本文選題：人工中耳 + 耳蝸逆向驅(qū)動(dòng)��； 參考：《復(fù)旦大學(xué)》2013年博士論文

【摘要】：聽覺是人類感知世界不可缺少的感知方式之一。正常情況下由聲源振動(dòng)引起空氣振動(dòng)產(chǎn)生的疏密波,經(jīng)外耳道通過鼓膜進(jìn)入中耳,引起聽骨鏈振動(dòng),再通過卵圓窗進(jìn)入內(nèi)耳,振動(dòng)前庭階內(nèi)的外淋巴液,使振動(dòng)自前庭階通過蝸頂?shù)奈伩讉鬟f至鼓階,最后使圓窗振動(dòng),同時(shí),兩階的外淋巴壓力發(fā)生變化導(dǎo)致基底膜振動(dòng),刺激內(nèi)外毛細(xì)胞進(jìn)而激勵(lì)聽神經(jīng)末梢產(chǎn)生聽覺神經(jīng)沖動(dòng)。人工中耳是通過將聲波的能量轉(zhuǎn)換成機(jī)械振動(dòng),并借助附著在耳內(nèi)可振動(dòng)部位(如聽骨鏈)或耳蝸(如前庭窗、蝸窗)上的中耳植入體,將振動(dòng)傳入內(nèi)耳而產(chǎn)生聽覺的裝置。其與聽骨鏈連接后可代替部分或全部聽骨鏈的作用,有助于中重度感音性或混合性聾患者改善聽力。然而,部分外耳道、昕骨鏈或鼓室異常(如先天性中外耳畸形、鐙骨固定等)的中重度傳導(dǎo)性或混合性聾病患者,由于中耳手術(shù)失敗或難以手術(shù)、助聽器佩戴困難等原因,導(dǎo)致人工中耳裝置難以經(jīng)卵圓窗傳音途徑有效地將聲能傳遞入內(nèi)耳。因此對(duì)于此類患者,不少學(xué)者采用圓窗途徑人工中耳來改善聽力。當(dāng)聲波經(jīng)圓窗途徑傳入耳蝸后,首先將振動(dòng)傳遞至鼓階的外淋巴液,然后經(jīng)蝸頂至前庭階,引起相應(yīng)的卵圓窗振動(dòng),在兩階間沿著耳蝸的不同部位產(chǎn)生壓力梯度,使基底膜振動(dòng)而感音。所以在本研究中我們將卵圓窗途徑給聲稱之為“正向途徑”或“耳蝸正向驅(qū)動(dòng)”(Forward Driving),而如上述這種圓窗途徑傳音的方式稱之為“逆向途徑”或“耳蝸逆向驅(qū)動(dòng)”(Reverse Driving)。 自上世紀(jì)50年代起就有學(xué)者開始通過動(dòng)物實(shí)驗(yàn)研究耳蝸的逆向驅(qū)動(dòng),至今已有不少學(xué)者致力于該領(lǐng)域的研究。通過動(dòng)物實(shí)驗(yàn),人們發(fā)現(xiàn)耳蝸正向驅(qū)動(dòng)和逆向驅(qū)動(dòng)均可產(chǎn)生相似的耳蝸電位、聽性腦干反應(yīng)、聽神經(jīng)動(dòng)作電位以及跨蝸階壓力差。而且自2006年起圓窗途徑人工中耳開始應(yīng)用于臨床研究。據(jù)文獻(xiàn)報(bào)道,其臨床效果及短期隨訪結(jié)果尚可,對(duì)患者的殘余聽力尚未發(fā)現(xiàn)明顯不利影響,植入裝置激活后言語識(shí)別率、純音聽閾等較術(shù)前均有明顯提高。但是,耳蝸逆向驅(qū)動(dòng)畢竟不是一個(gè)正常的生理傳音過程,而且由于耳蝸內(nèi)含前庭階、鼓階、蝸管、前庭膜以及基底膜,對(duì)于基底膜來說耳蝸并不是一個(gè)對(duì)稱的結(jié)構(gòu),所以我們認(rèn)為,正向和逆向途徑之間的區(qū)別不應(yīng)僅局限于相反的振動(dòng)傳導(dǎo),或者說,兩者對(duì)于基底膜的振動(dòng)效率而言可能并不是等效的。 本文使用實(shí)驗(yàn)研究和有限元模擬分析兩種方法對(duì)耳蝸正逆向驅(qū)動(dòng)的傳聲效率進(jìn)行了評(píng)估。 在實(shí)驗(yàn)研究中,我們使用8只成年健康豚鼠,深度麻醉后,迅速斷頭取出聽泡,自聽泡后下壁打開直徑2-3mm的小孔,然后在耳蝸底轉(zhuǎn)鼓階部位使用電鉆打開一直徑約為0.5～0.8mm的小孔,暴露基底膜,將一顆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膠封閉耳蝸及聽泡開孔。耳蝸正向驅(qū)動(dòng)時(shí),我們?cè)谕舛纼?nèi)距鼓膜2mm處,使用微型揚(yáng)聲器施加80dB SPL的聲壓,頻率范圍1-40kHz。隨后利用激光多普勒測(cè)振技術(shù),測(cè)量耳蝸正向驅(qū)動(dòng)下的砧骨長(zhǎng)突、基底膜的振動(dòng)。在進(jìn)行耳蝸逆向驅(qū)動(dòng)前,為了在豚鼠模型中實(shí)現(xiàn)耳蝸的逆向驅(qū)動(dòng),我們自制一套圓窗振子線圈驅(qū)動(dòng)系統(tǒng),并成功地經(jīng)逆向途徑驅(qū)動(dòng)基底膜產(chǎn)生有效的振動(dòng)。