MCA斑块与脑血流变化对缺血性卒中转化的协同机制研究

The incidence of middle cerebral artery (MCA) territory ischemic stroke is very high, and the risk of stroke recurrence rate is up to 12.5%. The risk of stroke was closely related to MCA stenosis, vascular wall plaque and cerebral blood flow. We applied the high resolution (HR-MRI) vessel wall imaging and noninvasive cerebral perfusion assessment method (resting state functional MRI with time shift analysis-TSA, without contrast agent), and found MCA stenosis accompanied by plaque enhancement might be independent predictor of stroke, the level of cerebral perfusion in the rehabilitation of some stroke patients was independent of the degree of MCA stenosis, suggesting that plaque and perfusion could directly affect the outcome of MCA stenosis. Therefore, the synergistic action of plaque characteristics and cerebral perfusion in identifying high-risk patients, stroke risk stratification and prediction of stroke transformation is urgently needed to explore. This project will combine HR-MRI vessel wall imaging and resting state functional MRI with TSA technique to investigate the interactive effect of the two factors in stroke occurrence (incidence and severity) and different transformation (stable and evolutional). Results from this project will explore the imaging biomarkers for prediction of stroke transformation, and to develop a new accurate diagnosis of ischemic stroke, and to provide an important basis for early warning and individualized treatment of stroke.

大脑中动脉（MCA）供血区缺血性卒中发病率高，且卒中复发风险高达12.5%。卒中风险与MCA狭窄、血管壁斑块和脑血流密切相关。我们前期利用高分辨（HR-MRI）血管壁成像新技术和无创性脑灌注评估方法（无需对比剂的静息态功能磁共振时间移位分析,TSA），发现MCA狭窄伴有血管壁斑块强化可以独立预测卒中发生，且卒中康复患者的脑灌注水平独立于MCA狭窄程度，提示斑块和灌注可能直接影响MCA狭窄的结局。因此，斑块特性和脑灌注水平在识别高危患者、卒中风险分层和预测卒中转化中的协同机制急需探讨。本课题将联合HR-MRI管腔/管壁特征和TSA脑灌注水平，结合临床指标，通过横向和纵向随访研究，探讨MCA易损斑块与脑灌注两种因素在卒中发生（发生率及严重程度）和卒中转化（稳定、进展）中的协同作用，探寻预测卒中转化的影像生物标记物，研发缺血性脑卒中新的精准诊断方法，为卒中的早期预警和指导个体化治疗提供重要依据。

缺血性脑卒中是人类第二大死因和致残的主要原因，严重危害人类健康。大脑中动脉（middle cerebral artery, MCA）粥样硬化斑块及其引起的血管狭窄导致脑低灌注是引起缺血性脑卒中最常见的原因。易损斑块和脑低灌注同为MCA缺血性脑卒中发生和转化中的重要病理基础，但斑块特性和脑灌注之间相互关系及两者在脑卒中转化中的协同作用未知。本课题组成员提出的利用静息态BOLD数据无创评估脑灌注水平，将有助于本项目的顺利开展。本项目中，我们对40例亚急性期脑卒中患者行磁共振检查，利用静息态功能磁共振数据采用时间移位分析（TSA）方法，检测脑低灌注缺血区，并于常规脑灌注检测方法对比，发现14例伴有颅内大动脉严重狭窄或闭塞患者，两者检测脑缺血能力与范围相当，其中1例具有侧枝循环的灌注没有异常。剩余16例血管没有明显狭窄的灌注均无明显异常。本研究提示基于不打药的静息态数据的TSA 分析方法是常规打药功能磁共振检测脑灌注的一种可靠替代方法。此外，我们对41例一侧颅内动脉粥样硬化患者行磁共振检测，测定病灶侧与对侧白质高信号体积，并分别分割为皮层下白质高信号及脑室周围白质高信号。发现粥样硬化侧与对侧白质体积差异存统计学意义，病灶侧皮层下及总和白质高信号体积较对侧增高；多元回归分析发现，斑块强化及TTP-ASPECTS评估的低灌注与白质高信号体积增高有关，而仅有低灌注、高龄、高血压与ICAS侧脑白质高信号体积有关。该研究结果提示动脉粥样硬化斑块与大脑半球间脑白质高信号不对称性有关，提示针对性的斑块治疗有助于稳定脑白质高信号的进展。总体来说，本项目发现了易损斑块、低灌注在缺血性卒中及脑白质高信号患者的作用机制，为探寻缺血性脑血管病的影像学机制及指导临床治疗奠定了基础。