Measurement of arterial mechanical properties during plaque progression

描述（由申请人提供）：本研究的目的是开发和验证一种使用激光散斑成像测量动脉粥样硬化斑块内在生物力学特性的方法。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，当粥样硬化的机械稳定性受损时引起。评估动脉粥样硬化斑块的机械特性的技术对于识别易破裂的动脉粥样硬化斑块、指导治疗以及提供关于患者斑块稳定性的见解至关重要。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一种测量内源性颗粒的时间尺度和均方位移的方法，以准确计算和评价血管粘弹性。本建议的目的是由我们以前的经验，在调查LSI的诊断潜力的动机。随后，我们将使用这种方法来监测动脉粥样硬化小鼠模型中的血管机械特性。在斑块进展期间，将随时间监测血管的粘弹性，处死时，将这些结果与组织学结果相关联。在这项工作中开发的方法提出了在体内测量动脉粥样硬化斑块的生物力学特性，以检测破裂倾向的斑块的潜力，并可能促进改进的治疗方法的发展。叙述：这项工作将提出一个显着的贡献，在确定动脉粘弹性的斑块破裂的发病机制的影响。这项工作的完成将导致与斑块不稳定性相关的关键生物力学标志物的确定，并将使我们朝着识别患者中高风险斑块的最终目标迈进。

DESCRIPTION (provided by applicant): The goal of this research is to develop and validate a method using Laser Speckle Imaging to measure the intrinsic biomechanical properties of atherosclerotic plaques. The rupture of unstable atherosclerotic plaque, the most frequent event leading to thrombus mediated ischemic cardiovascular disease, is caused when the mechanical stability of the atheroma is compromised. Techniques that evaluate the mechanical properties of atherosclerotic plaques are 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 a method which measures the time scale and mean square displacement of endogenous particles to calculate accurately evaluate vessel viscoelastic properties. The Aims of this proposal are motivated by our prior experience in investigating the diagnostic potential of LSI. Subsequently, we will use this method to monitor vessel mechanical properties in a mouse model of atherosclerosis. Viscoelastic properties of the vessel will be monitored over time during plaque progression and at sacrifice these results will be correlated to histological findings. The methods developed in this work present the potential for measuring the biomechanical properties of atherosclerotic plaques in vivo to detect rupture prone plaques and may facilitate the development of improved therapeutic approaches. Narrative: This work will present a significant contribution in determining the influence of arterial viscoelasticity on the pathogenesis of plaque rupture. Completion of this work will result in the determination of a key biomechanical marker associated with plaque instability and will move us towards the eventual goal of identifying high-risk plaques in patients.