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.

项目概要/摘要 许多外科手术，包括旨在恢复听力的耳科手术，都涉及大量的手术 操纵中耳和内耳的部件。特别是人工耳蜗 (CI)， 越来越多地适用于具有一些残余声学听力的患者，涉及直接操纵 内耳的内容物。不幸的是，高达约 50% 的患者丧失了残余听觉，并且 所有 CI 患者中很大一部分立即或术后一段时间出现平衡功能障碍 外科手术。几项旨在确定立即听力损失原因的研究表明， 虽然 CI 电极的存在不会显着改变耳蜗中的声音传输，但高水平 插入期间耳蜗中会产生瞬变。这些耳蜗内压力 (PIC) 瞬变可以 显示峰值压力超过 170 dB SPL 峰值等效耳道 SPL (PEAC)，因此可能会导致噪音 诱发听力或前庭丧失。这些研究首次确定了 PIC 瞬变的存在，但是 未能确定这些暴露的来源和风险。该提案的目标是 使用两种技术克服了以前的这些缺点。首先（目标 1），我们将进一步表征 PIC 人体尸体标本 CI 手术期间的瞬变。 PIC 测量将在 插入、操作和移除 CI 电极以量化生成的 PIC 瞬变数量，以及 与 CI 电极制造商、几何形状和插入类型（即带有护套或 管心针或通过镊子）。 PIC 瞬变的来源将通过实时荧光镜成像在一个子集中进行研究 这些实验将 PIC 事件与耳蜗中的电极位置相关联。第二（目标 2），风险 这些 PIC 瞬变造成的听力损失将在龙猫中确定。目标 1 中记录的 PIC 瞬态将是 使用最近的方法转化为声刺激，在龙猫中产生相同的耳蜗内暴露 龙猫和人类内耳声音传输之间的量化关系。这 技术，该技术将产生声音刺激，使龙猫产生与 在 CI 手术期间观察到的人类耳蜗需要使用两项最新创新：1) 表征 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 在噪声暴露之前和之后的几个时间点评估动物听力，以评估所产生的结果 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 瞬变可能会导致电极的改进 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 人类噪音引起的听力损失风险。此外，由于 PIC 可以针对任何源进行测量， 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（非空气传导）噪声源的损失风险。