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基于个性化Willis环体外模型的脑动脉瘤血流动力学研究
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摘要
我国蛛网膜下腔出血的年发病率为5/100,000-20/100,000人,其中动脉瘤所致者占52%。颈内动脉眼动脉段动脉瘤发生在颈内动脉和眼动脉的分叉处,占颅内动脉瘤的0.47%-9.26%。由于其手术空间狭小,一直是神经外科手术的技术难点。另一方面,由于有许多因素都会影响动脉瘤的形成和增长,有必要采用能够反映局部和整体脑血流特性的方法,以揭示动脉瘤形成因素之间的相互作用。
     为了探究动脉瘤的形成机理,本文通过生物力学方法研制出基于脑部计算机断层扫描图像的个性化脑Willis环体外模型,保证了模型结构的真实性,实验模型的透光性和可重复性。并通过体外灌流实验观测颈内动脉眼动脉段动脉瘤以及整个Willis环内的流动和溶液传输特性,考察了Willis环通过交通动脉的血液调节作用,揭示了动脉瘤的存在对脑部供血的影响。
     本文的研究内容包括以下三个方面:
     ●复杂血管的计算机三维重建。首先基于Simpleware软件构建了Willis环的三维有限元模型。然后开发了图像处理和结构化六面体网格生成算法,解决了复杂血管分叉连接问题,并成功应用于不同分叉血管及肾脏的三维重建,经过适当扩展,可以应用到Willis环的三维模型重建。为真实结构血管内血流动力学分析提供了较好的计算建模方法。
     ●个性化Willis环透明体外模型的研制。开发了一套基于医学图像制作复杂结构体外模型的方法。这一方法通过单纯的模板堆砌,及不同热物性及光学材料的组合,实现了复杂血管网模型的一次成型。为复杂血管体外模型的制作,提供了除三维打印机以外的低成本、快捷有效的方法。
     ●Willis环内流动特性的可视化实验。首先搭建了体外灌流实验平台。通过植入U型管超声体模实验确立了压力,流量以及温度等参数的测试方法。并通过在左右两侧颈动脉以及基底动脉注入墨水溶液,考察了不同结构Willis环内的溶液传输特性。最后,运用特殊的示踪粒子灌注液,并结合高速摄影仪考察了Willis环内的流动特性。首次获得了脑动脉瘤与Willis环内流动特性相互作用的实验结果。
     Willis环墨水溶液传输特性实验表明,不同动脉所供给的组织区域不同,其中,颈动脉基本仅供应同侧的中脑动脉、前脑动脉、眼动脉区域,而来自基底动脉的溶液所供给的区域较广,甚至可以覆盖整个Willis环。当Willis环结构改变后,颈动脉和基底动脉所供给的区域将会发生变化。
     流动可视化实验进一步表明,发生颈动脉-眼动脉瘤后,除了两侧眼动脉流
     量外,左右两侧Willis环内的流量较没有动脉瘤时更加平衡,三个交通动脉的流量明显升高,说明Willis环通过交通动脉的调节作用增加显著。另外,当发生动脉瘤以后,同侧的眼动脉的流量增大,左右两侧眼动脉流量差距明显升高。最后,从瞬时速度分布中可以看出,在无瘤和有瘤的完整Willis环结构内,后交通动脉的瞬态速度波动最为明显,有时会出现回流。
     这些结果表明,颈动脉-眼动脉瘤的存在明显地改变了整个Willis环内以及眼动脉的流动和传质特性,在Willis环内通过交通动脉使得脑组织内的血流达到重新分配。这一研究从整体和局部揭示了动脉瘤对脑血流的影响,将为探究动脉瘤的发生机制提供有益的帮助。
The annual incident of subarachnoid hemorrhage (SAH) is5-20in100,000people in China, among which52%are caused by aneurysm. Internal carotid artery-ophthalmic artery aneurysm appears at the bifurcation of internal carotid artery and ophthalmic artery, accounting for0.47%-9.26%of the intracranial aneurysms and its treatment has been a neurosurgical challenging problem due to its narrow operative space. On the other hand, as many concurrent factors appear to underline the occurrence and development of cerebral aneurysm, an integrated approach for revealing global and local features of blood flow in the cerebral circulation is required to understand the interaction between the different factors.
     Aiming at studying the mechanism of aneurysm occurrence and its effect on the blood flow supplying to the brain tissue, the in-vitro patient-specific models of the circle of Willis with and without an aneurysm were developed based on computerized tomography images by biomechanical approaches. The characteristics of flow and solution transport were further investigated in the models by in-vitro and numerical simulations.
     This work consists of three sections as follows:
     Three-dimensional computer reconstruction of complex blood vessels. A computer model of the circle of Willis was first reconstructed based on medical images using the commercial software SIMPLEWARE. Moreover, an algorithm for image processing and structured hexahedral mesh generation was developed and successfully applied in the reconstruction of bifurcated vessels and a rat kidney, which provides a valuable image-based modeling method for analyzing hemodynamics in vasculars with real geometries.
     Development of in-vitro patient-specific models. An approach for making a transparent silicone phantom containing a vessel network was developed. The real geometric in-vitro model was manufactured by stacking plexiglas templates and combining different thermal physical and optical materials. The developed approach is low-costed, fast, and valid compared to three-dimensional printers.
     Experimental and numerical validations of the flow characteristics in the circle of Willis. In-vitro perfusion experimental platform was made and the methods for measuring pressure, flow, and temperature were confirmed by using a U-tube ultrasound phantom. The flow characteristics in the circle of Willis were explored by a particle image velocimetry (PFV) visualization experiment whose tracer particles are made of special dyed resin. Meanwhile the solution transport characteristics in the circle of Willis were investigated by the injection of ink solution from the left and right carotid artery and the basilar artery.
     The results of the solution experiment show that different feeding arteries have different roles in the cerebral circulation. The solution from the internal carotid artery is mainly distributed to the regions of the middle cerebral artery, anterior cerebral artery, and ophthalmic artery, whereas the solution from the basilar artery can be distributed to the whole circle of Willis. On the other hand, the supplied regions of the solution are changed under the same experiment when an aneurysm appears in the circle of Willis.
     The result of PIV experiment further show that the flows in the left and right side of the circle of Willis become more balanced except those in the bilateral ophthalmic arteries after the aneurysm occurs. It is found that the average velocities in the three communicating arteries increase significantly in the circle of Willis with an aneurysm, which means there are more flows from the communicating arteries to compensate the flow in the collateral side. Moreover, the occurrence of the aneurysm causes the flow difference in the left and right ophthalmic artery to become larger. It is interesting to note that there exists back-flow in the posterior communicating arteries during every cycle of the pump in the two vessel structures.
     These results suggest that the characteristics of the flow and mass transfer in the entire circle of Willis are significantly changed with the occurrence of the aneurysm in the carotid-ophthalmic artery, thus the distribution of blood flow to the brain tissue will be changed. This study provides more knowledge about the effect of aneurysm on the cerebral circulation and will be helpful for knowing the mechanism of its occurrence.
引文
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