Intracoronary Laser Speckle Imaging for Atherosclerotic Plaque Diagnosis

描述（由申请方提供）：不稳定动脉粥样硬化斑块的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，血栓介导的缺血性心血管疾病仍然是死亡的主要原因。导致斑块易损性的过程是多因素的，并且广泛认为动脉粥样硬化的生物力学、组成和形态决定因素之间的复杂相互作用影响斑块稳定性。新型冠状动脉内成像技术的发展，提供有关这些因素的复合信息是至关重要的识别破裂倾向的动脉粥样硬化斑块，指导治疗，并提供有关斑块稳定的患者的见解。我们最近表明，激光散斑成像（LSI），一种新的光学技术，测量组织中内源性颗粒的布朗运动，是高度敏感的评价斑块粘弹性，组成和结构。我们之前的工作，尸体动脉标本进行的LSI诊断动脉粥样硬化斑块类型，测量胶原蛋白含量，坏死的核心面积，并确定纤维帽厚度具有很高的准确性。当前提案的目标是开发用于体内冠状动脉内使用的LSI系统和导管。我们设想，这项工作将可能产生一个单一的平台，以评估冠状动脉斑块的生物力学，组成和结构的患者。 本提案的目的是由我们先前在调查LSI的诊断潜力方面的经验和我们实验室在制造供人类使用的微型光学导管方面的专业知识所激发的。尽管我们已经证明了体外LSI的原理，但是能够在体内成像长冠状动脉段的冠状动脉内LSI导管和系统的开发提出了相当大的技术挑战。在本研究的目标1中，我们将专注于通过开发LSI仪器和能够在存在血流和心脏运动的情况下评价冠状动脉血管系统的冠状动脉内导管来克服这些挑战。LSI在识别斑块类型和表征结构特征方面的诊断准确性将使用离体动脉组织和体模研究来确定。在这项工作的目标2中，我们将使用人-猪冠状动脉异种移植活体动物模型证明冠状动脉内LSI的可行性，以允许在体内生理条件下评价人动脉粥样硬化斑块。随着本提案目标的成功实现，我们将开发出一种新型冠状动脉内LSI技术，并验证其临床适用性道路上的关键里程碑。叙述 急性冠状动脉综合征常由不稳定的冠状动脉斑块破裂引起。冠状动脉内激光散斑成像可能提供一种独特的方法来评估斑块稳定性的多个决定因素，并有助于检测患者的高风险冠状动脉斑块。

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.