DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

HRRP-funded investigators develop miniature imaging probe to visualize cellular pathology in the inner ear

Posted December 1, 2021

Janani S. Iyer1, Biwei Yin2, Konstantina M. Stankovic1,3 and Guillermo J. Tearney2

1Massachusetts Eye and Ear and Harvard Medical School
2Massachusetts General Hospital
3Stanford University School of Medicine

Konstantina M. Stankovic, M.D., Ph.D.
Konstantina M. Stankovic,
M.D., Ph.D.

Hearing loss affects nearly 15% of American adults. Damage to cells or cellular structures in the inner ear is a leading cause of hearing loss. Coiled into a few millimeters in diameter and encased in hard bones, the inner ear is difficult to access and examine, creating a tremendous hurdle for matching potential therapeutics to the correct patients and evaluating therapeutic effects. In a recent Scientific Reports publication, co-authors Dr. Janani Iyer and Dr. Biwei Yin, under the supervision of Dr. Konstantina Stankovic and Dr. Guillermo Tearney, made significant advancements in addressing this critical gap. With funding from a FY19 Hearing Restoration Research Program Focused Research Award, they have developed a sub-millimeter-diameter, flexible endomicroscopic probe to image cellular structures in the inner ear at micron-scale resolution.

Guillermo J. Tearney, M.D., Ph.D.


Guillermo J. Tearney,
M.D., Ph.D.

A patient’s type of hearing loss depends on whether hearing impairment occurs in the outer, middle and/or inner ear. Normally, the outer ear captures and funnels sound waves into the middle ear which conducts the vibrations along to the inner ear. Therefore, impairment of sound wave conduction within the outer and middle ear is called conductive hearing loss (1). The inner ear, which includes the cochlea and cochlear branch of the auditory nerve, is where the mechanical inputs of sound waves are converted to electrical signals. Central to this process are auditory hair cells in the organ of Corti, a spiral organ located inside the cochlea. Outer hair cells amplify the sound wave; sensory inner hair cells change the mechanical wave into a neural signal that is transmitted by the cochlear nerve to the auditory processing centers of the brain (1). Therefore hearing loss from damage to the inner ear is called sensorineural hearing loss (SNHL). SNHL accounts for the majority of hearing impairment (1), including noise-induced hearing loss and age-related hearing loss. While SNHL affects tens of millions of Americans and hundreds of millions worldwide, there is no FDA-approved drug to treat SNHL nor method to examine the cellular pathologies in SNHL patients. Currently, clinicians use computed tomography (CT) and/or magnetic resonance imaging (MRI) to assess inner ear pathology. A CT scan is often a low-yield study for examining the inner ear; it involves exposure to radiation and does not directly depict the cochlear nerve, only the bone that contains it (2,3). A MRI of the inner ear can visualize nerve bundles and is recommended to evaluate pathology of the pathway between the cochlea and brain but resolution is inferior to CT (2,3). Neither imaging method can visualize the inner ear on the cellular-level needed for an objective diagnosis of the pathological cause of a patient’s SNHL.

To address these issues, Dr. Stankovic and team developed and tested a micro-optical coherence tomography (µOCT) catheter. µOCT is a minimally invasive imaging technique that generates two- and three-dimensional images by measuring properties of the back-scattered or back-reflected light from different depths within a biological tissue. The team has previously tested a 1-µm resolution µOCT system on dissected mouse organs of Corti, demonstrating the µOCT could visualize individual cells and nerve fibers and distinguish between healthy and noise-damaged tissue. In the new publication, they take on the challenge of imaging the organ of Corti inside the inner ear’s bone casing. This was achieved by interfacing the µOCT system with a specially designed sub-millimeter-diameter, flexible optic probe. Inserting the probe through the membrane separating the middle and inner ear, the team collected intracochlear, endoscopic µOCT images of the organ of Corti in human cadaveric cochlea, which revealed structural details of diagnostic relevance for SNHL pathology. The images are the first of its kinds and represent a breakthrough in intraocular endoscopy technology.

The miniature intracochlear µOCT catheter holds great promise for in vivo examination of inner ear pathology, a missing yet crucial piece in the puzzle of SNHL therapeutic development and clinical trials. Its potential clinical applications also include real-time guidance of cochlear implantation, thus improving the positioning of implant electrode arrays and hearing outcomes in implant patients.

Publication:

Iyer, J.S., Yin, B., Stankovic, K.M. et al. Endomicroscopy of the human cochlea using a micro-optical coherence tomography catheter. Sci Rep 11, 17932 (2021). https://doi.org/10.1038/s41598-021-95991-8

References:

1. Tanna RJ, Lin JW, De Jesus O. Sensorineural Hearing Loss. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK565860/

2. Prince ADP, Stucken EZ. Sudden Sensorineural Hearing Loss: A Diagnostic and Therapeutic Emergency. The Journal of the American Board of Family Medicine Jan 2021, 34 (1) 216-223; DOI: 10.3122/jabfm.2021.01.200199

3. Young JY, Ryan ME, Young NM. Preoperative imaging of sensorineural hearing loss in pediatric candidates for cochlear implantation. Radiographics. 2014 Sep-Oct;34(5):E133-49. doi: 10.1148/rg.345130083. PMID: 25208295.

Link:

Public and Technical Abstract: Miniature Intracochlear Imaging Probe Based on Micro-Optical Coherence Tomography for Cellular-Level Diagnosis and Therapy of Hearing Loss

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Last updated Monday, January 3, 2022