Optical coherence tomography for 3D measures of cochlear mechanics in vivo

用于体内耳蜗力学 3D 测量的光学相干断层扫描

• 批准号: 9454168
• 负责人: John S Oghalai
• 金额: $ 41.12万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-10 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9454168
• 关键词: 3-Dimensional; Algorithms; Auditory; Basilar Membrane; Biomechanics; Brain; Cells; Cochlea; Complex; Computer software; Coupled; Data; Frequencies; Generations; Grant; Hair Cells; Hearing; Image; Individual; Intercellular Junctions; Knockout Mice; Lasers; Length; Link; Liquid substance; Mammals; Measurement; Measures; Mechanics; Motion; Mouse Strains; Movement; Mus; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Organ; Organ of Corti; Outer Hair Cells; Pattern; Peripheral; Phase; Physiology; Positioning Attribute; Preparation; Process; Radial; Research Technics; Role; Signal Transduction; Stapes; Structure; Subcellular Anatomy; Supporting Cell; System; Techniques; Technology; Testing; Time; Tissues; Transgenic Mice; Trauma; Wild Type Mouse; Work; base; bone; capsule; experimental study; imaging system; improved; in vivo; mouse model; novel; pressure; public health relevance; rat Pres protein; response; sound; vector; vibration

 DESCRIPTION (provided by applicant): The function of the cochlea is to transduce complex sound pressure waves into electrical signals. Organ of Corti vibration is based upon a complex interplay between passive mechanical structures and active OHC- based processes. While laser Doppler vibrometry has added tremendously to our understanding of cochlear physiology, this technique is limited. Only motion from one point on the basilar membrane can be measured, and this provides only a surrogate measure for what is actually responsible for the sense of hearing: deflection of the IHC stereociliary bundle. Thus, these measurements alone cannot explain how the cells and tissues within the organ of Corti work collaboratively to develop cochlear amplification. Vibratory measurements of all of the structures within the intact organ of Corti are needed to understand this process. We have developed a novel technique, volumetric optical coherence tomography vibrometry (VOCTV, pronounced "voctive") that overcomes these limitations because it can image directly through the mouse otic capsule bone and simultaneously resolve vibrations at every voxel. Thus, we are at the cusp of understanding how the active and passive mechanics of the cochlea drive IHC stimulation, i.e. the input received by the brain. Our preliminary data demonstrate that frequency-dependent differential motion within the organ of Corti exists. We hypothesize that these movements are mechanically coupled to tilting of the OHC-Deiter cell junction, that the tilting varies with the passive stiffness of the HC, and that the tilting is enhanced by OHC electromotility. This hypothesis is important because, if true, it means that OHC electromotility improves hearing not by increasing vertical displacements of the organ of Corti, but by converting vertical displacement of the basilar membrane into radial fluid movement that can stimulate IHCs. Our studies will explicitly measure the role of the OHC by comparing the in vivo vibratory patterns of wild-type mice (normal OHC stiffness, normal electromotility), prestin 499 mice (normal OHC stiffness, no electromotility), and prestin null mice (decreased OHC stiffness, no electromotility). Aim 1 is to use our existing 1D-VOCTV system to study mice positioned at two different angles to measure both vertical and radial displacements throughout the organ of Corti. Aim 2 is to develop the optical technology and software to perform simultaneous 3D vibratory measurements for every voxel (3D-VOCTV). Aim 3 is use 3D-VOCTV in living mice to measure transverse, radial, and longitudinal motion. If our hypothesis is true, wild- type mice will demonstrate significantly largr radial and/or longitudinal displacements of the OHC-Deiter cell junction compared to dead wild-type, live prestin 499, and live prestin null mice. In addition, the frequency tuning of these displacements should be less sharp in prestin null mice compared to prestin 499 mice. The data obtained with this grant will likely explain the basis for the unique and highly structured anatomy of cells within the organ of Corti. The state-of-the-art technology developed with this grant is likely to become the new standard for making in vivo vibratory measurements.

 描述（由申请人提供）：耳蜗的功能是将复杂的声压波转换为电信号。Corti器官振动是基于被动机械结构和主动OHC过程之间的复杂相互作用。虽然激光多普勒振动测量法极大地增加了我们对耳蜗生理学的理解，但这种技术是有限的。只有从基底膜上的一个点的运动可以被测量，这只提供了一个替代措施，什么是真正负责的听觉：偏转的IHC静纤毛束。因此，这些测量本身不能解释Corti器官内的细胞和组织如何协同工作以发展耳蜗放大。需要对完整的Corti器官内的所有结构进行振动测量，以了解这一过程。我们已经开发了一种新的技术，体积光学相干断层扫描振动测量（VOCTV，发音为“voctive”），克服了这些限制，因为它可以直接通过小鼠耳囊骨成像，同时解决每个体素的振动。因此，我们正处于理解耳蜗的主动和被动机制如何驱动IHC刺激的尖端，即大脑接收的输入。我们的初步数据表明，频率依赖性的差异运动内的Corti器官存在。我们假设，这些运动是机械耦合到倾斜的OHC-Deiter细胞交界处，倾斜与HC的被动刚度的变化，并通过OHC电活动性的倾斜增强。这一假设很重要，因为如果是真的，这意味着OHC电活动性不是通过增加Corti器官的垂直位移来改善听力，而是通过将基底膜的垂直位移转换为可以刺激IHC的径向流体运动。我们的研究将通过比较野生型小鼠（正常OHC刚度，正常电运动性）、普雷斯廷499小鼠（正常OHC刚度，无电运动性）和普雷斯廷缺失小鼠（OHC刚度降低，无电运动性）的体内振动模式来明确测量OHC的作用。目的1是使用我们现有的1D-VOCTV系统来研究定位在两个不同角度的小鼠，以测量整个Corti器官的垂直和径向位移。目标2是开发光学技术和软件，以执行每个体素（3D-VOCTV）的同时三维振动测量。目的3：利用三维VOCTV测量活体小鼠的横向、径向和纵向运动。如果我们的假设是正确的，则野生型小鼠与死亡的野生型、活的普雷斯廷499和活的普雷斯廷无效小鼠相比，将显示出OHC-Deiter细胞连接的显著更大的径向和/或纵向位移。此外，与普雷斯廷499小鼠相比，这些位移的频率调谐在普雷斯廷缺失小鼠中应该不那么尖锐。通过这项资助获得的数据可能会解释独特和高度结构化的解剖学的基础 Corti器官中的细胞。这项资助开发的最先进的技术很可能成为体内振动测量的新标准。