基于串联狭窄法易损斑块小鼠模型的斑块破裂力学机理研究

Rupture of atherosclerotic plaques is the major cause of heart attack and stroke. Early detection and diagnosis of vulnerable plaques pre rupture is crucial for the risk stratification of patients with cardiovascular diseases. Different from the current available studies that are mainly focused on wall stress and wall shear stress, the proposed project aims to investigate the impact of the natural fatigue environment of cardiovascular system on plaque vulnerability and rupture. Tandem-stenosis induced ApoE-/- mouse vulnerable atherosclerosis model will be studies by combining medical imaging, biomechanical modelling, numerical simulation, mechanical test and pathological analysis to investigate the mechanism of plaque fatigue rupture. Plaque fatigue model will be developed to quantify the role of the plaque microstructure, the mechanical properties of plaque components and the fatigue environment on plaque vulnerability. A subject-specific and image-based biomechanical modeling technique will be developed in order to provide a framework for vulnerable plaque identification. Image-based three-dimensional computational models with multi-component plaque structure will be developed and solved numerically to simulate plaque rupture path and fatigue life. New risk indicators for vulnerable plaques will be identified for more accurate plaque assessment. Success of this project may lead to a better understanding of the underlying fatigue mechanism of plaque progression and rupture. It may provide us a useful clinical tool for the identification of high-risk patients with cardiovascular diseases, followed by large-scale patient follow-up studies.

动脉粥样硬化斑块破裂及继发血栓是导致急性冠状动脉综合症和脑卒中等心血管疾病发生的主要原因。因而，易损斑块的早期识别和诊断是防治心脑血管疾病的关键。与已有的基于血管壁应力、流体剪切应力等研究角度不同，本项目将针对“血管天然的疲劳环境对斑块的破裂有怎样的影响？”这一核心问题。以基因敲除小鼠串联狭窄法易损斑块模型为研究对象，采用医学成像、生物力学建模、数值模拟、力学实验和生物实验相结合的技术路线，从疲劳裂纹扩展及疲劳寿命的角度探索斑块的形态结构、组分特征、材料性能以及疲劳环境对斑块破裂的影响。进一步发展基于医学影像的个体化生物力学建模和计算方法，为易损斑块的量化判定和早期预警提供理论基础和技术手段。项目的成功开展将有助于我们深入了解斑块破坏的力学机理，找出斑块破裂风险的评价因子，为将来的临床实践提供新思路。

动脉粥样硬化斑块破裂及继发血栓是导致急性冠状动脉综合症和脑卒中等心血管疾病发生的主要原因。因而，易损斑块的早期识别和诊断是防治心脑血管疾病的关键。与已有的基于血管壁应力、流体剪切应力等研究角度不同，本项目主要针对“血管天然的疲劳环境对斑块的破裂有怎样的影响？”这一核心问题。以基因敲除小鼠串联狭窄法易损斑块模型为研究对象，采用了医学成像、生物力学建模、数值模拟、力学实验和生物实验相结合的技术路线，从疲劳裂纹扩展及疲劳寿命的角度探索了斑块的形态结构、组分特征、材料性能以及疲劳环境对斑块破裂的影响。发展了基于医学影像的个体化生物力学建模和计算方法；建立了斑块动态演变的数学力学模型，为易损斑块的量化判定和早期预警提供了理论基础和技术手段。本研究提高了我们对易损斑块在疲劳环境下破坏的机理的认识。通过结合动物实验和临床病人的跟踪随访研究，观察和分析斑块的中晚期生长过程中应力环境的变化和疲劳破裂机理。从而提高了我们对动脉粥样硬化机制的认识，促进了易损斑块的早期诊断和预警系统的建立，对降低心脑血管疾病死亡率和致残率具有深远意义。