We strive to understand the biological mechanisms of hearing loss and then translate this knowledge to directly and rapidly improve the care of patients with hearing loss.

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Rationale

A common clinical scenario is that a child is initially identified with a partial hearing loss, which then progresses to profound hearing loss over a period of months to years. Genetic defects are responsible for over half of these cases, however the specific mechanisms of how many of these mutations cause progressive sensorineural hearing loss is unclear. Right now, all we can tell a patient with hearing loss is that we know they have hearing loss, and that it is because of a problem in the cochlea. There are no more detailed tests available.

Methodology

Because of the difficulty in performing auditory research in humans, we study normal and transgenic mice that have hearing loss. We strive to perform comprehensive evaluation of the pathophysiology that creates the hearing loss. To do this, we develop novel technology to permit in vivo imaging and physiological measurements. We have created Volumetric Optical Coherence Tomography and Vibrometry (VOCTV) to non-invasively measure the vibratory patterns of intra-cochlear tissues. The level of detail within the cochlea that we can now image is roughly two orders of magnitude better than what is currently available with the latest MRI or CT techniques. Our goal is to be able to identify why any given patient that comes to clinic has hearing loss, and use this information to guide management using regenerative strategies that are in active development.

Examples

A mouse cochlea imaged using OCT.

The traveling wave along the tectorial membrane and basilar membrane within the mouse cochlea in response to a 20 dB SPL 7 kHz tone. These measurements were collected using our VOCTV system (Lee HY, Raphael PD, Park J, Ellerbee AK, Applegate BE, Oghalai JS. Noninvasive in vivo imaging reveals differences between tectorial membrane and basilar membrane traveling waves in the mouse cochlea. Proc Natl Acad Sci. 2015 Mar 10;112(10):3128–33).

The 2-D vibratory patterns within the mouse organ of Corti. We measured this using our VOCTV system (Lee HY, Raphael PD, Xia A, Kim J, Grillet N, Applegate BE, et al. Two-Dimensional Cochlear Micromechanics Measured In Vivo Demonstrate Radial Tuning within the Mouse Organ of Corti. J Neurosci. Society for Neuroscience; 2016 Aug 3;36(31):8160–73).

We are working now to translate this technology for use in humans. We expect that when this technique becomes available, doctors will be able to better diagnose and treat diseases of the middle and inner ear.

Inner Hair Cell – Auditory Nerve

We are studying how auditory neurons can be lost with aging or noise exposure. Below are videos which show one inner hair cell and multiple auditory nerve dendrites which connect to it.

Only auditory neurons connected to the pillar side fire in response to a quiet sound.

In response to a loud sound, auditory nerves on both the pillar and modiolar side fire.

After noise trauma, modiolar side neurons are lost. In response to a quiet sound, the pillar side neurons fire in a normal fashion.

In response to a loud sound after noise trauma, less information is conveyed to the brain, because the modiolar side neurons have been lost.