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，包括旨在恢复听力的耳科手术，都涉及大量的 推拿中耳和内耳的部件。尤其是人工耳蜗术(CI)，它是 对于有一些残留听力的患者，越来越多的适应症包括直接操作 内耳的内容物。不幸的是，这些患者中高达50%的人失去了残余的听力，并且 相当大比例的CI患者在即刻或一段时间后出现平衡功能障碍 做手术。几项旨在确定即刻听力损失原因的研究表明 虽然CI电极的存在不会实质上改变耳蜗中的声音传输，但高水平的 在插入过程中，耳蜗会产生瞬变。这些脑室内压(PIC)瞬变可以 显示峰值压力超过170分贝SPL峰值等效耳道SPL(PEAC)，因此可能会引起噪音- 诱发性听力丧失或前庭丧失。这些研究首次确定了PIC瞬变的存在，但 未能确定这些暴露的来源和听证的风险。这项提议的目标是 使用两种技术克服这些先前的缺点。首先(目标1)，我们将进一步描述PIC 脑梗塞手术中身体标本的瞬变。将在以下时间进行PIC测量 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、几何形状和插入样式(即带护套或 针头或通过钳子)。将在子集中使用实时荧光成像来研究PIC瞬变的来源 这些实验的结果是将PIC事件与耳蜗内电极位置相关联。第二个(目标2)，风险 这些PIC瞬变导致的听力损失将在龙猫身上确定。目标1中记录的PIC瞬变将是 转化为声学刺激，在栗鼠身上产生相同的耳廓内暴露 龙猫和人类内耳中声音传播的量化关系。这 技术，它将产生声音刺激，在龙猫身上产生与 在CI手术中观察到的人类耳蜗，需要使用两个最新的创新：1)表征 关系，以及2)能够产生所需的高电平声学的扬声器的开发 刺激物。此后的实验遵循标准的噪声暴露方案，在该方案中生理测量 对动物的听力在暴露前和暴露后的几个时间点进行评估，以评估由此产生的 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。 预计暴露于CI手术期间产生的PIC瞬变可能导致电极改善 设计和外科技术。该提案将由此开发并验证用于评估的动物模型 人类噪声导致听力损失的风险。此外，由于PIC可以针对满足以下条件的任何源进行测量 刺激内耳，这项建议开发了一种技术，可以用来评估噪音诱导的听力 非传统(非空气传导)噪声源的损失风险。