Ultrasound-induced Thermal Strain Imaging for Arterial Plaque Characterization

描述（由申请人提供）：建议验证超声诱导热应变成像（TSI）技术以检测颈动脉斑块中的脂质含量。以大脂质核心和薄纤维帽为特征的斑块已被确定为“易损斑块”或“易破裂斑块”。在这些潜在致命的斑块破裂之前对其进行识别在临床上是可取的，并将有助于预测血管风险并指导治疗。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可以提供替代成像技术来非侵入性地、可靠地识别和表征动脉粥样硬化斑块(AP)。脂质具有负温度声速依赖性，而水基组织具有正温度依赖性，然后使用相敏、基于相关的散斑跟踪算法确定声速局部变化的温度变化，这主要源于声速对比。在过去的十年中，几个小组在体外证明了 TSI 的实用性和可靠性。本研究提出的总体目标是开发和评估超声诱导的 TSI 来表征颈动脉斑块。 基本假设是： 1. 可以设计超声线性探头并将其集成到商用超声成像系统中，以向组织提供受控的超声能量传输以诱导和成像热应变 2. 在 AP 内，局部 TSI 对比度表明局部脂质核心的存在，并且 TSI 强度图可测量脂质浓度和分布。一种强大、可靠和非侵入性的工具，用于表征 AP，特别是评估其脂质含量，这是导致易损性的重要组成部分。必须研究广泛的技术和科学问题，以充分利用所提出技术的功能和实用性。因此，该应用的三个具体目标是： 1. 开发与超声成像系统完全集成的优化超声加热源，以提供受控的能量传输。 2. 开发强大的 US 加热/成像脉冲序列和数据采集方案 3. 建立 US 诱导的 TSI 与 AP 的组织病理学之间的关系，特别是脂质核心的评估，这种相关性将表明应用该技术作为局部斑块表征工具的可行性。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、来自尸检的人体组织标本的水箱实验。和颈动脉内膜切除术（CEA），以及高胆固醇喂养的兔子模型。 公共健康相关性：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，对经济造成了沉重负担。动脉粥样硬化斑块是心血管疾病最危险的形式，它可能会变得不稳定和破裂，释放出脂质等血栓形成物质，导致血栓完全阻塞动脉中的血流。这些高风险斑块通常被称为“易损斑块”，是中风和心脏病等重要临床表现的原因。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。超声诱导热应变成像（TSI）可以提供替代成像技术，以非侵入性且可靠地识别和表征这些易损斑块。如果成功，这种集成到商用超声扫描仪中的方法可以快速转化为临床实践，因为它基于对超声数据的新颖处理，可以方便且非侵入性地从人类受试者获得超声数据。

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.