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: 10630204
• 负责人: KANG KIM
• 金额: $ 49.72万
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630204
• 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; 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; Non-Invasive Detection; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patient Selection; Patients; Persons; 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; Temperature; Testing; Time; Tissues; Transient Ischemic Attack; Translations; Treatment Efficacy; Ultrasonography; Uncertainty; Unnecessary Surgery; Water; Work; animal imaging; atherosclerosis risk; 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 detection; 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; ultrasound

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.

项目摘要 在此应用中，我们试图开发经皮超声诱导的热应变成像（US-TSI） 探针和人类使用方案，并评估量化颈动脉粥样硬化中脂质负担的能力 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 年。尽管已经取得了治疗的进展，但死亡率在30次内仍高约8-12％ 中风的日子。手术干预（例如CEA或支架）有助于防止患者中风 颈动脉狭窄很大的人。但是，只有一小部分颈动脉狭窄患者 出现短暂性缺血发作或中风的症状。当前的筛选工具可有效估算 狭窄程度并提供一些一般的形态计量学信息，但无法准确预测哪个 病变的风险更高，导致症状。这导致了哪些具有重要颈动脉的患者的问题 需要治疗疾病，不确定性会导致CEA或支架的大量过度治疗，这 通常会导致手术并发症如中风和心肌梗塞。验尸和前体内 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 Rich Core（LRC）。 AP组成和形态的无创表征，以识别易发的破裂 病变将是一种非常强大的临床工具。它提供了降低发病率，死亡率和 医疗保健费用通过早期发现具有高风险功能的AP来成本。仅在颈动脉中，无创ap 表征可以帮助解决美国每年归因于Carotid AP的650,000多个缺血性中风 同时减少了300亿美元的治疗和中风后的长期护理，并减少了 不必要的颈动脉干预措施的数量。经智商的美国-TSI是一种有前途的无创手段 评估颈动脉AP的脂质。我们以前的胆固醇喂养的兔子研究和试验人类学科研究 证明US-TSI确定了AP的脂质含量和量化百分比。当前的申请 在这项工作上以逻辑上的逻辑上建立了对人类使用的优化，这支持了强大的科学前提。这 该项目中的中心假设是，US-TSI可以有效地量化人类颈动脉AP的脂质含量 主题。我们的长期目标是使用US-TSI来创建颈动脉三重超声图（CTS），以增强 当前的黄金标准颈动脉双工超声图（CD），通过允许沿着AP组成检测 与狭窄的形态计量测量。如果成功，US-TSI将通过改进来改变临床范例 患者选择颈动脉干预措施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的治疗功效的方法。 在此提案范围内，中央假设将被测试如下：SA1：开发US-TSI探测 以及适合人类应用的协议。 SA2：在临床上评估US-TSI探针和方案 相关的大型动物AP模型。 SA3：对徒手US-TSI对人类受试者的现场评估。