内淋巴积水豚鼠前庭器的形态变化及外膜半规管力学建模与分析
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摘要
人和哺乳动物的内耳由骨迷路和膜迷路两套复杂管道组成,其中膜迷路内充满内淋巴液,并含有位觉感受器(前庭器)和听觉感受器(耳蜗)。前庭器由三个半规管、椭圆囊和球囊组成,感受自身运动状态及头部在空间位置,并与身体的平衡调节有关。半规管是头部角加速度感受器,机械刺激是前庭器感知头部位置变化的始动因素。内淋巴积水(endolymphatic hydrops, EH)是由于各种原因导致内淋巴产生过多或吸收障碍引起的内耳膜迷路内淋巴液增多,又称膜迷路积水。梅尼埃病(Meniere's disease, MD)是一种特发性膜迷路积水综合征,临床表现为反复发作性眩晕,感音神经性听力下降,耳鸣和耳胀闷感。一般认为其病因和发病机制与EH密切相关。EH可引起蜗管、球囊、椭圆囊的膨胀。蜗管的膨胀可能改变基底膜振动的行波方式,影响MD患者的听力,而半规管、椭圆囊的膨胀是否影响膜半规管内淋巴液与壶腹帽的相互作用,导致MD患者产生前庭症状,尚未见文献报道。
本研究在光镜和电镜下观察正常和EH对豚鼠前庭终器的形态学影响,发现豚鼠外膜半规管壶腹嵴毛细胞纤毛束(hair cell bundles, HBC)的损伤存在明显的区域差别,外半规管壶腹嵴嵴顶和椭圆囊斑微纹处的HBC损伤最为严重。在Micro-CT图像清晰显示前庭器膜性壁的基础上进行三维(three-dimensional,3D)重建,观察豚鼠前庭器结构的形态、空间位置及相互毗邻关系；测量外膜半规管和椭圆囊在垂直于流体流动方向横断面的管径,结果显示外膜半规管横断面为椭圆形,其长径和短径之比恒定；椭圆囊和壶腹长径与短径之比明显大于外膜半规管。EH豚鼠椭圆囊和外膜壶腹的管径明显增大,而外膜半规管管径无明显改变,该模型为研究内淋巴液在外膜半规管和椭圆囊的流动特征、内淋巴液与壶腹嵴的相互作用提供了形态几何参数。
借助逆向工程软件Geomagic Studio对MIMICS重建输出的3D表面模型进行去除毛噪、修补和曲面优化等处理,分别建立前庭膜迷路、外膜半规管和椭圆囊的三维几何模型。根据外膜半规管和椭圆囊各部分的管径测量结果,建立正常和EH豚鼠外膜半规管和椭圆囊二维(two-dimensional,2D)有限元模型,分析正常和EH豚鼠头部旋转过程中内淋巴液与壶腹帽的流固耦合作用,结果显示由于内淋巴液的惯性作用而滞后于半规管的运动而引起壶腹帽的变形,产生的位移和剪切应变有所不同。提示壶腹帽剪切应变可能是带动壶腹嵴毛细胞纤毛偏转的主要因素,EH豚鼠椭圆囊和半规管壶腹的膨大导致壶腹帽剪切应变的增加或振幅增大,可能是EH豚鼠壶腹嵴嵴顶HBC损伤的重要原因之一
本研究探讨EH对豚鼠前庭器形态和功能的影响,利用外膜半规管2D有限元模型,模拟EH豚鼠在头部水平旋转运动过程中,内淋巴液和壶腹帽的流固耦合作用,分析外膜半规管壶腹嵴HBC受损的力学因素。EH后豚鼠球囊、椭圆囊和膜壶腹存在不同程度的膨胀,而膜半规管未见明显改变。EH对豚鼠外半规管壶腹嵴HBC的损伤在嵴顶最为明显。壶腹帽的最大剪切应变集中在壶腹嵴嵴顶附近,EH时明显增加。EH时椭圆囊和壶腹的膨胀,影响了内淋巴液对壶腹帽的作用,壶腹嵴嵴顶附近壶腹帽的剪切应变的增大或振幅增加,可能导致此处HBC的损伤。上述研究结果有助于理解EH发生发展过程中前庭器损伤的力学因素,加深对前庭的病理生理过程的认识。
The labyrinth in the inner ear consists of the same membranous labyrinth within a bony labyrinth construction. Both tubes are fluid-filled, with endolymph in the membranous labyrinth. The vestibular organ and cochlea are located in the labyrinth. The vestibular organ contains three semicircular canals (SCCs), utricle and saccule. It is the primary organ of equilibrium and plays a major role in the subjective sensation of motion and spatial orientation. Vestibular organ are mechanoreceptors, SCCS sense angular acceleration. Endolymphatic hydrops (EH), also known as labyrinthine hydrops, is excessive endolymphy in the inner membranous labyrinth causing by a large number of factors. The factors include excessive endolymph production, decreased endolymph absorption by the endolymphatic sac. Meniere's disease (MD) is an idiopathic endolymphatic hydrops of the inner ear characterized by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The cause of MD remains unknown but is likely to be associated with EH. Mechanical alteration of the traveling waves by hydrops may explain some aspects of cochlear dysfunction. There is no related article about the relationship between dilation of vestibular membranous labyrinth and the vestibular manifestations.
