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.

项目总结/摘要 内淋巴积水（EH）是梅尼埃病的标志，是一种耳蜗疾病， 内淋巴液的产生或吸收不足。由于这种过量的内淋巴， 包围内淋巴空间的神经细胞向外扩张。这些耳蜗形态的显著改变 导致耳蜗力学的中断。早期发现和监测高血压是预防高血压的关键 这种通常使人衰弱的听觉/前庭疾病的进展（其本质上是偶发性的）。临床 EH的诊断主要是通过病理学进行的，最可靠的诊断标志物是波动的， 低频感觉性听力损失EH通常进展为不再恢复的感觉缺陷， 永久性听力障碍，最终可以跨越可听频率范围。因此早期 确定和监测疾病进程对防止其发展至关重要。 耳声发射（OAE）是一种理想的监测工具。耳声发射是在耳中测量的低水平声音 已经显示出能够以高精度测量耳蜗功能和功能障碍。沿着最近 随着这种客观、有效和无创的耳蜗功能探头的发展，耳声发射有可能成为 一个强大的工具，在提高EH诊断的有效性，鉴于人类耳蜗无法访问或 进行直接研究。我们现在可以联合测量两种不同类别的排放-OAE产生于 非线性失真（失真产物OAE）和由相干线性反射（刺激- 频率OAE）。这项工作的目的是评估诊断效用的 这种联合OAE特征在识别和监测EH中的作用，同时还通过以下方式探索疾病的机制： 知觉测试和现象学建模，以提高人类EH诊断的功效。 该K 01提案将首先使用关节OAE配置文件探测EH期间的耳蜗变化-该配置文件包括 这两类排放量一起测量和分析，以访问两个生成过程（目标1）。 此外，我们还将通过确定高血压是否导致高血压患者的脑组织中 耳蜗频率-位置图，其使用感知任务（健康人和 个体内的患病耳）和SFOAE潜伏期（或群延迟）的生理测量（目的2）。 最后，从目标1和目标2收集的数据将直接与模型预测进行比较， EH对耳蜗分区的机械效应和OAE产生的后果（目的3）。 结合，这种生理，感知和计算的方法来了解内淋巴积水 是一个全面和大胆的尝试，以了解其临床表现和疾病的时间轴，以及 其潜在的病理机制。