Ultrasound Targeted Molecular Imaging in Large Arteries to Diagnose Stroke Risk

描述(由申请人提供)：每年约有110万人死于颈动脉粥样硬化的栓子。如果在斑块形成之前发现动脉粥样硬化的发展，这些死亡是可以通过改变生活方式或药物治疗来高度预防的。同样，如果颈动脉斑块能够得到充分的表征(即脆弱斑块与稳定斑块)，介入治疗和治疗在疾病的后期阶段可以获得良好的临床疗效。基于超声的靶向分子成像是一种新兴的技术，具有提供颈动脉粥样硬化的早期检测和更具体的颈动脉斑块诊断和表征的潜力。然而，目前基于微泡的超声成像在临床上的应用仅限于一系列狭窄的适应症(例如，肝脏结节的诊断)，而目前靶向微泡成像的临床应用还不存在，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以超声为基础的靶向分子成像用于预防中风的临床应用的技术障碍。这一目标的成功实现将包括在体内展示一种新的靶向分子成像技术，称为基于奇异谱的靶向分子(SiSTM)成像，该技术具有超过95%的灵敏度和特异度，用于检测兔动脉粥样硬化的早期分子标志物。针对SiSTM成像的射束序列将进行优化，以提高灵敏度和特异度，包括自适应血流速度校正技术。此外，还将设计、制造并在研究扫描仪上实施双频1.5D分子成像探头。体内SiSTM成像的敏感性和特异性将使用表现出极高胆固醇血症和晚期动脉粥样硬化遗传易感性的Watanabe遗传性高脂血症(WHHL)兔来评估。疾病标志物的免疫组织化学结果将与SiSTM成像数据相关联。 公共卫生相关性：中风是世界上主要的死亡原因，每年估计有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、更低风险和更低成本的方法实现对颈动脉粥样硬化的早期或迅速治疗，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，并在活体兔研究中验证该技术用于检测心血管疾病的早期标志物。

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.