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成电信号，该功能基于被动机械结构和基于 OHC 的主动过程之间的复杂相互作用。极大地影响了我们对耳蜗生理学的理解，这种技术只能测量基底膜上一个点的运动，而这仅提供了一种替代测量方法，以了解实际负责感觉的因素。听力：IHC 立体纤毛束的偏转因此，这些测量本身无法解释柯蒂氏器官内的细胞和组织如何协同工作以产生耳蜗放大，需要对完整柯蒂氏器官内的所有结构进行振动测量。我们开发了一种新技术，即体积光学相干断层扫描振动测量（VOCTV，发音为“voctive”），它克服了这些限制，因为它可以直接通过小鼠耳囊骨成像并同时解析。因此，我们即将了解耳蜗的主动和被动机制如何驱动 IHC 刺激，即大脑接收到的输入，柯蒂氏器官内的频率相关的微分运动。我们见证了这些运动与 OHC-Deiter 细胞连接的倾斜机械耦合，倾斜随着 HC 的被动刚度而变化，并且 OHC 电动性增强了倾斜。重要的是，如果这是真的，这意味着 OHC 电动性不是通过增加柯蒂氏器的垂直位移来改善听力，而是通过将基底膜的垂直位移转化为可以刺激 IHC 的径向流体运动来改善听力。通过比较野生型小鼠（正常 OHC 硬度、正常电动性）、prestin 499 小鼠（正常 OHC 硬度、无电动性）和 prestin 的体内振动模式零小鼠（OHC 刚度降低，无电动性） 目标 1 是使用我们现有的 1D-VOCTV 系统研究处于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。技术和软件对每个体素进行同步 3D 振动测量 (3D-VOCTV) 目标 3 在活体小鼠中使用 3D-VOCTV 来测量横向、如果我们的假设成立，那么与死亡的野生型、活的 prestin 499 和活的 prestin null 小鼠相比，野生型小鼠的 OHC-Deiter 细胞连接处将表现出显着较大的径向和/或纵向位移。此外，与 prestin 499 小鼠相比，prestin null 小鼠中这些位移的频率调整应该不那么尖锐。通过这项资助获得的数据可能会解释独特且高度结构化的解剖结构的基础。 利用这笔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。