Measurement of arterial mechanical properties during plaque progression

斑块进展过程中动脉机械特性的测量

• 批准号: 7671268
• 负责人: Seemantini K Nadkarni
• 金额: $ 21.75万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7671268
• 关键词: Acute; Animals; Apolipoprotein E; Area; Arterial Fatty Streak; Atherosclerosis; Biochemical Process; Biological Models; Biomechanics; Blood typing procedure; Cardiovascular Diseases; Cause of Death; Cholesterol; Clinical; Collagen; Coronary; Data; Development; Diagnostic; Diagnostic Procedure; Diet; Event; Fatty acid glycerol esters; Future; Goals; Histology; Human; Image; Imaging Techniques; Knock-out; Lasers; Measurement; Measures; Mechanics; Mediating; Methods; Metric; Modeling; Monitor; Motion; Mus; Necrosis; Optics; Pathogenesis; Patients; Pattern; Property; Research; Research Proposals; Risk; Rupture; Societies; Specimen; Staging; Structure; Techniques; Testing; Therapeutic; Thick; Thrombus; Time; Tissues; Work; diagnostic accuracy; experience; high risk; imaging modality; improved; in vivo; insight; instrument; light scattering; mouse model; novel; optical imaging; particle; response; tool; viscoelasticity

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.

描述（由申请人提供）：本研究的目标是开发和验证一种使用激光散斑成像来测量动脉粥样硬化斑块的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，是在动脉粥样硬化斑块的机械稳定性受损时引起的。评估动脉粥样硬化斑块机械特性的技术对于识别易于破裂的动脉粥样硬化斑块、指导治疗以及提供有关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）是一种测量组织中内源性颗粒布朗运动的新型光学技术，对于评估斑块粘弹性、成分和结构具有高度敏感性。我们之前对尸体动脉标本进行的工作表明，LSI 在诊断动脉粥样硬化斑块类型、测量胶原蛋白含量和坏死核心面积以及确定纤维帽厚度方面具有很高的准确性。当前提案的目标是开发一种测量内源颗粒的时间尺度和均方位移的方法，以计算准确评估血管粘弹性特性。该提案的目标源于我们之前研究 LSI 诊断潜力的经验。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力学特性。在斑块进展过程中，将随着时间的推移监测血管的粘弹性特性，并且在牺牲时，这些结果将与组织学发现相关。这项工作中开发的方法具有测量体内动脉粥样硬化斑块的生物力学特性以检测易破裂斑块的潜力，并可能促进改进治疗方法的开发。叙述：这项工作将为确定动脉粘弹性对斑块破裂发病机制的影响做出重大贡献。这项工作的完成将确定与斑块不稳定性相关的关键生物力学标志物，并将推动我们实现识别患者高风险斑块的最终目标。