Intracoronary Laser Speckle Imaging for Atherosclerotic Plaque Diagnosis

描述（由申请人提供）：不稳定动脉粥样硬化斑块破裂是导致血栓介导的缺血性心血管疾病的最常见事件，在工业化社会中，这仍然是导致死亡的主要原因。导致斑块易损的过程是多因素的，人们普遍认为动脉粥样硬化的生物力学、成分和形态决定因素之间存在复杂的相互作用，影响斑块的稳定性。新型冠状动脉内成像技术的发展提供了这些因素的综合信息，对于识别易破裂的动脉粥样硬化斑块、指导治疗以及为患者提供斑块稳定方面的见解至关重要。我们最近发现激光散斑成像（LSI）是一种新的光学技术，可以测量组织中内源性颗粒的布朗运动，对于评估斑块的粘弹性、组成和结构具有很高的灵敏度。我们之前在尸体动脉标本上进行的研究表明，LSI在诊断动脉粥样硬化斑块类型、测量胶原蛋白含量、坏死核心区域和确定纤维帽厚度方面具有很高的准确性。目前建议的目标是开发一种用于体内冠状动脉内使用的LSI系统和导管。我们设想这项工作将有可能产生一个单一的平台来评估患者冠状动脉斑块的生物力学、组成和结构。

DESCRIPTION (provided by applicant): The rupture of unstable atherosclerotic plaque is the most frequent event leading to thrombus mediated ischemic cardiovascular disease, which remains the leading cause of mortality in industrialized societies. The processes leading to plaque vulnerability are multi-factorial, and it is widely conceived that an intricate interplay between biomechanical, compositional and morphological determinants of atherosclerosis influences plaque stability. The development of novel intracoronary imaging techniques that provide composite information about these factors is vital for identifying rupture-prone atherosclerotic plaques, guiding therapy, and for providing insights regarding plaque stabilization in patients. We recently showed that Laser Speckle Imaging (LSI), a new optical technique which measures the Brownian motion of endogenous particles in tissue, is highly sensitive for evaluating plaque viscoelasticity, composition and structure. Our prior work, conducted on cadaveric arterial specimens demonstrated that LSI has high accuracy for diagnosing atherosclerotic plaque type, measuring collagen content, and necrotic core area, and determining fibrous cap thickness. The goal of the current proposal is to develop an LSI system and catheter for in vivo intracoronary use. We envision that this work will potentially yield a single platform to evaluate coronary plaque biomechanics, composition and structure in patients. The Aims of this proposal are motivated by our prior experience in investigating the diagnostic potential of LSI and the expertise of our laboratory in fabricating miniature optical catheters for human use. Although we have demonstrated the principles of LSI ex vivo, the development of an intracoronary LSI catheter and system capable of imaging long coronary segments in vivo presents considerable technical challenges. In Aim 1 of this research we will focus on overcoming these challenges by developing LSI instrumentation and an intracoronary catheter capable of evaluating coronary vasculature in the presence of blood flow and cardiac motion. The diagnostic accuracy of LSI in identifying plaque type and characterizing structural features will be determined using ex vivo arterial tissue and phantom studies. In Aim 2 of this work we will demonstrate the feasibility of intracoronary LSI using a human to swine coronary xenograft living animal model to permit evaluation of human atherosclerotic plaques under in vivo physiological conditions. With the successful culmination of the aims of this proposal, we will have developed a novel intracoronary LSI technique and validated critical milestones in its path to clinical applicability.Narrative Acute coronary syndromes frequently result from the rupture of unstable coronary plaque. Intracoronary Laser Speckle Imaging will potentially provide a unique method to evaluate multiple determinants of plaque stability and facilitate the detection of high-risk coronary plaques in patients.