中 颈动脉严重狭窄的病人然而，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。目前的筛选工具在估计 狭窄的程度，并提供一些一般的形态信息，但不能准确地预测， 病变引起症状的风险更高。这就引出了一个问题，即哪些患者的颈动脉 疾病需要治疗，不确定性导致CEA或支架的过度治疗， 经常导致外科并发症，如中风和心肌梗塞。死后和离体 过去的研究以及最近的临床试验强烈表明，脆弱的颈动脉AP具有脂质， 富芯（LRC）。AP成分和形态的非侵入性表征，以识别破裂倾向 病变将是一个非常强大的临床工具。它提供了降低发病率、死亡率和 通过早期检测具有高风险特征的AP来降低医疗成本。仅在颈动脉，非侵入性AP 表征可以帮助解决650，000+缺血性中风归因于颈动脉AP在美国每年 同时减少300亿美元用于中风后的治疗和长期护理， 一些不必要的颈动脉介入治疗。经皮US-TSI是一种很有前途的非侵入性方法， 评价颈动脉AP的血脂。我们之前的胆固醇喂养的兔子研究和试点人类受试者研究 表明US-TSI鉴定并定量了AP的脂质含量百分比。目前申请 优化US-TSI供人类使用的逻辑上建立在这项工作的基础上，这支持了一个强有力的科学前提。的 本项目的中心假设是US-TSI可以有效地定量人颈动脉AP的脂质含量 科目我们的长期目标是使用US-TSI创建颈动脉三重超声（CTS）， 目前的金标准，颈动脉双重超声检查（CDS），通过允许检测AP成分沿着 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开发药物疗效的方法。 在本提案的范围内，将对中心假设进行如下检验：SA 1：开发US-TSI探头 和适合人类应用的协议。SA 2：在临床上评价US-TSI探头和方案 相关大动物AP模型。SA 3：人体受试者徒手US-TSI扫描的原位评价。

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.