耳蜗正逆向驱动传声效率的实验研究和数值模拟

发布时间：2018-06-08 23:37

本文选题：人工中耳 + 耳蜗逆向驱动　；参考：《复旦大学》2013年博士论文

【摘要】：听觉是人类感知世界不可缺少的感知方式之一。正常情况下由声源振动引起空气振动产生的疏密波,经外耳道通过鼓膜进入中耳,引起听骨链振动,再通过卵圆窗进入内耳,振动前庭阶内的外淋巴液,使振动自前庭阶通过蜗顶的蜗孔传递至鼓阶,最后使圆窗振动,同时,两阶的外淋巴压力发生变化导致基底膜振动,刺激内外毛细胞进而激励听神经末梢产生听觉神经冲动。人工中耳是通过将声波的能量转换成机械振动,并借助附着在耳内可振动部位(如听骨链)或耳蜗(如前庭窗、蜗窗)上的中耳植入体,将振动传入内耳而产生听觉的装置。其与听骨链连接后可代替部分或全部听骨链的作用,有助于中重度感音性或混合性聋患者改善听力。然而,部分外耳道、昕骨链或鼓室异常(如先天性中外耳畸形、镫骨固定等)的中重度传导性或混合性聋病患者,由于中耳手术失败或难以手术、助听器佩戴困难等原因,导致人工中耳装置难以经卵圆窗传音途径有效地将声能传递入内耳。因此对于此类患者,不少学者采用圆窗途径人工中耳来改善听力。当声波经圆窗途径传入耳蜗后,首先将振动传递至鼓阶的外淋巴液,然后经蜗顶至前庭阶,引起相应的卵圆窗振动,在两阶间沿着耳蜗的不同部位产生压力梯度,使基底膜振动而感音。所以在本研究中我们将卵圆窗途径给声称之为“正向途径”或“耳蜗正向驱动”(Forward Driving),而如上述这种圆窗途径传音的方式称之为“逆向途径”或“耳蜗逆向驱动”(Reverse Driving)。自上世纪50年代起就有学者开始通过动物实验研究耳蜗的逆向驱动,至今已有不少学者致力于该领域的研究。通过动物实验,人们发现耳蜗正向驱动和逆向驱动均可产生相似的耳蜗电位、听性脑干反应、听神经动作电位以及跨蜗阶压力差。而且自2006年起圆窗途径人工中耳开始应用于临床研究。据文献报道,其临床效果及短期随访结果尚可,对患者的残余听力尚未发现明显不利影响,植入装置激活后言语识别率、纯音听阈等较术前均有明显提高。但是,耳蜗逆向驱动毕竟不是一个正常的生理传音过程,而且由于耳蜗内含前庭阶、鼓阶、蜗管、前庭膜以及基底膜,对于基底膜来说耳蜗并不是一个对称的结构,所以我们认为,正向和逆向途径之间的区别不应仅局限于相反的振动传导,或者说,两者对于基底膜的振动效率而言可能并不是等效的。本文使用实验研究和有限元模拟分析两种方法对耳蜗正逆向驱动的传声效率进行了评估。在实验研究中,我们使用8只成年健康豚鼠,深度麻醉后,迅速断头取出听泡,自听泡后下壁打开直径2-3mm的小孔,然后在耳蜗底转鼓阶部位使用电钻打开一直径约为0.5～0.8mm的小孔,暴露基底膜,将一颗反光微珠放置于基底膜的中央,完成以上操作后使用玻璃薄片及牙科胶封闭耳蜗及听泡开孔。耳蜗正向驱动时,我们在外耳道内距鼓膜2mm处,使用微型扬声器施加80dB SPL的声压,频率范围1-40kHz。随后利用激光多普勒测振技术,测量耳蜗正向驱动下的砧骨长突、基底膜的振动。在进行耳蜗逆向驱动前,为了在豚鼠模型中实现耳蜗的逆向驱动,我们自制一套圆窗振子线圈驱动系统,并成功地经逆向途径驱动基底膜产生有效的振动。同时,为了使正逆向振动更有可比性,我们首先以1-40kHz的交流电驱动线圈,测量砧骨长突末端的振动,并以正向驱动时的结果作为参照,调整线圈驱动电流大小,间接调节磁性振子的振动强度,使得逆向驱动时砧骨长突末端的振动与正向驱动时尽可能地相近。然后保持驱动电流及其它实验设置不变,仅调整激光束,进行基底膜及磁性振子振动的测量。完成测量后,我们为了对两种途径下的传声效率进行评估,进一步计算耳蜗正逆向驱动下基底膜底转的耳蜗增益,并进行比较。在有限元数值模拟中,我们使用现有的人耳有限元模型,该模型包括外耳道、中耳、中耳腔空气、中耳韧带肌腱、耳蜗(内含前庭阶、鼓阶和蜗管,无Corti器)以及淋巴液等结构。正向驱动时,在模型的外耳道中,据鼓膜2mm处加载90dB SPL的声压,频率范围100Hz-10kHz。逆向驱动时,模拟两种不同尺寸的圆窗振子,均安放于中耳侧圆窗膜中央。1号振子较大,截面积1mm2,高1.2mm,质量7mg,与圆窗的面积比为0.47：1；2号振子较小,截面积0.314mm2,高1.2mm,质量2.2mg,为与圆窗的面积比为0.14：1。随后将一个大小为0.05mN的轴向驱动力加载在圆窗振子的游离端,频率范围100Hz-10kHz。完成以上设定后,对3个模型进行谐响应分析,并分别提取不同情况下鼓膜、镫骨底板、圆窗膜中心点的轴向振幅,以及不同频率下基底膜不同位置的振幅。同时,为了提高正逆向的可比性,以及与豚鼠实验的可比性,还分别计算不同情况下的耳蜗输入阻抗,以及基底膜底转的耳蜗增益。实验研究结果与有限元数值模拟结果基本一致。结果显示,自制圆窗振子系统运行稳定,能够从逆向途径驱动基底膜产生有效振动；基底膜的特征频率在正向和逆向驱动下相同,实验中均为15kHz左右；正向驱动较逆向驱动具有较低的耳蜗输入阻抗,较高的耳蜗增益,所以正向驱动具有较高的传声效率；逆向驱动时,使用较大的振子,可以降低逆向驱动时的耳蜗输入阻抗,从而产生较大的耳蜗增益,提高传声效率。以上结果提示,临床上,在植入逆向驱动人工中耳前,事先切除残余、废用或硬化的听骨链,可有效减少逆向途径下耳蜗的输入阻抗,以取得更好的传音效果。同时,应适当增加振子的体积,一方面可以产生更加有效的基底膜振动,另一方面,可以增强振子的电磁感应,提高振动强度,有效改善振子的频率响应。本文通过使用自制的圆窗振子线圈驱动系统,在豚鼠耳蜗上成功实现逆向驱动,并利用激光多普勒技术,首次实际测量耳蜗逆向驱动下的基底膜振动。其结果有助于阐明耳蜗逆向驱动的机制,并为评估其传音效率提供有效的方法,为临床圆窗途径人工中耳植入的改进提供依据。
[Abstract]:Hearing is one of the indispensable ways of perception in the human world. Under normal circumstances, the acoustic wave caused by the vibration of the sound source, through the ear canal, enters the middle ear through the tympanic membrane, causes the vibration of the ossicular chain, and then enters the inner ear through the oval window, and vibrates the external drenching liquid in the vestibule order, so that the vibration is transmitted from the vestibule step through the worm hole of the worm top. It is delivered to the drum stage and finally vibrates the