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栓塞。如果在斑块形成之前检测到动脉粥样硬化的发展，这些死亡是完全可以通过改变生活方式或药物治疗来预防的。同样，如果能够充分表征颈动脉斑块（即易损性斑块与稳定性斑块），则在疾病的晚期进行介入治疗和治疗具有良好的临床疗效。基于超声的靶向分子成像是一项新兴技术，具有提供颈动脉粥样硬化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中的应用仅限于一组狭窄的适应症（例如肝结节诊断），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止临床应用基于超声的靶向分子成像来预防中风的技术障碍。这一目标的成功实现将涉及一种新的靶向分子成像技术的体内演示，这种技术被称为基于单一光谱的靶向分子（SiSTM）成像，它具有超过95%的灵敏度和特异性，可以检测兔主动脉动脉粥样硬化的早期分子标志物。针对SiSTM成像的光束序列将进行优化，以增强灵敏度和特异性，包括自适应血流速度校正技术。此外，双频1.5D分子成像探针将被设计、制造并在研究扫描仪上实现。使用具有极端高胆固醇血症和晚期动脉粥样硬化遗传易感性的Watanabe遗传性高脂血症品系（WHHL）家兔，评估SiSTM成像在大动脉中的体内敏感性和特异性。疾病标志物的免疫组化结果将与SiSTM成像数据相关。

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.