Morphological changes of EH induced experimentally with emphasis on vestibular organ were observed under optical and electron microscope. The damage of hair cell stereocilia was more severe at the top of lateral crista ampulla and utricle striola than other parts in vestibular organs. Through a method of contrast enhancement based on en bloc staining in osmium tetroxide (OsO4) and the application of micro-computed tomography (Micro-CT), the accurate three-dimensional (3D) structures were reconstructed to reveal the shape, spatial location and contiguity of guinea pigs'membranous vestibular labyrinth. The results show that the transverse sections of lateral semicircular duct are ellipses with a constant ratio between minor and major axis diameter along the endolymph flow. The ratio between minor and major axis diameter in utricle and ampulla are greater than that in lateral semicircular duct. The dilation of the membrane was found to involve both the utricle and the ampulla in guinea pigs with EH. The study supplied geometric parameters for investigating the endolymph flow characteristics and the interaction of endolymph and cupula.
The reconstructed3D membranous vestibular labyrinths were optimized through removing spikes, filling cavities, and optimizing surface using the reverse engineering software Geomagic Studio. The optimized3D models include whole membranous vestibular labyrinths and single lateral semicircular duct. The two dimensional (2D) lateral semicircular duct finite element models (FEM) of guinea pigs with and without EH were built based on the3D models to analyze the fluid-structure interaction of endolymph and cupula. The lagged flow fluid of the endolymph in the lateral semicircular duct leads to the cupular deflection. The maximum cupular displacement locates the center of the cupula, while the maximum shear strain occurs near the top surface of the crista. The maximum cupular displacement and shear strain in EH model are greater than that in normal model. The greater shear stain of the cupula in EH model induced by dilation of cupula and utricle may cause the damage of the hair cell cilia.
The research discussed the effect of EH on the vestibular organ, simulated the interaction of the endolymph and cupula during head rotation motion based on the2D FEM of lateral semicircular duct with and without EH and analyzed the mechanical factors causing injury of the hair cell cilia. The dilatation of the membranous vestibular labyrinths is particularly in the saccule, utricle and membranous ampulla, but not in the semicircular duct. The cilia of lateral crista ampullaris at the top are damaged more severely than those at other parts. The maximum shear strain of cupula occurs near the top surface of the crista. The greater maximum cupular displacement and shear strain in EH maybe one of the reasons to damage of the hair cell cilia. The research is help to understand the mechanical role during the progress of EH and the cognition for the vestibular pathophysiology.
本研究在光镜和电镜下观察正常和EH对豚鼠前庭终器的形态学影响,发现豚鼠外膜半规管壶腹嵴毛细胞纤毛束(hair cell bundles, HBC)的损伤存在明显的区域差别,外半规管壶腹嵴嵴顶和椭圆囊斑微纹处的HBC损伤最为严重。在Micro-CT图像清晰显示前庭器膜性壁的基础上进行三维(three-dimensional,3D)重建,观察豚鼠前庭器结构的形态、空间位置及相互毗邻关系；测量外膜半规管和椭圆囊在垂直于流体流动方向横断面的管径,结果显示外膜半规管横断面为椭圆形,其长径和短径之比恒定；椭圆囊和壶腹长径与短径之比明显大于外膜半规管。EH豚鼠椭圆囊和外膜壶腹的管径明显增大,而外膜半规管管径无明显改变,该模型为研究内淋巴液在外膜半规管和椭圆囊的流动特征、内淋巴液与壶腹嵴的相互作用提供了形态几何参数。
借助逆向工程软件Geomagic Studio对MIMICS重建输出的3D表面模型进行去除毛噪、修补和曲面优化等处理,分别建立前庭膜迷路、外膜半规管和椭圆囊的三维几何模型。根据外膜半规管和椭圆囊各部分的管径测量结果,建立正常和EH豚鼠外膜半规管和椭圆囊二维(two-dimensional,2D)有限元模型,分析正常和EH豚鼠头部旋转过程中内淋巴液与壶腹帽的流固耦合作用,结果显示由于内淋巴液的惯性作用而滞后于半规管的运动而引起壶腹帽的变形,产生的位移和剪切应变有所不同。提示壶腹帽剪切应变可能是带动壶腹嵴毛细胞纤毛偏转的主要因素,EH豚鼠椭圆囊和半规管壶腹的膨大导致壶腹帽剪切应变的增加或振幅增大,可能是EH豚鼠壶腹嵴嵴顶HBC损伤的重要原因之一
本研究探讨EH对豚鼠前庭器形态和功能的影响,利用外膜半规管2D有限元模型,模拟EH豚鼠在头部水平旋转运动过程中,内淋巴液和壶腹帽的流固耦合作用,分析外膜半规管壶腹嵴HBC受损的力学因素。EH后豚鼠球囊、椭圆囊和膜壶腹存在不同程度的膨胀,而膜半规管未见明显改变。EH对豚鼠外半规管壶腹嵴HBC的损伤在嵴顶最为明显。壶腹帽的最大剪切应变集中在壶腹嵴嵴顶附近,EH时明显增加。EH时椭圆囊和壶腹的膨胀,影响了内淋巴液对壶腹帽的作用,壶腹嵴嵴顶附近壶腹帽的剪切应变的增大或振幅增加,可能导致此处HBC的损伤。上述研究结果有助于理解EH发生发展过程中前庭器损伤的力学因素,加深对前庭的病理生理过程的认识。
