Intravascular Photoacoustic Imaging of Atherosclerotic Plaques

描述（由申请人提供）：仅在美国，在血管造影评估中被认为“无关紧要”的斑块破裂将导致约50万人死亡。现有的筛查和诊断方法不足以在事件发生前识别受害者。因此，临床迫切需要一种能够识别和表征冠状动脉介入治疗过程中动脉粥样硬化斑块易感性的成像技术。我们研究计划的总体目标是开发一种体内成像技术-血管内光声成像-能够可视化动脉粥样硬化斑块的结构和功能特性。本项目的基本假设是血管内光声（IVPA）成像结合血管内超声（IVUS）成像是可能的，可以用来区分易损斑块，从而帮助干预前计划，干预本身，改善干预后的结果。最重要的是，提出的光声成像不会显著改变目前冠状动脉介入治疗的方案。为了充分探索血管内光声成像在介入心脏病学中的能力，必须解决广泛的技术、科学和临床问题。当前项目的中心主题是处理已知技术关注的领域，以便更广泛的开发工作可以以最小的风险进行。因此，R21应用程序的主要目的是开发并初步测试用于血管内应用的光声成像系统的原型。为了实现我们的目标，我们将首先设计和构建基于机械扫描的单元件换能器IVUS导管与可调谐激光源接口的血管内光声成像系统。我们还将发展光声和超声成像的理论和数值基础，以优化系统的性能。其次，我们将使用组织模拟幽灵来测试开发的成像系统。第三，开发的成像系统将使用动物组织样本进行测试，其中超声波和光声图像将与组织的组织学切片和生化分析相关联。最后，基于项目期间收集的见解，我们将概述血管内光声成像系统的设计和技术规范。动脉粥样硬化性心血管疾病每年导致1900多万人死亡，其中冠心病占大多数。尽管在冠心病患者的治疗方面取得了重大进展，但大量表面上健康的患者在没有任何先前症状的情况下突然死亡。现有的筛查和诊断方法不足以在事件发生前识别受害者——仅在美国，每年约有50万人死于血管造影评估认为“微不足道”的斑块破裂。因此，临床迫切需要一种能够识别和表征冠状动脉介入治疗（包括经皮球囊血管成形术、血管内支架置入术、消融/汽化和近距离治疗）中动脉粥样硬化斑块易损性的成像技术。

DESCRIPTION (provided by applicant): In the United States alone, approximately 500,000 deaths will result from rupture of plaques considered "insignificant" on an angiographic evaluation. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. Therefore, there is a definite and urgent clinical need for an imaging technique that can identify and characterize the vulnerability of atherosclerotic plaques during coronary artery interventions. The overall goal of our research program is to develop an in-vivo imaging technology - intravascular photoacoustic imaging - capable of visualizing both structural and functional properties of atherosclerotic plaques. The underlying hypothesis of this project is that intravascular photoacoustic (IVPA) imaging combined with intravascular ultrasound (IVUS) imaging is possible and can be used to distinguish vulnerable plaques, thus assisting pre-intervention planning, the intervention itself, and improving the post-intervention outcome. Most importantly, the proposed photoacoustic imaging will not significantly change the current protocol of coronary artery intervention. A wide range of technical, scientific and clinical problems must be addressed to fully explore the capabilities of intravascular photoacoustic imaging in interventional cardiology. The central theme of the current project is to address the areas of known technical concerns so that the broader developmental efforts may proceed with minimal risk. The main objective of this R21 application is, therefore, to develop and initially test a prototype of the photoacoustic imaging system for intravascular applications. To achieve our objective, we will first design and build the intravascular photoacoustic imaging system based on a mechanically scanned, single element transducer IVUS cathetrer interfaced with a tunable laser source. We will also develop both theoretical and numerical foundations for photoacoustic and ultrasound imaging to optimize the performance of the system. Second, we will test the developed imaging system using tissue mimicking phantoms. Third, the developed imaging system will be tested using animal tissue samples where ultrasonic and photoacoustic images will be correlated with histological slides and biochemical analysis of tissue. Finally, based on the insights gathered during the project, we will outline the design and technical specifications of an intravascular photoacoustic imaging system. Atherosclerotic cardiovascular disease results in more than 19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs - in the United States alone, approximately 500,000 deaths per year will result from rupture of plaques considered "insignificant" on an angiographic evaluation. Therefore, there is a definite and urgent clinical need for an imaging technique that can identify and characterize the vulnerability of atherosclerotic plaques during coronary artery interventions including percutaneous balloon angioplasty, endovascular stenting, ablation/vaporization and brachytherapy.