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（由适用提供）：耳蜗的功能是将复杂的声压波传输到电信号中。 Corti振动器官基于被动机械结构和基于OHC的活动过程之间的复杂相互作用。尽管激光多普勒振动已大大增加了我们对耳蜗生理学的理解，但该技术受到限制。只能测量从基底膜上的一个点开始的运动，这仅提供对实际负责听力感的替代度量：IHC立体纤毛束的挠度。这就是这些测量值无法解释Corti器官中的细胞和组织如何协同起作用以发展耳蜗扩增。需要对Corti完整器官内所有结构的振动测量来了解此过程。我们已经开发了一种新型的技术，即体积光学相干断层扫描振动仪（VOCTV，发音为“ Voctive”），该技术可以克服这些局限性，因为它可以直接通过小鼠氧胶囊骨头进行图像，并在每个体素中简单地解决病毒。这是我们了解耳蜗驱动IHC刺激的主动和被动机制，即大脑接收的输入。我们的初步数据表明，Corti器官内的频率依赖性差分运动存在。我们假设这些运动是机械地与OHC-驱动器细胞连接的倾斜度耦合的，倾斜度范围内HC的被动刚度，并且通过OHC电动性增强了倾斜度。该假设很重要，因为，如果是真的，则意味着OHC电动性不会通过增加Corti器官的垂直位移而改善听力，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。我们的研究将通过比较野生型小鼠的体内振动模式（正常的OHC刚度，正常电动性），Prestin 499小鼠（正常OHC刚度，无电静电性）和prestin null MICE（降低OHC刚度，无电动性）来明确测量OHC的作用。目的1是使用我们现有的1D-VOCTV系统来研究以两个不同角度位置的小鼠，以测量整个Corti器官的垂直和径向位移。 AIM 2是开发光学技术和软件，以对每个体素（3D-VOCTV）执行同时进行3D振动测量。 AIM 3在活小鼠中使用3D-VOCTV来测量横向，径向和纵向运动。如果我们的假设是真实的，那么与死去的野生型，活prestin 499和活prestin无小鼠相比，野生型小鼠将表现出明显的OHC-偏见细胞连接的大量径向和/或纵向位移。此外，与普雷斯汀499只小鼠相比，普雷斯汀空小鼠的这些位移的频率调整应较差。用这笔赠款获得的数据可能会解释独特且结构高度的解剖结构的基础 细胞内的细胞。该赠款开发的最先进技术可能会成为制造体内振动测量结果的新标准。