Intravascular microstructural, chemical and biomechanical characterization of coronary plaques

冠状动脉斑块的血管内微观结构、化学和生物力学特征

• 批准号: 10669254
• 负责人: Nestor Uribe-Patarroyo
• 金额: $ 72.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669254
• 关键词: Address; Angiography; Arterial Fatty Streak; Atherosclerosis; Biomechanics; Cadaver; Cardiac; Catheterization; Catheters; Cause of Death; Cessation of life; Chemicals; Clinical; Clinical Research; Consumption; Coronary Arteriosclerosis; Coronary artery; Coronary heart disease; Development; Disease; Distal; Elements; Environment; Event; Family suidae; Funding; Future; Goals; Heart; Heart Diseases; Human; Image; Imaging Device; Imaging technology; Intervention; Lasers; Lateral; Lesion; Link; Measures; Mechanics; Methods; Modeling; Molecular; Myocardial Infarction; Near-Infrared Spectroscopy; Obstruction; Optical Coherence Tomography; Optics; Pathology; Pathway interactions; Patients; Procedures; Property; Research; Resolution; Risk; Robotics; Rupture; Source; Specificity; Speed; Stents; Structure; System; Techniques; Technology; Testing; Thinness; Time; Translations; Validation; biomechanical test; coronary plaque; elastography; human subject; imaging platform; improved outcome; individual patient; instrumentation; meter; novel; optical imaging; optimal treatments; percutaneous coronary intervention; preventive intervention; response; signal processing; technology development; technology validation; tool; treatment strategy; Address; Angiography; Arterial Fatty Streak; Atherosclerosis; Biomechanics; Cadaver; Cardiac; Catheterization; Catheters; Cause of Death; Cessation of life; Chemicals; Clinical; Clinical Research; Consumption; Coronary Arteriosclerosis; Coronary artery; Coronary heart disease; Development; Disease; Distal; Elements; Environment; Event; Family suidae; Funding; Future; Goals; Heart; Heart Diseases; Human; Image; Imaging Device; Imaging technology; Intervention; Lasers; Lateral; Lesion; Link; Measures; Mechanics; Methods; Modeling; Molecular; Myocardial Infarction; Near-Infrared Spectroscopy; Obstruction; Optical Coherence Tomography; Optics; Pathology; Pathway interactions; Patients; Procedures; Property; Research; Resolution; Risk; Robotics; Rupture; Source; Specificity; Speed; Stents; Structure; System; Techniques; Technology; Testing; Thinness; Time; Translations; Validation; biomechanical test; coronary plaque; elastography; human subject; imaging platform; improved outcome; individual patient; instrumentation; meter; novel; optical imaging; optimal treatments; percutaneous coronary intervention; preventive intervention; response; signal processing; technology development; technology validation; tool; treatment strategy

Heart disease is the leading cause of death in the US; the most prevalent type of heart disease is caused by atherosclerosis, the thickening of the vessel wall and creation of atherosclerotic plaque. Intravascular optical coherence tomography (IV-OCT) has enabled the imaging of coronary artery structures with un- precedented detail, and can be used to evaluate the response to percutaneous coronary intervention when treating atherosclerotic lesions. However, there remains a significant need to assess plaque vul- nerability: the determination of which mild lesions are likely to produce cardiac events in the future, and thus require immediate preventative interventional measures. Among lesion types, thin-cap fi- broatheromas (TCFA) are of particular concern since they are believed to be at increased risk of rup- ture; however, studies have found that only a fraction of TCFAs rupture. Although the likelihood of rupture has been linked to its mechanical stability, its chemical composition, and its microstructure, there is currently no technology capable of the biomechanical profiling of plaques in individual patients during intervention [without the need for time-consuming finite element modeling (FEM)] and the available methods for determining composition either lack specificity or spatial resolution. To address this significant need unmet by current intravascular imaging technology, we will develop an all-optical imaging platform that will profoundly broaden the access to accurate biomechanical, chemi- cal and microstructural profiling of coronary plaques in individual patients. Our novel platform will en- able a transformational leap in the current capability for comprehensive plaque characterization, in- cluding the assessment of plaque composition and vulnerability. We will leverage new ultra-fast laser sources to develop IV-OCT at 2,000 frames per second, enabling a host of powerful post-processing techniques that will enhance comprehensive characterization of plaques. In Aim 1 we will develop the enabling hardware to realize high-speed intravascular imaging. In Aim 2 we will develop hardware and signal processing to enable microstructural profiling at the 10×302 µm3 (depth×lateral) scale, chemical profiling at the 80×802 µm3 scale, and biomechanical profiling at the 60×602 µm3 scale in an all-optical technique without the need for FEM. In Aim 3 we will develop a novel validation platform based on a soft-robotics cardiac simulator of the biomechanical environment of the human beating heart. Our single imaging platform will facilitate clinical studies to determine the parameters of plaque vulner- ability, opening the door to the identification of optimal treatment strategies. Initially, it will become an invaluable research tool in atherosclerosis; later, it will have the potential to guide intervention in indi- vidual patients. After completion of the technological developments at the end of the proposed funding cycle, our platform will be ready for testing in human subjects.

心脏病是美国死亡的主要原因。最普遍的心脏病类型是引起的 通过动脉粥样硬化，血管壁的增厚和动脉粥样硬化斑块的产生。血管内 光学相干断层扫描（IV-OCT）使冠状动脉结构的成像具有未冠军 先例的细节，可用于评估对经皮冠状动脉干预的反应 治疗动脉粥样硬化病变时。但是，仍然需要评估斑块漏洞 神经性：确定哪些轻度病变可能会在将来产生心脏事件， 因此需要立即采取预防性介入措施。在病变类型中，薄帽fi- Broatheromas（TCFA）特别关注，因为据信它们的RUP风险增加 ture;但是，研究发现只有一小部分TCFA破裂。虽然很可能 破裂已与其机械稳定性，化学成分及其微观结构有关， 目前尚无单个患者斑块生物力学分析的技术 在干预期间[无需耗时的有限元建模（FEM）]和 确定组合物的可用方法要么缺乏特异性或空间分辨率。 为了通过当前的血管内成像技术无法满足这一重大需求，我们将开发一个 全光成像平台将深刻扩大获得准确的生物力学化学的访问权限 单个患者的冠状动脉斑块的CAL和微观结构分析。我们的小说平台将融合 能够在当前能力上具有变革性的飞跃，以实现全面的斑块表征， 包括评估牌匾组成和脆弱性。我们将利用新的超快速激光器 以每秒2,000帧开发IV-OCT的来源，从而实现了许多强大的后加工 将增强斑块全面表征的技术。在目标1中，我们将开发 使硬件能够实现高速血管内成像。在AIM 2中，我们将开发硬件， 信号处理以在10×302 µm3（深度×侧）尺度上启用微观结构分析，化学 以80×802 µm3量表进行分析，并以全光量为602 µm3的生物力学分析 无需FEM的技术。在AIM 3中，我们将基于A开发一个新颖的验证平台 人类跳动心脏的生物力学环境的软射击心脏模拟器。 我们的单个成像平台将促进临床研究，以确定斑块脆弱的参数 能力，打开识别最佳治疗策略的大门。最初，它将成为 动脉粥样硬化的宝贵研究工具；后来，它将有可能指导干预措施 视觉患者。在拟议的资金结束时完成技术发展后 循环，我们的平台将准备好在人类受试者中进行测试。