Cochlear synaptopathy and audiometric measures from human temporal-bone cases of sensorineural hearing loss

人类感音神经性听力损失颞骨病例的耳蜗突触病和听力测量

• 批准号: 10641760
• 负责人: M. Charles Liberman
• 金额: $ 57.52万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-02 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641760
• 关键词: Acceleration; Acoustic Nerve; Acquired Deafness; Age; Aminoglycosides; Animal Model; Antibiotics; Archives; Atrophic; Audiology; Auditory Threshold; Autopsy; Axon; Big Data; Biopsy; Case Study; Cells; Cisplatin; Clinical; Clinical Trials; Cochlea; Cochlear Implants; Collection; Complex; Data; Databases; Derivation procedure; Diagnosis; Ear; Etiology; Evaluation; Eye; Formulation; Foundations; Generations; Grant; Hair Cells; Hearing Tests; Histologic; Human; Hyperacusis; Image; Inner Hair Cells; K ATPase; Labyrinth; Left; Literature; Location; Machine Learning; Measures; Meniere' s Disease; Microscopic; Modeling; Nerve Degeneration; Nerve Fibers; Nerve Regeneration; Neurons; Pathology; Patients; Pattern; Peripheral; Platinum; Presbycusis; Prevalence; Publishing; Recording of previous events; Records; Resolution; Retrospective Studies; Risk Factors; Role; Sampling; Sensorineural Hearing Loss; Sensory; Specimen; Speech; Speech Discrimination; Speed; Statistical Models; Stimulus; Subjects Selections; Synapses; Temporal bone structure; Testing; Therapeutic; Tinnitus; Toxic effect; Typology; Work; age related; animal data; cell injury; cell type; chemotherapy; clinical imaging; cochlear synaptopathy; data acquisition; deafness; ganglion cell; hearing impairment; inclusion criteria; insight; neural; noise exposure; normal aging; novel; ototoxicity; public health relevance; rat Pres protein; repaired; sex; spiral ganglion; tissue resource

Project 2 Summary - Abstract Since the inner ear cannot be biopsied, and clinical imaging cannot produce cellular-level resolution, the only way to uncover the functionally important structural changes underlying sensorineural hearing loss is the microscopic examination of post-mortem human temporal bones. This P50 Center focuses on primary neural degeneration in the inner ear (i.e. the loss of synaptic connections between surviving sensory cells and auditory nerve cells), and its hypothesized role in limiting the ability to understand complex stimuli like speech and as a key elicitor of tinnitus and hyperacusis. Over the past 5 years, Project 2 showed, as predicted from animal models, that the rate of auditory nerve loss in normal-aging human ears out-paced the rate of hair cell loss by 2:1, and that this neural loss was further accelerated in those with a history of noise exposure. A rigorous statistical model showed that while the audiometric thresholds were well predicted by the patterns of hair cell loss, the neural loss did not affect threshold but contributed to the differences in word identification abilities among those with similar audiograms. Over the next 5 years, Project 2 builds on this foundation to explore a wider range of acquired hearing loss etiologies, i.e. ototoxic antibiotics and chemotherapeutics, sudden sensorineural hearing loss and Ménière’s disease. We choose this because they are common, well represented in our temporal bone archives, and are often associated with tinnitus and difficulties in speech discrimination. We are developing machine-learning approaches to automate the acquisition of quantitative histopathological data, because we aim to grow the number of cases analyzed as rapidly as possible. As we have now entered the era of clinical trials for deafness therapeutics, there is a critical need for robust statistical models to accurately predict the degree and pattern of cellular loss from the audiogram, word score, hearing loss etiology, age and sex of a candidate patient.

项目2摘要 - 摘要 由于内耳不能进行活检，临床成像不能产生细胞级别 解决方案，揭示功能上重要的结构变化的唯一方法 感官听力损失是验尸后人类临时的显微镜检查 骨头。该P50中心的重点是内耳中的主要中性变性（即丧失 生存感官细胞和听觉神经细胞之间的突触连接）及其 假设的角色在限制理解语音等复杂刺激的能力和作为关键的能力中 耳鸣和超源刺激的诱因。 在过去的5年中，项目2从动物模型中预测到， 正常人耳朵的听觉神经损失超过2：1的毛细胞损失率，而 在暴露噪声病史的人中，这种神经损失进一步加速了。严格 统计模型表明，虽然听力阈值得到了很好的预测 毛细胞损失的模式，神经元丧失不会影响阈值，但有助于 具有相似听力图的人的单词识别能力差异。 在接下来的5年中，项目2建立在该基金会的基础上，以探索更广泛的范围 获得的听力损失病因，即耳毒性抗生素和化学治疗药突然 感官听力损失和梅尼尔氏病。我们之所以选择，是因为它们很普遍， 在我们的临时骨档案中很好地代表，通常与耳鸣和 语音歧视难度。我们正在开发机器学习方法 自动掌握定量组织病理学数据，因为我们旨在增长 尽可能快地分析的病例数。随着我们现在进入临床时代 对死亡治疗的试验，迫切需要鲁棒的统计模型准确 预测听力图，单词评分，听力损失的细胞丢失程度和模式 候选患者的病因，年龄和性别。