3-D optical imaging of the in vivo organ of Corti motion at a sub-nanometer scale

描述（由申请人提供）：低光学相干断层扫描（OCT）已被用于生物组织成像，是商业上可用于人眼晶状体和细胞结构成像的显微镜的理论基础。基于OCT的干涉仪尚未生产，但具有独特的性能，可用于内耳组织和细胞的振动测量。我们建议开发一种OCT干涉仪，该干涉仪既能成像Corti的活体器官，又能测量其细胞的三维运动，振动小至0.1 nm。OCT干涉测量的基本概念已经被证明对Corti器官的微观力学有用。该提案实现了技术进步，允许在细胞水平上确定器官位移矢量的方向和相位所需的更高分辨率。通过使用飞秒脉冲激光，该仪器将具有约3立方微米的成像和振动分辨率。这是通过结合一种新的相敏OCT方法来完成的，该方法允许仪器用于测试被膜在侧向（径向）方向上机械共振的假设。包括共振在内的被盖膜的体内力学知识，将终结四分之一世纪以来关于器官如何实现内耳毛细胞立体纤毛的有效机械刺激以及随后哺乳动物听觉的非凡灵敏度的猜想。

DESCRIPTION (provided by applicant): Low optical coherence tomography (OCT) has been used to image biological tissue and is the theoretical basis of microscopes that are commercially available to image the lens and cellular structures of the human eye. Interferometers based on OCT have not been produced but have unique properties useful for vibration measurements of the tissues and cells of the inner ear. We propose to develop an OCT interferometer that has the ability to both image the living organ of Corti and measure its cellular motion in 3-dimensions down to a vibration as small as 0.1 nm. The basic concept of OCT interferometry has already proven usefulness for the micromechanics of the organ of Corti. This proposal implements technical advances that permit needed higher resolution that enables determination of the direction and phase of the organ displacement vector at the cellular level. The instrument will have an imaging and vibration resolution of about 3 cubic micrometers through the use of a femtosecond pulsed laser. This is accomplished by incorporation of a novel phase-sensitive OCT approach allowing the instrument to be used to test the hypothesis that the tectorial membrane is mechanically resonant in the lateral (radial) direction. Knowledge of the in vivo mechanics of the tectorial membrane, including resonance, will set to rest a quarter century of conjecture on how the organ achieves the efficient mechanical stimulation of the inner ear hair cell stereocilia and the subsequent remarkable sensitivity of mammalian hearing. PUBLIC HEALTH RELEVANCE: The discoveries of cochlear mechanics that this optical coherence tomography (OCT) instrument will allow are critical to the understanding of normal hearing, the mechanisms of the otoacoustic emissions that are used as clinical audiometric tests and the defects in hearing caused by loud sound and by deafness genes. The OCT method we will develop also has other applications for human health in Otolaryngology: OCT could image the vibration of the middle ear structures as an audiometric method, measure blood flow in the human inner ear to classify which patients with sudden deafness have deficient flow or measure and map blood flow in a microvascular skin flap to improve the viability of flaps.