Ultrasound-induced Thermal Strain Imaging for Arterial Plaque Characterization

描述（由申请人提供）： 验证超声诱导的热应变成像（TSI）技术检测颈动脉斑块中的脂质含量的建议。以大的脂质核心和薄的纤维帽为特征的斑块已被鉴定为“易损斑块”或“破裂倾向斑块”。在这些潜在的致命斑块破裂之前识别它们是临床上期望的，并且将有助于预测血管风险和指导治疗。目前用于识别斑块的高风险特征的成像方法是侵入性的或有限的。TSI可以提供替代成像技术，以非侵入性和可靠地识别和表征动脉粥样硬化斑块（AP）。脂质具有声速的负温度依赖性，而水基组织具有正温度依赖性。TSI使用加热来诱导组织中的温度升高，然后使用相敏的、基于相关性的斑点跟踪算法从声速的局部变化中确定温度变化。TSI具有脂质和水基组织之间的强烈对比，这主要源于声速对比。在过去的十年中，基本概念和可行性已被几个小组证明，主要是在体外。为了保证TSI在临床上的实用性和可靠性，可控热源是非常重要的。我们提出了US诱导TSI使用一个单一的线性探头连接到一个商业超声系统。本研究提出的总体目标是开发和评价超声诱导的TSI以表征颈动脉斑块。基本假设是：1。可以设计US线性探头并将其集成到商业US成像系统中，以向组织提供受控的US能量输送，从而诱导热应变2并对其成像。在AP内，局部TSI对比度指示局部脂质核心的存在，并且TSI强度图测量脂质浓度和分布。3. US诱导的TSI可以提供一个强大的，可靠的，非侵入性的工具来表征AP，特别是评估其脂质的量，这是一个重要的组成部分，赋予脆弱性。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。为了充分利用所提出的技术的能力和实用性，必须对广泛的技术和科学问题进行调查。因此，本申请的三个具体目的是：1.开发与超声成像系统完全集成的优化超声加热源，以便在常规超声扫描期间向组织提供受控的能量输送。2.开发稳健的US加热/成像脉冲序列和数据采集方案。3.建立超声诱导的TSI与AP组织病理学的关系，特别是脂质核心的评估。这种相关性将作为应用这种技术作为局部斑块表征工具的可行性的指示。该研究将包括波束形成和组织热模型的计算机模拟，使用组织模拟模型的水箱实验，来自尸检、截肢和颈动脉内膜切除术（CEA）的人体组织标本，以及高胆固醇喂养的兔子模型。 公共卫生相关性： 超过6000万美国人患有某种类型的心血管疾病，2004年估计直接和间接费用总计3684亿美元，这对经济构成了重大负担。动脉粥样硬化斑块是心血管疾病中最危险的形式，它会变得不稳定并破裂，释放出形成血栓的物质，如脂质，导致血栓完全阻塞动脉中的血流。这些高危斑块通常被称为“易损斑块”，是中风和心脏病发作等重要临床表现的原因。目前用于识别斑块的高风险特征的成像方法是侵入性的或有限的。超声诱导热应变成像（TSI）可以提供替代成像技术，以无创和可靠地识别和表征这些易损斑块。如果成功的话，这种集成到商业超声扫描仪中的方法可以迅速转化为临床实践，因为它是基于对超声数据的新处理，可以方便地和非侵入性地从人类受试者获得。

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.