Intracoronary Laser Speckle Imaging for Atherosclerotic Plaque Diagnosis

描述(由申请人提供)：不稳定的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。导致斑块易损性的过程是多因素的，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复杂的相互作用影响斑块的稳定性。开发新的冠状动脉内成像技术，提供有关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，以及为患者提供关于斑块稳定性的见解至关重要。我们最近发现，激光散斑成像(LSI)是一种新的光学技术，它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、组成和结构具有高度的敏感性。我们先前在身体动脉标本上进行的工作表明，LSI在诊断动脉粥样硬化斑块类型、测量胶原含量和坏死核面积以及确定纤维帽厚度方面具有很高的准确性。目前这项提议的目标是开发一种供体内冠状动脉内使用的LSI系统和导管。我们预计，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，成分和结构的患者。 这项建议的目的是基于我们先前在调查大规模集成电路诊断潜力方面的经验，以及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。虽然我们已经在体外演示了LSI的原理，但开发一种能够在体内对冠状动脉长节段进行成像的冠状动脉内LSI导管和系统仍面临着相当大的技术挑战。在这项研究的目标1中，我们将致力于通过开发能够在存在血流和心脏运动的情况下评估冠状动脉血管系统的LSI仪器和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通过体外动脉组织和模体研究来确定。在这项工作的目标2中，我们将证明使用人到猪的异种冠状动脉移植活体动物模型进行冠状动脉内LSI的可行性，以允许在活体生理条件下评估人类动脉粥样硬化斑块。随着这项提议的目标的成功实现，我们将开发一种新的冠状动脉内LSI技术，并验证其临床应用道路上的关键里程碑。 急性冠脉综合征通常是由于不稳定的冠状动脉斑块破裂引起的。冠状动脉内激光散斑成像将可能提供一种独特的方法来评估斑块稳定性的多种决定因素，并有助于检测患者的高危冠状动脉斑块。

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.