基于计算流体力学和影像融合技术的踝间血压差纵向轨迹与缺血性脑卒中发病因果关系研究

To the best knowledge, our group reported for the first-time that non-invasive mechanical indicator of interankle systolic blood pressure difference was related with prevalent stroke independent of hypertension which is the strongest predictor of stroke based on a cross-sectional study, but their causal relationship inference across multiple time points and the underlying mechanism is still lack of systematic population follow-up study. It is the most direct and obvious effect of mechanical factors on the pathophysiology of cardiovascular system. However, the impact of biofluid mechanics on the vulnerability of atherosclerotic plaque is a problem that is often overlooked but of great importance in the field of ischemic stroke prediction. Here, in order to verify the causal relationship between the longitudinal trajectories of interankle systolic blood pressure difference with the incidence of ischemic stroke, the project will build on the long-term follow-up (8 years) cohort to establish an ischemic stroke risk prediction model and risk stratification tools based on interankle systolic blood pressure difference, and to use multi-modal and high-resolution magnetic resonance imaging to provide the different features of intracranial arterial remodeling, vascular lesion distribution, plaque vulnerability characteristics in the difference modes of longitudinal trajectories of interankle systolic blood pressure. Furthermore, we intent to uncover the biomechanical mechanism of the intracranial arterial blood flow field of ischemic stroke incident caused by the longitudinal trajectories of interankle systolic blood pressure from the point of mechanical load. Finally, we would reveal that longitudinal trajectories of interankle systolic blood pressure could be a warning sign of intracranial arterial plaque vulnerability. In short, our work will illustrate the power of interankle systolic blood pressure in the prediction of ischemic stroke, and the results will provide a new approach for the prevention and treatment of ischemic stroke from the perspective of medical and engineering joint.

本课题组首次基于横断面研究报道可诊室使用的无创力学指标踝间血压差是脑卒中患病的独立标志，但缺少多时间点的两者之间因果关系推断及潜在机制研究。由于力学因素对心血管系统病理生理过程的作用最直接和明显，且生物流体力学对颅内动脉粥样硬化性斑块易损性的影响是缺血性脑卒中预防领域常被忽视却很重要的问题，本项目将在长程（8年）随访队列的基础上，建立并验证基于踝间血压差纵向轨迹的缺血性脑卒中风险预测模型及危险分层工具；通过多模态及高分辨率核磁影像揭示踝间血压差多时间点特定变化谱的颅内动脉重塑、病变血管分布、斑块易损性等特点，进一步融合影像学和3D流-固耦合模型等计算流体力学技术，从机械负荷角度对踝间血压差纵向轨迹致缺血性脑卒中发病的颅内动脉血流场进行生物流体力学解释、阐明二者因果关系的机制，最终验证踝间血压差纵向轨迹亦是颅内动脉斑块稳定性下降的预警因子。通过有机的医工融合研究为缺血性脑卒中防治提供新途径。

脑卒中是中国成人死亡及长期致残的首要原因，发病率远高于欧美。缺血性脑卒中是其最常见类型，约占全部脑卒中的 60-80%。是我国目前面临的重大公共卫生问题和社会发展挑战。如何发展更准确的、具有种族等特异性的缺血性脑卒中风险评估工具，以便更好地对疾病进行预防和临床决策，成为近年来世界范围内的研究热点。. 本研究获取一个可供研究的踝间血压差与缺血性脑卒中发病因果关系的队列信息，并进行队列维护；建立踝间血压差与缺血性脑卒中发病的因果关系，当IAND≥15mmHg缺血性脑血管疾病的发病率显著增高，为该组人群的缺血性脑卒中发病的防治提供依据；发现踝间血压差差增加与左侧颈内动脉斑块独立相关；高血压伴踝间血压差增高者左侧大脑中动脉的收缩期血流速度、平均血流速度增高，左侧大脑中动脉的剪应力明显降低，踝间血压差≥7mmHg可能是左侧大脑中动脉粥样硬化的潜在危险标志。初步证实踝间血压差是颅内动脉斑块稳定性下降的预警因子。. 大脑中动脉是脑组织主要供应动脉之一，在颈内动脉的分支中最为粗大，是颈内动脉的直接延续，大脑半球约80%血液来自该动脉。大脑中动脉高度脆弱。颅内动脉狭窄较颅外狭窄更常见，其中大脑中动脉狭窄是最常见的。无论脑出血或脑梗死其最常累计的血管为大脑中动脉。在健康人群中，物理刺激等因素可明显导致优势大脑半球血流速度加快，如对指运动，握拳和肘部运动均能同样程度的激活运动对侧相应脑皮层，引起大脑中动脉血液流速的显著增高。右利手其左侧大脑皮层血液流速本身较高，存在血流动力学改变即血压增高，踝间差增大后，左侧大脑中动脉的流速可能更易受到累及。踝间差增高者左侧大脑中动脉的剪应力明显减低。剪应力影响内皮细胞炎症反应，高剪应力有利于维持内皮屏障(抗凝、抗炎、抗氧化)的生理特性；低剪应力引起内皮细胞死亡，降低了炎症细胞在内皮细胞表面滚动的速度，促进血小板和巨噬细胞粘附于动脉壁上，有利于动脉粥样硬化斑块的形成。. 踝间血压差测量简便，故对于基层缺血性脑卒中风险评估防治具有重要意义。