Improving an animal model of human hearing loss: quantifying risks associated with common otolaryngology procedures

项目总结/摘要 许多外科手术，包括旨在恢复听力的耳科手术，涉及大量的听力障碍。 中耳和内耳的操作。特别是人工耳蜗植入物（CI）， 越来越多地适用于有一些残余听觉的患者，包括直接操纵 内耳的内容物不幸的是，这些患者中高达50%的人失去了他们的残余听觉， 所有CI患者中有相当大比例的患者在术后一段时间或之后立即经历平衡功能障碍。 手术几项旨在确定即刻听力损失原因的研究表明， 虽然CI电极的存在基本上不改变耳蜗中的声音传输，但是高水平的 在插入期间在耳蜗中产生瞬变。这些颅内压（PIC）瞬变可 显示峰值压力超过170 dB SPL峰值等效耳道SPL（PEAC），因此可能导致噪音- 听力或前庭功能丧失。这些研究是第一个确定PIC瞬变存在的研究， 未能确定这些风险的来源和风险。本提案的目的是 使用两种技术克服这些先前的缺点。首先（目标1），我们将进一步表征PIC 在尸体样本中CI手术期间的瞬变。PIC测量将在 插入、操作和移除CI电极，以量化产生的PIC瞬变的数量，以及 与CI电极制造商、几何结构和插入方式（即，使用鞘管或 管心针或通过镊子）。将在一个子集中使用实时荧光透视成像研究PIC瞬变的来源 将PIC事件与耳蜗中的电极位置相关联。第二（目标2）， 将在龙猫中确定这些PIC瞬变引起的听力损失。目标1中记录的PIC瞬变将是 转换成声刺激，产生相同的脑内暴露在栗鼠使用最近的 在龙猫和人类的内耳声音传输之间的量化关系。这 技术，这将产生声音刺激，产生PIC在龙猫是相同的PIC在 在CI手术期间观察到的人类耳蜗，需要使用两个最近的创新：1）表征这种 关系，以及2）开发能够产生必要的高水平声学的扬声器 刺激。此后的实验遵循标准的噪声暴露协议，其中生理测量 在暴露于噪声之前和暴露于噪声之后的几个时间点评估动物的听力，以评估结果。 永久性听力损失因此，这些测量将提供听力损失的定量估计。 预期暴露于CI手术期间产生的PIC瞬变，可能导致电极改进 设计和手术技术。因此，该提案将开发和验证用于评估的动物模型。 人类噪音导致听力损失的风险。此外，由于PIC可以针对任何源测量， 刺激内耳，这项建议开发了一种技术，可用于评估噪音引起的听力 非传统（非空气传导）噪声源的损失风险。

Project Summary/Abstract Many surgical procedures, including otological procedures intended to restore hearing, involve substantial manipulation of components of the middle and inner ear. In particular cochlear implants (CIs), which are increasingly indicated for patients with some residual acoustic hearing, involves direct manipulation of the contents of the inner ear. Unfortunately, up to ~50% of these patients lose their residual acoustic hearing, and a substantial proportion of all CI patients experience balance dysfunction either immediately or some time after surgery. Several studies aimed at determining the cause of the immediate hearing loss have suggested that while the presence of a CI electrode does not substantially alter sound transmission in the cochlea, high-level transients are generated in the cochlea during insertion. These intracochlear pressure (PIC) transients can show peak pressures in excess of 170 dB SPL peak equivalent ear canal SPL (PEAC), thus could cause noise- induced hearing or vestibular loss. These studies were the first to identify the presence of PIC transients, but failed to identify the sources and the risks to hearing from these exposures. The goal of this proposal is to overcome these previous shortcomings using two techniques. First (aim 1), we will further characterize PIC transients during CI surgery in cadaveric human specimens. PIC measurements will be conducted during insertion, manipulation, and removal of CI electrodes to quantify the number of PIC transients generated, and correlate with features such as CI electrode manufacturer, geometry, and insertion style (i.e. with a sheath or stylet or via forceps). The source of PIC transients will be investigated with live fluoroscopic imaging in a subset of these experiments to correlate PIC events with electrode position in the cochlea. Second (aim 2), the risk of hearing loss from these PIC transients will be determined in chinchillas. PIC transients recorded in aim 1 will be translating into acoustic stimuli that produce identical intracochlear exposures in chinchilla using the recently quantified relationship between sound transmission into the inner ear in chinchillas and humans. This technique, which will generate acoustic stimuli that produce PIC in chinchillas that are identical to the PIC in human cochlea observed during CI surgery, requires use of two recent innovations:1) characterization of this relationship, and 2) development of a loudspeaker capable of generating the necessary high-level acoustic stimuli. The experiments thereafter follow a standard noise-exposure protocol in which physiological measures of animal hearing are assessed before, and at several time points after noise exposure to assess the resulting permanent hearing loss. These measurements will thus provide a quantitative estimate of the hearing loss expected from exposure to PIC transients generated during CI surgery that may lead to improved electrode design and surgical techniques. This proposal will thereby develop and validate an animal model for assessing human noise induced hearing loss risk. Furthermore, since PIC may be measured for any source that stimulates the inner ear, this proposal develops a technique that may be used to assess noise-induced hearing loss risk for non-traditional (non-air-conducted) noise sources.