Tomographic Imaging of Cochlear Micromechanical Motions

描述（由申请人提供）：耳蜗是一种卓越的传感器：活体耳蜗能够可靠地检测导致镫骨运动的皮米级的声音，能够进行高质量的频率分析（Q10 dB> 600），并将听觉的大动态范围（120 dB）压缩到神经元的相当小的动态范围（20- 50 dB）中。现在人们普遍认为，一个积极的机械放大过程的基础上这些显着的性质。然而，关于放大器的性质存在相当大的争论。虽然有关听力的细胞和分子基础的信息正在迅速增加，但对这些组成部分如何相互作用以产生听力的显着特性仍然知之甚少。 迄今为止，最成功的实验研究细胞运动在生活耳蜗使用光学方法。然而，目前的方法，如激光多普勒测振仪和视频显微镜受到耳蜗结构的低反射率和完整的耳蜗提供的有限的光学通路的限制。这项资助的目的是开发和应用一种新的断层成像和运动测量技术，能够确定活的完整耳蜗中所有结构的三维运动。光学相干断层扫描（OCT）将用于获得耳蜗的高分辨率图像。将通过与激光多普勒测振法中所用类似的狭窄开口或可能直接通过骨采集图像。在声刺激期间，将通过OCT探测器信号的同步解调生成频闪图像序列。计算机视觉算法（类似于视频显微镜方法中使用的算法）将用于确定纳米分辨率的运动。该技术将被应用于图像和测量三维运动的内部微结构的一个完整的耳蜗，包括基底膜，网状层，覆膜，和外毛细胞。

DESCRIPTION (provided by applicant): The cochlea is a remarkable sensor: a living cochlea can reliably detect sounds that cause motions of the stapes on the order of picometers, is capable of high-quality frequency analysis (Q10dB > 600), and compresses the large dynamic range (120 dB) of hearing into the considerably smaller dynamic range (20- 50 dB) of neurons. It is now widely accepted that an active mechanical amplification process underlies these remarkable properties. However, there is considerable debate about the nature of the amplifier. While information on the cellular and molecular basis of hearing is increasing rapidly, there is still little understanding of how the components interoperate to generate the remarkable properties of hearing. To date, the most successful experimental studies of cellular motions in living cochleae have used optical methods. However, current methods, such as laser Doppler vibrometry and video microscopy are limited by the low reflectivities of cochlear structures and the limited optical access provided by the intact cochea. The objective of this grant is to develop and apply a new tomographic imaging and motion measurement technique capable of determining the three-dimensional motions of all structures in a living, intact cochlea. Optical coherence tomography (OCT) will be used to obtain high-resolution images of the cochlea. Images will be acquired through a narrow opening similar to that used in laser Doppler vibrometry methods, or possibly directly through bone. Sequences of stroboscopic images will be generated with synchronous demodulation of the OCT detector signal during acoustic stimulation. Computer vision algorithms (similar to those used in video microscopy methods) will be used to determine motions with nanometer resolution. This technique will be applied to image and measure three-dimensional motions of the internal microstructure of an intact cochlea, including the basilar membrane, reticular lamina, tectorial membrane, and outer hair cells.