Human otopathology without invading the cochlea imaged using optical coherence tomography and verified with novel histological technique

Abstract The human cochlea is encapsulated and mostly embedded in bone. Within the cochlea, complex architecture of delicate microstructures function to transduce sound vibrations into neuronal signals. Difficult access and internal fragility have limited our knowledge of the natural anatomy of the human cochlea. Thus, much of our understanding of human cochlear anatomy comes from processed histology. With this proposal, we will determine the fresh natural structural anatomy of human cochleae and its functional mechanical motion in situ from unfixed and fresh cadaveric specimens with the use of Optical Coherence Tomography (OCT), which can image and measure the motion of fresh human cochlear structures in their natural state without invading the cochlea. Here, we propose a coordinated study of human cochlear anatomy and pathology based on OCT imaging and vibrometry of fresh (<30 hours postmortem) unfixed human cochleae in situ, and light microscopy imaging of histology prepared from the same donor. We will use OCT to noninvasively image and measure the motion of the cochlear partition through the round window in one ear (Aim 1). To better interpret OCT images, we will advance a novel rapid histological method to process both the OCT-imaged ear and the contralateral ear from each donor, and section them to obtain views of the same cochlear location as imaged with OCT (Aim 2). Direct OCT and histology comparisons from the same donor will enable us to better identify the extent to which OCT can visualize cochlear structures and quantify histological processing artifacts. Our work will result in better understanding of fresh human cochlear anatomy, which will set the stage for future possibilities and may have profound clinical implications. The ability to noninvasively image and identify cochlear structures may enable us to identify and diagnose pathologies in patients that previously could only be visualized with histology in postmortem tissue. Intracochlear imaging would be invaluable for the testing of new pharmaceutical therapies, as the success of these drugs may require that baseline anatomical conditions of the cochlea be met, such as the survival of supporting cells or a near-normal appearance of the organ of Corti. With the future development of endoscopic OCT probes, our results could translate quickly to the clinic and help to better identify pathology and select the therapy with the highest chance for success in patients.