Diagnosing outer hair cell health along the cochlear partition

诊断耳蜗分区外毛细胞的健康状况

• 批准号: 7980804
• 负责人: MARK E CHERTOFF
• 金额: $ 18.8万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7980804
• 关键词: Acoustic Nerve; Action Potentials; Analysis of Variance; Anatomic Sites; Anatomic structures; Anatomy; Animal Model; Animals; Apical; Auditory; Auditory Brainstem Responses; Basilar Membrane; Behavioral; Boxing; Cells; Chinchilla (genus); Clinic; Clinical Trials; Cochlea; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Electrodes; Elements; Engineering; Equation; Etiology; Europe; External auditory canal; Fetal Tissue Transplantation; Frequencies; Future; Genetic; Gentamicins; Goals; Graph; Gray unit of radiation dose; Growth; Hair Cells; Health; Hearing; Histology; Human; Inner Hair Cells; Intervention; Labyrinth; Length; Lesion; Localized Lesion; Location; Manuscripts; Masks; Measurement; Measures; Medical; Movement; Nerve Fibers; Noise; Noise-Induced Hearing Loss; Operative Surgical Procedures; Outcome; Outer Hair Cells; Patients; Phase; Physicians; Physiological; Physiology; Population; Positioning Attribute; Probability; Procedures; Promontory; Rehabilitation therapy; Relative (related person); Reporting; Research; Review Literature; Sensorineural Hearing Loss; Shapes; Signal Transduction; Solid; Stimulus; Stria Vascularis; Structure; Sum; Techniques; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Time; TimeLine; Tissue Transplantation; Transducers; Translating; Tympanic membrane; United States; Width; base; cell injury; clinical practice; density; hair cell regeneration; hearing impairment; improved; indexing; notch protein; novel diagnostics; public health relevance; receptor; research study; response; round window; statistics; success; tool; treatment strategy; voltage

DESCRIPTION (provided by applicant): Sensorineural hearing loss results from damage to a variety of structures within the cochlea and auditory nerve. Presently, genetic and tissue transplantation strategies are being explored as therapeutic strategies for curing hearing loss. Unfortunately there are no available diagnostic techniques that isolate and distinguish the anatomic site(s) of damage within the cochlea or auditory nerve. A test battery that identifies the locus of lesion(s) will allow physicians to target the appropriate anatomic sites for medical intervention. The long-term goal of this research is to develop these diagnostic tests. In this proposal, the aim of the R21 phase is to determine if the cochlear microphonic (CM), in response to a low-frequency tone embedded in high-pass noise, can be used to quantify the location of missing outer hair cells along the cochlear partition. A cumulative distribution function (CDF) of outer hair cells is obtained by plotting the amplitude of the masked CM relative to the unmasked amplitude for specific masker frequencies. We hypothesize that the location of a plateau in the CDF (or some other variable in the CDF or corresponding probability density function) will relate to the location of missing outer hair cells. This is tested by correlating the location of missing outer hair cells estimated by the CDF with anatomic measurements in animals with hair cell lesions. In clinic populations, outer hair cells may be present but functioning abnormally. In the R33 phase we develop indices from hair cell transducer functions to determine the health of surviving outer hair cells. We hypothesize that 1) transducer function indices can be obtained along the length of the cochlea and 2) the indices can quantify outer hair cell health despite damage to other cochlear structures. The first goal is tested by correlating the location of the plateau of the CDF of an index with the location of maximum hearing loss in animals with temporary hearing loss at various frequencies. The second hypothesis is examined by comparing indices among groups of animals with lesions to outer hair cells and other structures. The studies in this proposal are likely to be translated to human patients. Presently, the CM is recorded in Audiologic clinics in the United States and Europe. Future studies optimizing stimuli and recording location are envisioned as the next step for developing diagnostic tests that compliment the new medical treatment strategies that are being explored to cure sensorineural hearing loss. PUBLIC HEALTH RELEVANCE: Hearing loss is caused by damage to a variety of anatomic structures both within the inner ear and auditory nerve. Presently, there is both a scientific and medical movement towards curing hearing loss with genetic and/or tissue transplantation techniques. Unfortunately there are no diagnostic techniques that can identify the location and health of the structures underlying hearing loss in a particular patient. The goal of this research is to develop diagnostic tests that identify the locus of lesion so that physicians can direct new medical treatments to the appropriate target.

描述（由申请人提供）： 感官听力损失导致耳蜗和听觉神经内各种结构的损害。目前，正在探索遗传和组织移植策略作为治疗听力损失的治疗策略。不幸的是，没有可用的诊断技术可以隔离和区分耳蜗或听觉神经内部损害的解剖部位。识别病变基因座的测试电池将使医生可以针对适当的解剖部位进行医疗干预。这项研究的长期目标是开发这些诊断测试。在此提案中，R21阶段的目的是确定对嵌入高通噪声的低频音调的响应，可以使用人工耳蜗微载体（CM）来量化沿耳蜗分区的缺失外毛细胞的位置。外毛细胞的累积分布函数（CDF）是通过绘制蒙版CM相对于特定掩膜频率的未掩盖振幅的振幅而获得的。我们假设高原在CDF中的位置（或CDF中的某些其他变量或相应的概率密度函数）将与缺失的外毛细胞的位置有关。通过将CDF估计的缺失外毛细胞的位置与毛细胞病变的动物的解剖测量相关联。在临床种群中，外毛细胞可能存在，但异常起作用。在R33阶段，我们从毛细胞传感器功能中开发指数，以确定存活的外毛细胞的健康。我们假设1）可以沿耳蜗的长度获得换能器功能指数，而2）尽管对其他耳蜗结构损害，但指数仍可以量化外毛细胞健康。第一个目标是通过将指数CDF高原的位置与动物在各种频率下暂时听力损失的最大听力损失的位置进行测试。通过比较具有病变的动物组与外毛细胞和其他结构的动物组之间的指标来检验第二个假设。 该提案中的研究可能会转化为人类患者。目前，CM记录在美国和欧洲的听力诊所。将未来的研究优化刺激和记录位置作为开发诊断测试的下一步，以补充正在探索的新医疗治疗策略以治愈感官性听力损失。 公共卫生相关性： 听力损失是由于内耳和听觉神经内部各种解剖结构的损害而造成的。目前，通过遗传和/或组织移植技术可以治愈听力丧失的科学和医学运动。不幸的是，没有诊断技术可以识别特定患者听力损失的结构的位置和健康。这项研究的目的是开发识别病变基因座的诊断测试，以便医生可以将新的医疗治疗引导到适当的靶标。