Ultrasound Targeted Molecular Imaging in Large Arteries to Diagnose Stroke Risk

大动脉超声靶向分子成像诊断中风风险

基本信息

批准号：
8371330
负责人：
John A Hossack
金额：
$ 34.47万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8371330
关键词：
Achievement Adhesions Aorta Arteries Atherosclerosis Behavior Binding Blood Blood flow Caliber Cardiovascular Diseases Carotid Arteries Carotid Artery Plaques Carotid Atherosclerotic Disease Cause of Death Cessation of life Clinic Clinical Computer software Contrast Sensitivity Data Development Diagnosis Disease Disease Marker Dose E-Selectin Early Diagnosis Embolism Emerging Technologies Event Exhibits Frequencies Gelatin Genetic Predisposition to Disease Goals Image Imaging Techniques Imaging technology Immunohistochemistry In Vitro Injury Integrins Laboratories Leukocytes Life Style Ligands Liver Measures Methods Microbubbles Molecular Molecular Target Monitor Motion Mus Nodule Oryctolagus cuniculus Pharmacotherapy Physiological Property Relative (related person)Research Risk Safety Selectins Sensitivity and Specificity Signal Transduction Source Specificity Speed Staging Stroke Stroke prevention Techniques Technology Testing Time Tissues Ultrasonography Validation Vascular Cell Adhesion Molecule-1 base clinical efficacy computerized data processing cost design diet and exercise disability economic cost flexibility hypercholesterolemia image processing imaging modality imaging probe in vivo innovation molecular imaging molecular marker new technology novel prevent programs receptor binding research study simulation smoking cessation therapy development

项目摘要

DESCRIPTION (provided by applicant): Approximately 1.1 million deaths each year are a result of emboli from carotid artery atherosclerosis. These deaths are highly preventable through lifestyle changes or drug therapy if the development of atherosclerosis is detected prior to plaque formation. Similarly, interventional treatment and therapy is available with good clinica efficacy at later stages of the disease if carotid plaques can be adequately characterized (i.e. vulnerable versus stable plaques). Ultrasound-based targeted molecular imaging represents an emerging technology with potential to provide both earlier detection of carotid atherosclerosis and more specific diagnosis and characterization of carotid plaques. However, current use of microbubble-based ultrasound imaging in the clinic is limited to a narrow set of indications (e.g. liver nodule diagnosis) and current clinical use of targeted microbubble imaging is non-existent largely due to technical challenges associated with imaging in large arteries. The overarching goal of this project is to break down the technological barriers currently preventing clinical utilty of ultrasound-based targeted molecular imaging for prevention of stroke. Successful achievement of this goal will involve in vivo demonstration of a novel targeted molecular imaging technology, called singular spectrum-based targeted molecular (SiSTM) imaging, with greater than 95% sensitivity and specificity for detection of early molecular markers for atherosclerosis in rabbit aorta arteries. Beam sequences specific to SiSTM imaging will be optimized for enhanced sensitivity and specificity including an adaptive blood velocity correction technique. Additionally, a dual frequency 1.5D molecular imaging probe will be designed, fabricated, and implemented on a research scanner. In vivo sensitivity and specificity of SiSTM imaging in large arteries will be assessed using Watanabe heritable hyperlipidemic strain (WHHL) rabbits exhibiting genetic predisposition for extreme hypercholesterolemia and advanced atherosclerosis. Immunohistochemistry results for disease markers will be correlated with SiSTM imaging data. PUBLIC HEALTH RELEVANCE: Stroke is a leading cause of death in the world representing an estimated 7.2 million deaths annually. Ultrasound-based molecular imaging strategies are an emerging technology with potential for early detection and prevention of stroke by enabling early or prompt therapy of carotid atherosclerosis using simpler, lower risk, and lower cost approaches. This project will develop a new ultrasound-based molecular imaging technology, called singular spectrum-based targeted molecular (SiSTM) imaging, and validate the technique for detection of early markers for cardiovascular disease in in vivo rabbit studies.

描述（由申请人提供）：每年约有 110 万人死于颈动脉粥样硬化栓塞。如果在斑块形成之前检测到动脉粥样硬化的发展，那么通过改变生活方式或药物治疗，这些死亡是可以高度预防的。同样，如果能够充分表征颈动脉斑块（即易损斑块与稳定斑块），介入治疗和治疗在疾病后期具有良好的临床疗效。基于超声的靶向分子成像代表了一种新兴技术，有可能提供颈动脉粥样硬化的早期检测以及颈动脉斑块的更具体的诊断和表征。然而，目前基于微泡的超声成像在临床上的使用仅限于一小部分适应症（例如肝结节诊断），并且目前临床上不存在靶向微泡成像，这主要是由于与大动脉成像相关的技术挑战。该项目的总体目标是打破目前阻碍基于超声的靶向分子成像预防中风的临床应用的技术障碍。成功实现这一目标将涉及一种新型靶向分子成像技术的体内演示，称为基于单谱的靶向分子 (SiSTM) 成像，该技术对于检测兔主动脉粥样硬化的早期分子标记物具有超过 95% 的灵敏度和特异性。 SiSTM 成像特有的光束序列将进行优化，以提高灵敏度和特异性，包括自适应血速校正技术。此外，还将在研究扫描仪上设计、制造和实施双频 1.5D 分子成像探头。将使用具有极端高胆固醇血症和晚期动脉粥样硬化遗传倾向的渡边遗传性高脂血症品系 (WHHL) 兔子来评估大动脉 SiSTM 成像的体内敏感性和特异性。疾病标志物的免疫组织化学结果将与 SiSTM 成像数据相关。公共卫生相关性：中风是世界上主要的死亡原因，估计每年有 720 万人死亡。基于超声的分子成像策略是一种新兴技术，通过使用更简单、风险更低和成本更低的方法实现颈动脉粥样硬化的早期或及时治疗，具有早期发现和预防中风的潜力。该项目将开发一种新的基于超声的分子成像技术，称为基于奇异谱的靶向分子（SiSTM）成像，并在兔子体内研究中验证该技术用于检测心血管疾病的早期标志物。