round window. At the same time, the two order of the external lymphatic pressure changes the vibration of the basement membrane and stimulates the inner and outer hair cells to stimulate the auditory nerve to produce the auditory nerve impulse. The artificial middle ear is converted into mechanical vibration by the sound wave energy, and the vibration parts (such as the ossicular chain) or the cochlea are attached to the ear. An implant in the middle ear of a vestibule, a cochlear window, which moves the vibration into the inner ear and produces an auditory device. It is connected with the ossicular chain to replace some or all of the ossicular chain, and helps to improve hearing in patients with moderate or severe sensorineural or mixed hearing loss. However, some external auditory meatus, Xin bone chain or tympanic disorder (such as congenital middle ear malformation, stapes) Because of the failure of the middle ear surgery or the difficult operation of the middle ear surgery and the difficulty in wearing the hearing aid, the artificial middle ear device is difficult to transmit the sound energy into the inner ear effectively because of the failure of the middle ear operation or the difficulty in wearing the hearing aid. When the sound waves are introduced into the cochlea through a round window approach, the vibration is first transmitted to the lymph of the drum stage, and then through the cochlear top to the vestibule order, causing the corresponding oval window vibration. In the two order, the pressure gradient is produced along the different parts of the cochlea to make the basement membrane vibrate and sound. So in this study we put the oval window to claim that "positive" The way "or the cochlear forward drive" (Forward Driving) is referred to as the "reverse pathway" or "Reverse Driving" (Reverse Driving).
Since the 50s of last century, some scholars have begun to study the reverse drive of the cochlea through animal experiments. Many scholars have been devoted to the research in this field. Through animal experiments, it is found that the cochlear potential, auditory brainstem response, auditory action potential and cross worm pressure can be produced by the positive and reverse drive of the cochlea. It has been reported that the clinical effect and the short-term follow-up results are still available, and there is no obvious adverse effect on the residual hearing of the patients. The speech recognition rate and the pure tone threshold are obviously improved after the implantation, but the reverse driving of the cochlea has been improved. It is not a normal physiological sound process, and because the cochlea contains vestibule, drum, cochlear, vestibule, and basement membrane, the cochlea is not a symmetrical structure for the basement membrane, so we think the difference between the forward and reverse pathways should not be limited to the opposite vibration conduction, or, in other words, the two are to the base. The vibration efficiency of the membrane may not be equivalent.
