Growth and cellular patterning during fetal human inner ear development studied by a correlative imaging approach

Lejo Johnson Chacko, David Wertjanz, Consolato Sergi, Jozsef Dudas, Natalie Fischer, Theresa Eberharter, Romed Hoermann, Rudolf Glueckert, Helga Fritsch, Helge Rask-Andersen, Anneliese Schrott-Fischer & Stephan Handschuh - Department of Otorhinolaryngology, Medical University of Innsbruck ; Department of Laboratory Medicine & Pathology, Division of Anatomical Pathology, 5B4.09 Walter C MacKenzie Health Sciences Centre, University of Alberta ; Department of Anatomy, Histology & Embryology, Division of Clinical & Functional Anatomy, Medical University of Innsbruck ; Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Uppsala University Hospital ; VetCore Facility for Research, Imaging Unit, University of Veterinary Medicine Vienna

Progressive transformation of the otic placode into the functional inner ear during gestational development in humans leads to the acquisition of hearing perception via the cochlea and balance and spatial orientation via the vestibular organ.

Using a correlative approach involving micro-computerized tomography (micro-CT), transmission electron microscopy and histological techniques we were able to examine both the morphological and cellular changes associated with human inner ear development. Such an evaluation allowed for the examination of 3D geometry with high spatial and temporal resolution. In concert with gestational progression and growth of the cochlear duct, an increase in the distance between some of the Crista ampullaris is evident in all the specimens examined from GW12 to GW36. A parallel increase in the distances between the macular organs – fetal utricle and saccule – is also evident across the gestational stages examined. The distances between both the utricle and saccule to the three cristae ampullares also increased across the stages examined. A gradient in hair cell differentiation is apparent from apex to base of the fetal cochlea even at GW14.

We present structural information on human inner ear development across multiple levels of biological organization, including gross-morphology of the inner ear, cellular and subcellular details of hearing and vestibular organs, as well as ultrastructural details in the developing sensory epithelia. This enabled the gathering of detailed information regarding morphometric changes as well in realizing the complex developmental patterns of the human inner ear. We were able to quantify the volumetric and linear aspects of selected gestational inner ear specimens enabling a better understanding of the cellular changes across the fetal gestational timeline. Moreover, these data could serve as a reference for better understanding disorders that arise during inner ear development.

How Amira-Avizo Software is used

Reconstructed image volumes were exported in DICOM format. Scans were imported to Amira® 6.4.0, and nerves and structures of the membranous labyrinth were manually segmented switching between the three orthogonal planes using the Segmentation editor. Segmented structures such as the membranous labyrinth, perilymphatic compartments of the whole inner ear, vestibular end organs, and vestibulocochlear nerve were visualized using volume and surface renderings.