基于流体力学与瘤壁影像融合的颅内动脉瘤破裂机制研究

Accurate assessment of rupture risk is the premise of patient-specific clinical treatment decision-making for intracranial aneurysms (IAs). Previously, we have proved that abnormal hemodynamic change plays an important role in initiation, development and rupture of IAs using Computational Fluid Dynamics (CFD) technique. However, due to the over simplification of boundary conditions, the hemodynamic pattern simulated by CFD may differ from that in vivo condition. Furthermore, the relationship of hemodynamics with pathological deterioration of aneurysm wall, which is another vital mechanism in aneurysm rupture process, is still unclear. The development of neuroimaging technique provides possible solutions for in vivo mechanical study on IA rupture. Therefore, in this project, we plan to simulate hemodynamic pattern of IA in vivo using 4D-MRI technique and then compare it with the result of CFD simulation to investigate the feasibility of in vivo hemodynamic analysis. Meanwhile, pathological remodeling and inflammation of aneurysmal wall will be detected using high resolution MR wall-imaging technique and then confirmed by histopathological analysis of resected aneurysm sample. Finally, the hemodynamic pattern and wall-imaging image will be combined and analyzed using image fusion method to detect the relationship between hemodynamics and deterioration of aneurysmal wall and its effect on IA rupture. This may help to explore a reliable and fast method to predict IA rupture in vivo and provide evidence for individual clinical decision-making for unruptured IAs.

颅内动脉瘤破裂风险评估是临床个体化治疗决策的前提。我们前期应用计算流体力学(CFD)技术证实异常血流动力学与破裂密切相关，但由于边界条件简化等问题，其与在体真实血流动力学状态可能存在差异。同时，血流动力学与影响动脉瘤破裂的又一重要因素—瘤壁退行性改变的偶联机制也缺乏在体验证。神经影像技术的发展为颅内动脉瘤破裂机制的在体研究提供了可能。因此，本课题将针对未破裂颅内动脉瘤破裂风险评估的核心问题，运用4D-MRI对动脉瘤血流动力学进行在体模拟，并与CFD模拟结果进行一致性分析；同时采用高分辨率磁共振管壁成像技术对动脉瘤瘤壁进行分析，并结合病理组织分析验证异常增强与退行性改变的相关性；后通过影像融合分析的方法，将血流动力学分布与瘤壁影像进行匹配分析，比较破裂动脉瘤与未破裂动脉瘤在体融合影像的差异，从而探索在体影像预测未破裂颅内动脉瘤破裂危险的可行性，为颅内动脉瘤的临床治疗决策提供依据。

颅内动脉瘤破裂风险评估是临床个体化治疗决策的前提，而血流动力学与瘤壁的相互作用是其破裂机制的核心。本课题主要从四个方面开展研究：1）基于高分辨率MRI管壁成像技术的颅内动脉瘤瘤壁强化危险因素分析：对颅内动脉瘤行管壁成像扫描，并对瘤壁强化程度进行分级，同时收集患者及动脉瘤相关特征。结果显示，动脉瘤大小与部位是瘤壁强化的独立危险因素。根据PHASES评分计算，随着动脉瘤破裂风险的增加，瘤壁强化程度显著提高；2）颅内动脉瘤血流动力学与瘤壁强化相关性分析：应用计算流体力学技术对动脉瘤进行血流动力学分析，同时基于三维影像计算形态学参数，探讨瘤壁强化与血流动力学及形态学之间的相互关系。结果显示，瘤壁强化程度与其血流动力学及形态学密切相关，高破裂风险动脉瘤形态学表现为体积大而不规则，血流动力学表现为低而多变的壁面切应力，而瘤壁表现为环形均匀的强化；3）人颅内动脉瘤瘤壁病理学特征与血流动力学的相关性分析：收集人体颅内动脉瘤标本与正常颞浅动脉组织标本，进行病理学染色分析与免疫组化检测，同时对颅内动脉瘤进行血流动力学分析，比较破裂与未破裂动脉瘤瘤壁特征与血流动力学特征的差异。结果显示，与颞浅动脉相比，动脉瘤壁内平滑肌细胞异常增殖、排列紊乱、细胞解离变性、间隙变大，同时SDF-1α、CXCR4及MMP-2等蛋白表达增多，而α-SMA表达减少。破裂动脉瘤伴有较低的WSS，与瘤壁炎症反应密切相关；4）4D-MRI技术对颅内动脉瘤血流动力学在体模拟探索：基于3D打印技术建立颅内动脉瘤模型，应用4D-MRI技术对动脉瘤模拟血流进行扫描，通过后处理建立颅内动脉瘤流场。结果显示，通过4D-MRI技术能够对血流动力学进行较为准确的扫描分析，并达到较高重建质量。本研究探讨了颅内动脉瘤血流动力学与瘤壁特征在动脉瘤破裂中的联合机制，明确高危动脉瘤的影像学及血流动力学特征，为临床个体化治疗决策提供指导。