In this paper, two methods are used to evaluate the sound transmission efficiency of the cochlear drive.
In the experimental study, we used 8 adult healthy guinea pigs. After deep anesthesia, we quickly broken the head out of the auditory bubble and opened the hole of the diameter 2-3mm from the lower wall of the auditory alveolus. Then we opened a small hole about 0.5 ~ 0.8mm in diameter with a electric drill in the drum stage of the cochlea, exposing the basement membrane and placing a reflective microsphere in the center of the basement membrane. After the above operation, the cochlea and the alveolar opening were closed with glass sheet and dental glue. When the cochlea was driven, we applied the micro loudspeaker to the sound pressure of the 80dB SPL in the outer auditory canal at 2mm, and the frequency range 1-40kHz. then used the laser Doppler vibration technique to measure the anvil long process and the basement membrane vibration under the cochlear forward drive. Before cochlear reverse driving, in order to achieve the reverse drive of the cochlea in the guinea pig model, we made a set of circular window oscillator coil drive system and successfully driven the basement membrane to produce effective vibration. At the same time, in order to make the positive reverse vibration more comparable, we first measure the anvil with the 1-40kHz alternating current drive coil. The vibration of the end of the long process of the bone and the result of the forward drive are taken as reference, adjusting the driving current of the coil and indirectly regulating the vibration intensity of the magnetic oscillator, so that the vibration of the long process end of the anvil is as close as possible when the reverse drive is driven. Then the driving current and other experimental settings are kept unchanged and the laser beam is adjusted only. The measurement of the vibration of the basement membrane and magnetic oscillator. After the measurement, we have evaluated the sound efficiency of the two ways and further calculated the cochlear gain of the basal membrane base of the cochlea, and compared it.
In the finite element numerical simulation, we use the existing human ear finite element model, which includes the external ear canal, the middle ear, the middle ear cavity air, the middle ear ligament, the cochlea (including the vestibule order, the drum and the cochlear tube, the no Corti) and the lymph structure. In the forward drive, the sound pressure of 90dB SPL is loaded at the tympanic membrane in the outer ear canal of the model, and the frequency of the acoustic pressure is loaded at the drum membrane. When the rate range 100Hz-10kHz. is reverse drive, two different sizes of circular window vibrators are simulated, and the center.1 vibrator is larger in the middle ear side round window film, the section area 1mm2, the high 1.2mm, the mass 7Mg, the area ratio of the round window is 0.47:1, the No. 2 oscillator is smaller, the section area 0.314mm2, the high 1.2mm, the mass 2.2mg, and the ratio of the area to the round window is 0.14:1. followed later. The axial driving force of a 0.05mN is loaded on the free end of the circular window vibrator. After the frequency range 100Hz-10kHz. is completed, the harmonic response analysis of the 3 models is carried out. The axial amplitude of the drum film, the stapes floor, the center point of the circular window film under different circumstances, and the amplitude of the different positions of the basement membrane at different frequencies are also extracted respectively. In order to improve the inverse comparability and the comparability with the guinea pig experiment, the cochlear input impedance in different cases and the cochlear gain of the basement membrane bottom are calculated respectively.
The experimental results are in agreement with the results of the finite element numerical simulation. The results show that the home-made circular window vibrator system operates steadily and can produce effective vibration from the reverse path to drive the basement membrane. The characteristic frequency of the basement membrane is the same as the 15kHz left right in the forward and reverse drive, and the forward drive is lower than the reverse drive. The input impedance of the cochlea, higher cochlear gain, so the forward drive has a higher transmission efficiency. When the reverse drive, the use of a larger vibrator can reduce the input impedance of the cochlea in the reverse drive, thus producing a larger cochlear gain and improving the efficiency of the sound transmission. The first removal of the residual, waste or hardened ossicular chain can effectively reduce the input impedance of the cochlea under the reverse path to achieve a better sound transmission effect. At the same time, the volume of the vibrator should be increased properly. On the one hand, more effective vibration of the basement membrane can be produced. On the other hand, it can increase the electromagnetic induction of the vibrator, improve the vibration intensity and effectively improve the vibration. The frequency response of the sub.
In this paper, the reverse drive in the cochlea of guinea pigs is successfully realized by using a self-made circular window oscillator coil drive system, and the vibration of the basement membrane under the reverse driving of the cochlea is measured by laser Doppler technique for the first time. The results are helpful to clarify the mechanism of the cochlea reverse driving and provide an effective method to evaluate the efficiency of its sound transmission. It provides a basis for improving the implantation of the middle ear through the round window.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R318.18

【共引文献】