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

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.

心脏病是美国最主要的死亡原因； 动脉粥样硬化、血管壁增厚和血管内动脉粥样硬化斑块的形成。 光学相干断层扫描 (IV-OCT) 能够对冠状动脉结构进行非成像成像 先例细节，可用于评估经皮冠状动脉介入治疗的反应 然而，在治疗动脉粥样硬化病变时，仍然非常需要评估斑块损伤。 nerability：确定哪些轻微病变可能在未来产生心脏事件， 因此需要立即采取预防性干预措施。 呼吸瘤（TCFA）尤其值得关注，因为它们被认为具有更高的破裂风险。 然而，研究发现只有一小部分 TCFA 有破裂的可能性。 破裂与其机械稳定性、化学成分和微观结构有关， 目前尚无技术能够对个体患者的斑块进行生物力学分析 在干预期间[无需耗时的有限元建模（FEM）]和 用于确定成分的可用方法要么缺乏特异性，要么缺乏空间分辨率。 为了解决当前血管内成像技术无法满足的这一重大需求，我们将开发一种 全光学成像平台将深刻拓宽准确的生物力学、化学 我们的新平台将实现个体患者冠状动脉斑块的钙和微观结构分析。 能够在当前全面斑块表征的能力上实现转型飞跃， 包括评估牙菌斑成分和脆弱性，我们将利用新型超快激光。 以每秒 2,000 帧的速度开发 IV-OCT，从而实现一系列强大的后处理 在目标 1 中，我们将开发增强斑块综合表征的技术。 在目标 2 中，我们将开发硬件并实现高速血管内成像。 信号处理可实现 10×302 µm3（深度×横向）尺度的微观结构分析，化学 全光学系统中 80×802 µm3 尺度的分析和 60×602 µm3 尺度的生物力学分析 在目标 3 中，我们将开发一种基于 FEM 的新型验证平台。 人类跳动心脏的生物力学环境的软机器人心脏模拟器。 我们的单一成像平台将促进临床研究，以确定斑块脆弱性的参数 能力，为最佳识别治疗策略打开了大门。 动脉粥样硬化的宝贵研究工具；以后，它将有可能指导个体干预 个别患者在完成技术开发后建议资助。 周期后，我们的平台将准备好进行人体测试。