大脑中动脉粥样硬化斑块的危险分层：高分辨率MRI和生物力学机制研究

Up to now, the effectiveness of treatment is not optimal for the patients of ischemic stroke with intracranial atherosclerosis. The diagnosis and treatment for it (such as middle cerebral artery, MCA) is a hotspot and difficulty of research in our country, because the understanding of relationship between the components of atherosclerotic plaque of MCA and the pathogenesis of cerebral ischemic events is limited. Our previous study found that non-invasive high-resolution magnetic resonance imaging (HR-MRI) and biomechanical analysis on plaque stability judgment has had great potential. This study intends to confirm the specificity and sensitivity of HR-MRI evaluation for intracranial plaque after comparing MRI of animal models and autopsy specimens with pathology, explore the relationship between plaque evolution and related clinical events with high resolution MRI quantitative analysis and dynamic observation of MCA plaque components in vivo, finally clarify the plaque stability and instability of the process using 3D fluid-structure interaction (FSI) technique to analyze the MCA luminal surface and plaque, combined with secondary ischemic events. The patients with intracranial atherosclerosis will be stratified by the real-time HR-MR monitoring of MCA plaque and treated with guiding of stratification. The optimal individualization of therapy for stratified patients will be carried out after following up and feedback from the effect of treatment.

以大脑中动脉（MCA）为代表的颅内动脉粥样硬化的诊治,是我国脑血管领域研究的热点及难点，由于对MCA粥样硬化斑块的发病机制、斑块成分特征与脑缺血事件关系的认识有限，因而目前治疗效果不佳。我们前期研究发现无创性高分辨率磁共振成像（HR-MRI）和生物力学分析对斑块稳定性的判断具有较大潜力。本研究拟用动物模型和尸检标本的MRI和病理对照研究，确认HR-MRI对颅内动脉斑块特征评价的特异性和敏感性；再通过活体高分辨率MRI定量分析和动态观测有症状患者的MCA斑块特征，探索斑块演进和相关临床事件的关系；最后采用3D流固耦合（FSI）技术分析MCA管腔表面和斑块力学状态，结合继发性缺血事件，阐明斑块稳定与失稳的过程。以实现用HR-MR管壁成像技术实时监测MCA斑块危险性，分层病人，指导治疗；并通过随访对治疗效果进行反馈，调整治疗方案，达到对病人的个体化最优化治疗。

在我国，脑卒中已超过冠心病成为头号杀手，33-55%的卒中病因是颅内动脉粥样硬化症，其中以大脑中动脉（MCA）粥样硬化最具危害性（发病率38%）。然而，目前对MCA粥样硬化斑块的发病机制、斑块成分特征与脑缺血事件关系的认识有限，依赖狭窄程度指导治疗的效果不甚理想（年复发风险>10%）。以颈动脉为代表的颅外动脉粥样硬化研究表明，无创性高分辨率磁共振（HR-MRI）成像和生物力学分析对斑块稳定性的判断发挥了积极作用。因此，本课题以HR-MRI管壁成像技术为主要手段围绕颅内动脉粥样硬化病变进行了一系列的研究。首先，通过对人类尸检标本的HR-MRI成像和病理检查，从离体方面检验MR管壁成像技术对颅内动脉粥样斑块的结构特征和组成成分显示的准确性和特异性；其次，通过临床患者的活体HR-MRI成像和随访，明确了责任斑块的HR-MRI形态学特征，在一定程度上阐明了HR-MRI管壁成像对以MCA为代表的颅内动脉粥样硬化疾病风险评估的价值；最后，基于MR几何图像和血压及流速数据，构建了症状性MCA斑块的生物力学模型，分析斑块结构中的载荷和血流作用在斑块表面的主要力学参数，为前瞻性评估颅内动脉粥样斑块的稳定性奠定了一定的基础。