Using a Joint-Otoacoustic Emission Profile to Detect and Monitor Endolymphatic Hydrops in Humans and to Explore Mechanisms of Pathology

使用联合耳声发射曲线检测和监测人类内淋巴积水并探索病理学机制

• 批准号: 10506771
• 负责人: Samantha Marie Stiepan
• 金额: $ 11.98万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506771
• 关键词: Affect; Amplifiers; Apical; Auditory; Basilar Membrane; Binaural; Clinic; Clinical; Cochlea; Cochlear Diseases; Cochlear duct; Computer Models; Counseling; Data; Detection; Diagnosis; Disease; Disease Progression; Ear; Ear Diseases; Early identification; Edema; Endolymph; Endolymphatic Hydrops; External auditory canal; Frequencies; Functional disorder; Generations; Hearing; Human; Individual; Joints; Lead; Link; Liquid substance; Maps; Measurement; Measures; Mechanics; Membrane; Meniere' s Disease; Methods; Modeling; Monitor; Morphology; Motion; Nature; Outer Hair Cells; Pathology; Patients; Phase; Physiological; Process; Production; Sensorineural Hearing Loss; Sensory; Site; Stimulus; Symptoms; Testing; TimeLine; Transducers; Travel; Vestibular Diseases; Work; absorption; base; clinical diagnosis; diagnostic biomarker; diagnostic value; hearing impairment; improved; indexing; otoacoustic emission; phenomenological models; predictive modeling; prevent; response; sound; theories; tool; transmission process

PROJECT SUMMARY/ABSTRACT Endolymphatic hydrops (EH), a hallmark of Ménière’s Disease, is a cochlear disease caused by either an over- production or under absorption of endolymphatic fluid. As a result of this excess of endolymph, the membranes bounding the endolymphatic space are distended outwards. These notable alterations in cochlear morphology cause disruptions in cochlear mechanics. The early identification and monitoring of EH is critical to preventing progression of this, oftentimes, debilitating auditory/vestibular disease (which is episodic in nature). Clinical diagnosis of EH is primarily made via symptomology, with the most reliable diagnostic marker being a fluctuating, low-frequency sensory hearing loss. EH typically progresses to sensory deficits that no longer recover, resulting in permanent hearing impairment that can eventually span across the audible frequency range. Therefore, early identification and monitoring of the disease process is critical to preventing its progression. Otoacoustic emissions (OAEs) are an ideal monitoring tool. OAEs are low-level sounds measured in the ear canal that have been shown to gauge cochlear function and dysfunction with high accuracy. Along with recent advances in this objective, efficient, and noninvasive probe of cochlear function, OAEs have the potential to be a powerful tool in improving the efficacy of EH diagnosis, given the human cochlea cannot be accessed or manipulated for direct study. We can now measure two distinct classes of emissions jointly — OAEs arising from nonlinear distortion (distortion product OAEs) and OAEs arising from coherent linear reflections (stimulus- frequency OAEs) using rapidly sweeping tones. The purpose of this work is to assess the diagnostic utility of such a Joint-OAE Profile in identifying and monitoring EH while also exploring the mechanism of disease through perceptual tests and phenomenological modeling to improve the efficacy of EH diagnosis in humans. This K01 proposal will first probe cochlear changes during EH using a Joint-OAE profile – a profile comprised of the two classes of emissions measured and analyzed together to access both generation processes (Aim 1). Additionally, we will explore the underlying mechanisms of EH by determining whether EH causes shifts in the cochlear frequency-place map using both a perceptual task (binaural pitch matching between the healthy and diseased ear within an individual) and physiological measurements of SFOAE latency (or group delay) (Aim 2). Finally, data collected from Aim 1 and 2 will be directly compared to model predictions that explore the mechanical effects of EH on the cochlear partition and the consequences for OAE generation (Aim 3). Combined, this physiological, perceptual, and computational approach to understanding endolymphatic hydrops is a comprehensive and bold attempt to understand its clinical manifestations and disease timeline, as well as its underlying mechanisms of pathology.

项目概要/摘要 内淋巴积水 (EH) 是梅尼埃病的一个标志，是一种由过度的耳蜗疾病引起的耳蜗疾病。 内淋巴液的产生或吸收不足由于内淋巴液的过量，膜。 内淋巴空间的边界向外遥远。 导致耳蜗力学紊乱 早期识别和监测 EH 对于预防至关重要。 这种疾病的进展通常会导致听力/前庭疾病（本质上是间歇性的）。 EH 的诊断主要通过症状学进行，最可靠的诊断标志物是波动的、 EH 通常会发展为无法恢复的感觉缺陷。 永久性听力损伤最终可能跨越可听频率范围，因此，尽早进行。 识别和监测疾病过程对于预防其进展至关重要。 耳声发射 (OAE) 是一种理想的监测工具，OAE 是在耳朵中测量的低电平声音。 耳蜗已被证明可以高精度地测量耳蜗功能和功能障碍。 随着这种客观、高效、无创的耳蜗功能探测技术的进步，OAE 有可能成为 鉴于人类耳蜗无法进入或无法进入，这是提高 EH 诊断效率的有力工具 我们现在可以联合测量两类不同的排放——由以下因素产生的 OAE。 非线性失真（失真产物 OAE）和相干线性反射（刺激- 频率 OAE）使用快速扫描音调这项工作的目的是评估诊断效用。 这种联合 OAE 概况可用于识别和监测 EH，同时还通过以下方式探索疾病机制： 感知测试和现象学建模，以提高人类 EH 诊断的效率。 该 K01 提案将首先使用联合 OAE 轮廓来探测 EH 期间的耳蜗变化，该轮廓包括 一起测量和分析两类排放，以了解两种发电过程（目标 1）。 此外，我们将通过确定 EH 是否导致 EH 的变化来探索 EH 的潜在机制。 使用感知任务（健康人和健康人之间的双耳音调匹配）的耳蜗频率位置图 个体患病耳朵）和 SFOAE 潜伏期（或群延迟）的生理测量（目标 2）。 最后，从目标 1 和目标 2 收集的数据将直接与探索以下问题的模型预测进行比较： EH 对耳蜗分区的机械效应以及 OAE 产生的后果（目标 3）。 结合起来，这种生理学、感知和计算方法来理解内淋巴积水 是了解其临床表现、发病时间线以及发病机制的一次全面而大胆的尝试 其潜在的病理机制。