The labyrinth in the inner ear consists of the same membranous labyrinth within a bony labyrinth construction. Both tubes are fluid-filled, with endolymph in the membranous labyrinth. The vestibular organ and cochlea are located in the labyrinth. The vestibular organ contains three semicircular canals (SCCs), utricle and saccule. It is the primary organ of equilibrium and plays a major role in the subjective sensation of motion and spatial orientation. Vestibular organ are mechanoreceptors, SCCS sense angular acceleration. Endolymphatic hydrops (EH), also known as labyrinthine hydrops, is excessive endolymphy in the inner membranous labyrinth causing by a large number of factors. The factors include excessive endolymph production, decreased endolymph absorption by the endolymphatic sac. Meniere's disease (MD) is an idiopathic endolymphatic hydrops of the inner ear characterized by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The cause of MD remains unknown but is likely to be associated with EH. Mechanical alteration of the traveling waves by hydrops may explain some aspects of cochlear dysfunction. There is no related article about the relationship between dilation of vestibular membranous labyrinth and the vestibular manifestations.
Morphological changes of EH induced experimentally with emphasis on vestibular organ were observed under optical and electron microscope. The damage of hair cell stereocilia was more severe at the top of lateral crista ampulla and utricle striola than other parts in vestibular organs. Through a method of contrast enhancement based on en bloc staining in osmium tetroxide (OsO4) and the application of micro-computed tomography (Micro-CT), the accurate three-dimensional (3D) structures were reconstructed to reveal the shape, spatial location and contiguity of guinea pigs'membranous vestibular labyrinth. The results show that the transverse sections of lateral semicircular duct are ellipses with a constant ratio between minor and major axis diameter along the endolymph flow. The ratio between minor and major axis diameter in utricle and ampulla are greater than that in lateral semicircular duct. The dilation of the membrane was found to involve both the utricle and the ampulla in guinea pigs with EH. The study supplied geometric parameters for investigating the endolymph flow characteristics and the interaction of endolymph and cupula.
The reconstructed3D membranous vestibular labyrinths were optimized through removing spikes, filling cavities, and optimizing surface using the reverse engineering software Geomagic Studio. The optimized3D models include whole membranous vestibular labyrinths and single lateral semicircular duct. The two dimensional (2D) lateral semicircular duct finite element models (FEM) of guinea pigs with and without EH were built based on the3D models to analyze the fluid-structure interaction of endolymph and cupula. The lagged flow fluid of the endolymph in the lateral semicircular duct leads to the cupular deflection. The maximum cupular displacement locates the center of the cupula, while the maximum shear strain occurs near the top surface of the crista. The maximum cupular displacement and shear strain in EH model are greater than that in normal model. The greater shear stain of the cupula in EH model induced by dilation of cupula and utricle may cause the damage of the hair cell cilia.
The research discussed the effect of EH on the vestibular organ, simulated the interaction of the endolymph and cupula during head rotation motion based on the2D FEM of lateral semicircular duct with and without EH and analyzed the mechanical factors causing injury of the hair cell cilia. The dilatation of the membranous vestibular labyrinths is particularly in the saccule, utricle and membranous ampulla, but not in the semicircular duct. The cilia of lateral crista ampullaris at the top are damaged more severely than those at other parts. The maximum shear strain of cupula occurs near the top surface of the crista. The greater maximum cupular displacement and shear strain in EH maybe one of the reasons to damage of the hair cell cilia. The research is help to understand the mechanical role during the progress of EH and the cognition for the vestibular pathophysiology.
引文
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