Ultrasound-induced Thermal Strain Imaging for Arterial Plaque Characterization

描述（由申请人提供）：建议验证us诱导热应变成像（TSI）技术检测颈动脉斑块中的脂质含量。斑块以大脂质核心和薄纤维帽为特征，被认为是“易损斑块”或“易破裂斑块”。在这些潜在的致命斑块破裂之前识别它们是临床需要的，将有助于预测血管风险和指导治疗。目前用于识别斑块高风险特征的成像方法要么是侵入性的，要么是有限的。TSI可以为非侵入性和可靠地识别和表征动脉粥样硬化斑块（APs）提供替代的成像技术。脂类对声速具有负的温度依赖性，而水基组织则具有正的温度依赖性。TSI利用加热诱导组织温度升高，然后利用相位敏感、基于相关性的散斑跟踪算法从声速的局部变化中确定温度变化。TSI的特点是脂质和水基组织之间的强烈对比，这主要源于声速对比。在过去十年中，几个研究小组已经证明了基本概念和可行性，其中大部分是在体外进行的。为了保证TSI在临床上的实用性和可靠性，控制热源是非常重要的。我们建议使用连接到商业超声系统的单个线性探头，美国诱导TSI。本研究提出的总体目标是发展和评估us诱导的TSI以表征颈动脉斑块。基本假设是：1。美国线性探针可以设计并集成到商用美国成像系统中，为组织提供可控的美国能量输送，以诱导和成像热应变2。在AP内，局部TSI对比显示局部脂质核心的存在，TSI强度图测量脂质浓度和分布。3. 美国诱导的TSI可以提供一种强大、可靠和无创的工具来表征AP，特别是评估其脂质含量，这是赋予脆弱性的重要组成部分。这项技术应该很容易转化为诊断和管理颈动脉易损斑块的临床工具。必须研究范围广泛的技术和科学问题，以充分利用所提出的技术的能力和实用性。因此，此应用程序的三个具体目标是：1。开发一种优化的美国热源，与美国成像系统完全集成，在常规美国扫描期间为组织提供可控的能量输送。2. 开发一个强大的美国加热/成像脉冲序列和数据采集方案。3. 建立US诱导TSI与APs组织病理学的关系，特别是脂质核的评估。这种相关性将作为应用该技术作为局部斑块表征工具的可行性的指示。本研究将包括波束形成和组织热模型的计算机模拟，组织模拟模型的水箱实验，尸体解剖、截肢和颈动脉内膜切除术（CEA）的人体组织标本，以及高胆固醇喂养兔模型。

DESCRIPTION (provided by applicant): Validation of US-induced thermal strain imaging (TSI) technique to detect lipid contents in carotid artery plaques is proposed. Plaques characterized by a large lipid core and a thin fibrous cap have been identified as "vulnerable plaques", or "rupture-prone plaques. Identification of these potentially fatal plaques before their disruption is clinically desirable and will help predict vascular risk and guide therapies. Current imaging methods for identifying high risk features of plaque are either invasive or limited. TSI may provide alternative imaging technique to non-invasively and reliably identify and characterize atherosclerotic plaques (APs). Lipids have a negative temperature dependence of the sound speed, whereas water-based tissues have positive temperature dependence. TSI uses heating to induce a temperature rise in tissue and then determines the temperature change from local changes in sound speed using a phase-sensitive, correlation-based speckle tracking algorithm. TSI features strong contrast between lipids and water-based tissues, which stems primarily from sound speed contrast. The fundamental concept and feasibility has been demonstrated by several groups in the last decade mostly in vitro. For practicality and reliability of TSI in clinic, controlled heating source is important. We propose US-induced TSI using a single linear probe connected to a commercial ultrasound system. The overall goal proposed in this study is to develop and evaluate US-induced TSI to characterize carotid plaques. The fundamental hypotheses are: 1. An US linear probe can be designed and integrated into a commercial US imaging system to provide controlled US energy delivery to tissue to induce and image thermal strain 2. Within AP, the local TSI contrast indicates the presence of local lipid core and TSI intensity map measures lipid concentration and distribution. 3. US-induced TSI can provide a robust, reliable, and noninvasive tool for characterizing an AP, and in particular assessing its quantity of lipid, which is an important component that confers vulnerability. This technique should be easily translatable into a clinical tool for the diagnosis and management of carotid vulnerable plaques. A wide range of technical and scientific issues must be investigated to fully exploit the capabilities and practicality of the techniques proposed. Therefore, the three specific aims of this application are: 1. Develop an optimized US heating source fully integrated with an US imaging system to provide controlled energy delivery to tissue during routine US scanning. 2. Develop a robust US heating/imaging pulse sequence and data acquisition scheme. 3. Establish the relationship between US- induced TSI and the histopathology of APs, especially the assessment of the lipid core. This correlation will serve as an indication of the feasibility of applying this technique as a localized plaque characterization tool. The study will include computer simulations for beamforming and tissue thermal model, water tank experiments using the tissue mimicking phantoms, the human tissue specimens from autopsy, amputation and carotid endarterectomy (CEA), and high cholesterol-fed rabbit model. PUBLIC HEALTH RELEVANCE: Over 60 million Americans have some type of cardiovascular disease, and the estimated direct and indirect cost totals $368.4 billion in 2004, a significant burden on the economy. Atherosclerotic plaques, the most dangerous form of cardiovascular disease, can become unstable and rupture, releasing thrombogenic material such as lipid leading to blood clots totally blocking blood flow in the artery. These high-risk plaques, often called "vulnerable plaques," account for important clinical manifestations such as stroke and heart attack. Current imaging methods for identifying high risk features of plaque are either invasive or limited. Ultrasound- induced thermal strain imaging (TSI) may provide alternative imaging technique to non-invasively and reliably identify and characterize these vulnerable plaques. If successful, this method integrated into a commercial ultrasound scanner can be rapidly translated into clinical practice since it is based upon novel processing of ultrasound data that can be obtained conveniently and non-invasively from human subjects.