Visualizing the 3D cytoarchitecture of the human cochlea in an intact temporal bone using synchrotron radiation phase contrast imaging.

The gold standard method for visualizing the pathologies underlying human sensorineural hearing loss has remained post-mortem histology for over 125 years, despite awareness that histological preparation induces severe artifacts in biological tissue. Historically, the transition from post-mortem assessment to non-invasive clinical biomedical imaging in living humans has revolutionized diagnosis and treatment of disease; however, innovation in non-invasive techniques for cellular-level intracochlear imaging in humans has been difficult due to the cochlea's small size, complex 3D configuration, fragility, and deep encasement within bone. Here we investigate the ability of synchrotron radiation-facilitated X-ray absorption and phase contrast imaging to enable visualization of sensory cells and nerve fibers in the cochlea's sensory epithelium in 3D intact, non-decalcified, unstained human temporal bones. Our findings show that this imaging technique resolves the bone-encased sensory epithelium's cytoarchitecture with unprecedented levels of cellular detail for an intact, unstained specimen, and is capable of distinguishing between healthy and damaged epithelium. All analyses were performed using commercially available software that quickly reconstructs and facilitates 3D manipulation of massive data sets. Results suggest that synchrotron radiation phase contrast imaging has the future potential to replace histology as a gold standard for evaluating intracochlear structural integrity in human specimens, and motivate further optimization for translation to the clinic.