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

使用无创经皮超声热应变成像 (US-TSI) 预防不必要的颈动脉干预和中风

• 批准号: 10192822
• 负责人: KANG KIM
• 金额: $ 67.48万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192822
• 关键词: Acoustics; Address; Affect; Algorithms; Animal Model; Animals; Area; Arterial Fatty Streak; Autopsy; Blood Vessels; Cardiac; Cardiovascular Diseases; Cardiovascular system; Caring; Carotid Arteries; Carotid Artery Plaques; Carotid Endarterectomy; Carotid Stenosis; Carotid stent; Cause of Death; Characteristics; Cholesterol; Clinic; Clinical; Clinical Research; Clinical Trials; Custom; Detection; Devices; Diagnosis; Disease; Early Diagnosis; Early identification; Ensure; Evaluation; Familial Hypercholesterolemia; Family suidae; Fatty acid glycerol esters; Foundations; Goals; Gold; Health Care Costs; Heating; Histologic; Histology; Human; Image; Image Analysis; In Situ; Intervention; Ischemic Stroke; Lesion; Lipids; Long-Term Care; Measures; Medical; Methods; Modeling; Morbidity - disease rate; Morphologic artifacts; Morphology; Motion; Motivation; Myocardial Infarction; Names; Noise; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patient Selection; Patients; Pharmaceutical Preparations; Pilot Projects; Protocols documentation; Reproducibility; Research; Risk; Rupture; Scanning; Schedule; Screening procedure; Severities; Signal Transduction; Speed; Stenosis; Stroke; Stroke prevention; Study Subject; Surgical complication; Symptoms; Techniques; Technology; Testing; Time; Tissues; Transient Ischemic Attack; Translations; Treatment Efficacy; Ultrasonography; Uncertainty; Unnecessary Surgery; Water; Work; animal imaging; atherosclerosis risk; base; clinical examination; clinical translation; clinically relevant; cost effective; effective therapy; experimental study; femoral artery; first-in-human; follow-up; high risk; human imaging; human subject; imaging probe; improved; in vivo; insight; life time cost; mortality; novel; overtreatment; patient subsets; prevent; programs; response; sound; stroke patient; stroke risk; stroke therapy; tool

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.

项目概要 在此应用中，我们寻求开发一种经皮超声诱导热应变成像 (US-TSI) 供人类使用的探针和方案，并评估量化颈动脉粥样硬化脂质负荷的能力 接受颈动脉内膜切除术（CEA）的患者的斑块（AP）。中风影响美国数百万人 年。尽管治疗已取得进展，但 30 年内死亡率仍然很高，约为 8-12% 中风的天数。 CEA 或支架置入术等手术干预措施有助于预防部分患者中风 有明显颈动脉狭窄的人。但只有一小部分患者患有颈动脉狭窄 出现短暂性脑缺血发作或中风的症状。当前的筛选工具可以有效地估计 狭窄程度并提供一些一般形态测量信息，但无法准确预测哪些 病变引起症状的风险较高。这就引出了一个问题：哪些患者有明显的颈动脉病变？ 疾病需要治疗，并且不确定性导致 CEA 或支架置入术的严重过度治疗，这 通常会导致中风和心肌梗塞等手术并发症。尸检和离体 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 丰富的核心（LRC）。对 AP 成分和形态进行无创表征，以识别破裂倾向 病变将是一种极其强大的临床工具。它具有降低发病率、死亡率和 通过及早发现具有高风险特征的 AP 来降低医疗费用。仅在颈动脉中，无创性 AP 在美国，特征描述可以帮助解决每年超过 650,000 例由颈动脉 AP 引起的缺血性中风 同时减少 300 亿美元用于中风后治疗和长期护理的费用，并减少 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方法 评估颈动脉AP的脂质。我们之前的胆固醇喂养兔子研究和试点人类受试者研究 证明 US-TSI 识别并量化了 AP 的脂质含量百分比。目前的申请为 优化 US-TSI 供人类使用在逻辑上建立在这项工作的基础上，该工作支持强有力的科学前提。这 该项目的中心假设是 US-TSI 可以有效量化人体颈动脉 AP 的脂质含量 科目。我们的长期目标是利用 US-TSI 创建颈动脉三重超声检查 (CTS)，这将增强 当前的黄金标准，颈动脉超声检查 (CDS)，可检测沿线的 AP 成分 狭窄的形态测量。如果成功，US-TSI 将通过改进来改变临床模式 颈动脉干预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治疗效果的手段。 在本提案的范围内，中心假设将进行如下测试： SA1：开发 US-TSI 探测器 以及适合人类应用的协议。 SA2：在临床中评估 US-TSI 探针和协议 相关大型动物AP模型。 SA3：对人体徒手 US-TSI 扫描进行原位评估。