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

改善人类听力损失的动物模型：量化与常见耳鼻喉科手术相关的风险

• 批准号: 10240682
• 负责人: Nathaniel Tussing Greene
• 金额: $ 15.55万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240682
• 关键词: Acoustic Nerve; Acoustics; Address; Air; Animal Model; Animals; Attention; Auditory; Auditory Brainstem Responses; Basilar Membrane; Bone Conduction; Cadaver; Cell Death; Chinchilla (genus); Cochlea; Cochlear Hearing Loss; Cochlear Implants; Cochlear implant procedure; Development; Device Designs; Devices; Disease; Ear; Electrodes; Elements; Equilibrium; Event; Excision; Exposure to; External auditory canal; Fluoroscopy; Forcep; Functional disorder; Future; Generations; Geometry; Goals; Growth; Hair Cells; Hearing; Histopathology; Human; Image; Implanted Electrodes; Impulsivity; Labyrinth; Lead; Liquid substance; Literature; Manufacturer Name; Mastoid process; Measurement; Measures; Mechanical Stimulation; Methodology; Methods; Motion; Noise; Noise-Induced Hearing Loss; Operative Surgical Procedures; Otolaryngologist; Otolaryngology; Otology; Outer Hair Cells; Pathway interactions; Patients; Physiological; Positioning Attribute; Prevalence; Procedures; Protocols documentation; Recommendation; Residual state; Risk; Risk Factors; Semicircular canal structure; Series; Source; Specimen; Speed; Stimulus; Surgeon; Synapses; Techniques; Temporal bone structure; Testing; Time; Translating; Trauma; Travel; Vestibular loss; base; bone; clinically relevant; cranium; design; experience; experimental study; hearing impairment; hearing loss risk; hearing restoration; human model; human tissue; improved; innovation; middle ear; middle ear fluid; neural stimulation; novel; otoacoustic emission; permanent hearing loss; pressure; round window; sound; spiral ganglion; tool; transmission process; vibration

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.

项目摘要/摘要 许多外科手术程序，包括旨在恢复听力的耳门学程序，涉及大量 操纵中耳和内耳的组件。特别是人工耳蜗植入物（CI） 对于某些残留声听力的患者，越来越多的表明涉及直接操纵 内耳的内容。不幸的是，这些患者中有多达约50％失去了残留的声学听力， 所有CI患者中很大一部分会立即或之后的一段时间出现平衡功能障碍 外科手术。旨在确定立即听力损失原因的几项研究表明 虽然CI电极的存在并没有实质性改变耳蜗中的声音传播 在插入过程中，在耳蜗中产生瞬态。这些相位内压力（PIC）瞬变可以 显示峰值压力超过170 dB SPL峰值等效的耳道SPL（PEAC），因此可能导致噪声 - 诱发听力或前庭丧失。这些研究是第一个确定PIC瞬变的存在，但是 无法确定来自这些暴露的来源和风险。该提议的目的是 使用两种技术克服这些先前的缺点。首先（AIM 1），我们将进一步描述PIC 尸体人类标本中CI手术期间的瞬态。 PIC测量将在 插入，操作和去除CI电极以量化产生的PIC瞬变数量，并且 与CI电极制造商，几何形状和插入样式等功能相关（即带有护套或 stylet或通过镊子）。 PIC瞬变的来源将通过子集中的实时荧光影像进行研究 这些实验将PIC事件与耳蜗中的电极位置相关联。第二（AIM 2），风险 这些PIC瞬变的听力损失将在龙猫中确定。 AIM 1中记录的PIC瞬态将是 转化为声学刺激，该刺激使用最近的龙猫中产生相同的斑点内暴露 在龙猫和人类的内耳传播之间的量化关系。这 技术，将产生与PIC相同的PIC中产生PIC的声刺激 在CI手术期间观察到的人耳蜗需要使用最近的两项创新：1）表征 关系，以及2）开发能够产生必要高级声学的扬声器 刺激。此后的实验遵循标准的噪声曝光方案，其中采用了生理措施 在噪音暴露后的几个时间点进行评估以评估动物听证会的评估 永久听力损失。因此，这些测量将提供听力损失的定量估计值 预计会暴露于CI手术期间产生的PIC瞬变，这可能会导致电极改善 设计和外科技术。该建议将开发和验证用于评估的动物模型 人噪声引起的听力损失风险。此外，由于可以为任何来源测量PIC 刺激内耳，该提案开发了一种可用于评估噪声引起的听力的技术 非传统（非空气导电）噪声源的损失风险。