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）：每年大约110万人死亡是颈动脉动脉粥样硬化的栓子的结果。如果在牙菌斑形成之前检测到动脉粥样硬化的发展，则可以通过生活方式的改变或药物治疗高度预防这些死亡。同样，如果可以充分地表征颈动脉斑块，则可以在疾病后期的后期获得介入治疗和治疗良好的临床功效（即脆弱的斑块与稳定的斑块）。基于超声的靶向分子成像代表了一项新兴技术，具有早期检测颈动脉粥样硬化和更具体的诊断和颈动脉斑块的特征的潜力。但是，诊所中基于微生物的超声成像的当前使用仅限于一组狭窄的适应症（例如肝结节诊断），并且目前对靶向微泡成像的临床使用很大程度上是由于与大动脉中与成像相关的技术挑战，这主要不存在。该项目的总体目标是打破目前防止基于超声的靶向分子成像的临床效果的技术障碍，以预防中风。该目标的成功实现将涉及一种新型靶向分子成像技术的体内证明，称为奇异谱的靶向分子（SISTM）成像，其灵敏度大于95％的敏感性和特异性，用于检测早期分子标记物用于兔主动脉动脉动脉粥样硬化的动脉粥样硬化。特定于SISTM成像的光束序列将被优化，以增强灵敏度和特异性，包括自适应血速校正技术。此外，将在研究扫描仪上设计，制造和实现双频率1.5D分子成像探针。大动脉中SISTM成像的体内敏感性和特异性将使用渡边可遗传的高脂血症菌株（WHHL）兔子进行评估，这些兔子表现出对极端高胆固醇血症和晚期动脉粥样硬化的遗传易感性。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，代表每年有720万人死亡。基于超声的分子成像策略是一种新兴技术，具有通过更简单，较低的风险和较低的成本方法实现早期或迅速治疗颈动脉粥样硬化的早期或迅速治疗，具有早期检测和预防中风的潜力。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，并验证在体内兔研究中检测早期标记的心血管疾病的技术。