同時(shí),為了使正逆向振動(dòng)更有可比性,我們首先以1-40kHz的交流電驅(qū)動(dòng)線圈,測(cè)量砧骨長(zhǎng)突末端的振動(dòng),并以正向驅(qū)動(dòng)時(shí)的結(jié)果作為參照,調(diào)整線圈驅(qū)動(dòng)電流大小,間接調(diào)節(jié)磁性振子的振動(dòng)強(qiáng)度,使得逆向驅(qū)動(dòng)時(shí)砧骨長(zhǎng)突末端的振動(dòng)與正向驅(qū)動(dòng)時(shí)盡可能地相近。然后保持驅(qū)動(dòng)電流及其它實(shí)驗(yàn)設(shè)置不變,僅調(diào)整激光束,進(jìn)行基底膜及磁性振子振動(dòng)的測(cè)量。完成測(cè)量后,我們?yōu)榱藢?duì)兩種途徑下的傳聲效率進(jìn)行評(píng)估,進(jìn)一步計(jì)算耳蝸正逆向驅(qū)動(dòng)下基底膜底轉(zhuǎn)的耳蝸增益,并進(jìn)行比較。 在有限元數(shù)值模擬中,我們使用現(xiàn)有的人耳有限元模型,該模型包括外耳道、中耳、中耳腔空氣、中耳韌帶肌腱、耳蝸(內(nèi)含前庭階、鼓階和蝸管,無Corti器)以及淋巴液等結(jié)構(gòu)。正向驅(qū)動(dòng)時(shí),在模型的外耳道中,據(jù)鼓膜2mm處加載90dB SPL的聲壓,頻率范圍100Hz-10kHz。逆向驅(qū)動(dòng)時(shí),模擬兩種不同尺寸的圓窗振子,均安放于中耳側(cè)圓窗膜中央。1號(hào)振子較大,截面積1mm2,高1.2mm,質(zhì)量7mg,與圓窗的面積比為0.47：1；2號(hào)振子較小,截面積0.314mm2,高1.2mm,質(zhì)量2.2mg,為與圓窗的面積比為0.14：1。隨后將一個(gè)大小為0.05mN的軸向驅(qū)動(dòng)力加載在圓窗振子的游離端,頻率范圍100Hz-10kHz。完成以上設(shè)定后,對(duì)3個(gè)模型進(jìn)行諧響應(yīng)分析,并分別提取不同情況下鼓膜、鐙骨底板、圓窗膜中心點(diǎn)的軸向振幅,以及不同頻率下基底膜不同位置的振幅。同時(shí),為了提高正逆向的可比性,以及與豚鼠實(shí)驗(yàn)的可比性,還分別計(jì)算不同情況下的耳蝸輸入阻抗,以及基底膜底轉(zhuǎn)的耳蝸增益。 實(shí)驗(yàn)研究結(jié)果與有限元數(shù)值模擬結(jié)果基本一致。結(jié)果顯示,自制圓窗振子系統(tǒng)運(yùn)行穩(wěn)定,能夠從逆向途徑驅(qū)動(dòng)基底膜產(chǎn)生有效振動(dòng)；基底膜的特征頻率在正向和逆向驅(qū)動(dòng)下相同,實(shí)驗(yàn)中均為15kHz左右；正向驅(qū)動(dòng)較逆向驅(qū)動(dòng)具有較低的耳蝸輸入阻抗,較高的耳蝸增益,所以正向驅(qū)動(dòng)具有較高的傳聲效率；逆向驅(qū)動(dòng)時(shí),使用較大的振子,可以降低逆向驅(qū)動(dòng)時(shí)的耳蝸輸入阻抗,從而產(chǎn)生較大的耳蝸增益,提高傳聲效率。以上結(jié)果提示,臨床上,在植入逆向驅(qū)動(dòng)人工中耳前,事先切除殘余、廢用或硬化的聽骨鏈,可有效減少逆向途徑下耳蝸的輸入阻抗,以取得更好的傳音效果。同時(shí),應(yīng)適當(dāng)增加振子的體積,一方面可以產(chǎn)生更加有效的基底膜振動(dòng),另一方面,可以增強(qiáng)振子的電磁感應(yīng),提高振動(dòng)強(qiáng)度,有效改善振子的頻率響應(yīng)。 本文通過使用自制的圓窗振子線圈驅(qū)動(dòng)系統(tǒng),在豚鼠耳蝸上成功實(shí)現(xiàn)逆向驅(qū)動(dòng),并利用激光多普勒技術(shù),首次實(shí)際測(cè)量耳蝸逆向驅(qū)動(dòng)下的基底膜振動(dòng)。其結(jié)果有助于闡明耳蝸逆向驅(qū)動(dòng)的機(jī)制,并為評(píng)估其傳音效率提供有效的方法,為臨床圓窗途徑人工中耳植入的改進(jìn)提供依據(jù)。
[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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R318.18

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