Integrating histology and translational imaging of the human cochlea

The National Institute on Deafness and Other Communication Disorders awarded Massachusetts Eye and Ear Infirmary $692,124 on July 15, 2026, under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) to integrate histology and translational imaging of the human cochlea.

The award funds development and validation of optical coherence tomography (OCT) imaging to visualize internal cochlear structures noninvasively through the intact round window in fresh human cadaveric specimens. The research couples OCT imaging with a novel rapid histological processing method using Technovit that reduces processing time to two months compared with over a year using traditional celloidin techniques and produces less structural distortion. By comparing histological cross-sections and OCT images from the same cochlear location in the same specimen, the research team will improve interpretation of OCT images for anatomical microstructure characterization. The project addresses two specific aims: understanding natural cochlear structure and developing clinical diagnostic capability for cochlear pathologies to guide safe therapeutic delivery, particularly for gene therapies.

Performance takes place in Boston, Massachusetts. The period of performance runs from July 15, 2026, through May 31, 2031. Massachusetts Eye and Ear Infirmary, a Harvard Medical School-affiliated nonprofit research institution, is the award recipient. The assistance type is a Project Grant.

Abstract

Our understanding of human cochlear anatomy and physiology in vivo has been limited by our inability to visualize the internal structures of the cochlea without disrupting IT. To study human cochlear anatomy, scientists have mostly relied on century-old celloidin histological processes that are both very slow and distort cochlear structures. This inability to noninvasively look within the living cochlea also has major clinical implications. Current clinical tests can only provide indirect evidence of cochlear pathologies. With recent successes in genetic therapies, advances in cochlear imaging are important to enable micro-structural anatomical diagnosis for therapy selection and to facilitate safer delivery of intracochlear therapies. With optical coherence tomography (OCT), DR. Nakajima's team has imaged the cochlear partition in very fresh human cadaveric specimens in situ in their natural state through the intact round window, without entering the cochlea. This shows great promise for non-invasive in vivo imaging and its use for both diagnosis and for guiding therapeutic delivery. However, OCT images require further development because of their granularity. This proposed research addresses challenges in using OCT to (1) understand natural cochlear structure; and (2) clinically diagnose cochlear pathologies and help guide safe therapeutic delivery. In aim 1, we couple OCT in fresh human cadaveric specimens with a novel rapid histological method to process the same OCT-imaged ears. This groundbreaking histologic technique with technovit, developed by DR. Eckhard, is less distorting and requires only 2 months to process (rather than over a year with celloidin). By comparing the histological correlate and OCT image of the same cross-sectional location in the same cochlea, we can better interpret non-invasive OCT images of anatomical micro-structures in the fresh cochlea. This provides a roadmap to use OCT to diagnose human cochlear pathology from its anatomy in vivo. In aim 2, we will develop, build, and test an OCT endoscope for low-risk in vivo imaging in patients. DR. Applegate will lead the redesign of his OCT endoscope, integrating features from his previous generation with insights gained through human cadaveric head and temporal bone testing in collaboration with DR. Cheng, who is experienced in OCT imaging and otologic endoscopic surgery. They will develop and test our OCT endoscope devices and techniques for non-invasive imaging using contemporary surgical approaches and design considerations of anatomical constraints. By leveraging our multidisciplinary expertise and our unique resources, we will develop imaging approaches for the cochlea and obtain the first in vivo images of the cochlear partition in living patients. This work will be critical for enabling point of care OCT imaging diagnoses to precisely target treatments in patients and to more safely guide the delivery of those treatments.