动脉粥样硬化斑块生长-应力关系的研究

Rupture of atherosclerotic plaques can often lead to stroke or heart attack. It is well accepted that plaque formation is associated with low or oscillatory wall shear stress. However, plaque growth often leads to lumen narrowing and thus results in an increase of wall shear stress. How plaque develops to be vulnerable and what leads to plaque rupture are still unknown. The objective of this proposed study is to investigate the association between plaque morphology and its mechanical enviroment during atherosclerosis progression. In vitro phantom, apoE-/- mice atherosclerosis model and patients with moderate carotid stenosis will be studied by combining computational modelling, magnetic resonance imaging (MRI), mechanical test and pathological analysis to investigate plaque progression, and quantify the critical blood flow and plaque stress/strain conditions under which plaque rupture is likely to occur. In vitro phantom study will be performed using an MRI-compatible physiological flow circulation system. A parametric finite element model and minimization algorithm will be developed to characterize the mechanical properties of plaque components. The results of the numerical simulations will be validated by both the phantom and in vivo MRI. Image segmentation and 3D plaque reconstruction will be performed based on multi-sequence MRI to characterize the difference of plaque morphology. MRI-based three-dimensional computational models with multi-component plaque structure and their interaction with blood flow will be developed and solved numerically to simulate plaque stability and identify suitable plaque rupture risk indicators for more accurate plaque assessment. The association between plaque morphology and stress will be investiagted during plaque progression. An MRI-based patient-specific modelling system and numerical method will be developed and this will provide a framework for vulnerable plaque identification. Success of this project will lead to quantitative understanding of the underlying biomechanics of plaque progression and rupture. It may provide us a useful clinical tool for the identification of vulnerable plaques in patients with moderate carotid stenosis.

动脉粥样硬化斑块的破裂是造成中风或心肌梗死的常见原因。斑块形成的生物力学机理和低剪切应力学说已被广泛认同，但随着斑块的生长，血管逐渐狭窄，斑块处于高剪切环境，斑块如何生长成为易损斑块和斑块最终如何破裂的生物力学机理尚不清楚。本项目将针对"斑块生长-应力关联规律"这一核心问题，分别以MRI-compatible 血管模型、基因敲除小鼠(ApoE-/-)套管法颈动脉粥样硬化模型和中度颈动脉狭窄的临床病人为研究对象，采用核磁成像、数值模拟、力学实验和生物实验相结合的技术路线，探索动脉粥样硬化斑块生长过程中斑块的形态结构、材料性能和应力环境的变化规律，以及各因素之间的关联；并进一步建立基于医学影像的个体化生物力学建模和计算方法系统，为易损斑块的量化判定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中晚期生长的生物力学机理，为将来的临床实践提供新思路。

动脉粥样硬化斑块的破裂是造成中风或心肌梗死的常见原因。斑块形成的生物力学机理和低剪切应力学说已被广泛认同，但随着斑块的生长，血管逐渐狭窄，斑块处于高剪切环境，斑块如何生长成为易损斑块和斑块最终如何破裂的生物力学机理尚不清楚。本项目针对“斑块生长-应力关联规律”这一核心问题，分别以MRI-compatible 血管模型、基因敲除小鼠(ApoE-/-)套管法颈动脉粥样硬化模型和中度颈动脉狭窄的临床病人为研究对象，采用了核磁成像、数值模拟、力学实验和生物实验相结合的技术路线，探索了动脉粥样硬化斑块生长过程中斑块的形态结构、炎症情况、材料性能和应力环境的变化规律。同时分析探究了影响斑块稳定性的各因素之间的关联，基本建立了个体化的基于核磁共振医学影像的生物力学建模和计算方法系统，为易损斑块的量化判定提供了力学评价方法和技术手段。项目的结果和研究数据提高了我们对斑块中晚期生长的生物力学机理的深入认识，为将来的临床实践提供了新思路。项目在四年里开展顺利，共发表论文31篇。培养了博士生2名，硕士生4名。