Osteogenesis Imperfecta: Implications of Using Micro-CT for Visualizing Developmental Variation in the Middle and Inner Ear of OIM Mice

Osteogenesis Imperfecta: Implications of Using Micro-CT for Visualizing Developmental Variation in the Middle and Inner Ear of OIM Mice Dallin R. Judd1, Brenton R. Stucki1, Courtney A. Miller2, Emma Handler3, Rachel A. Menegaz2, Lauren A. Gonzales2 1 Texas College of Osteopathic Medicine, University of North Texas Health Science Center, TX 2 Department of Physiology and Anatomy, University of North Texas Health Science Center, TX 3 Department of Anatomy and Cell Biology, University of Iowa, IA Osteogenesis imperfecta (OI), also known as brittle bone disease, is a genetic bone disorder caused by mutations in the genes COL1A1 and COL1A2, which are responsible for encoding type I collagen. Much is known regarding the effects of the disease on cranial and postcranial elements. However, little is known regarding the pathogenesis and physical manifestations of OI in the ear despite the high rates of hearing loss in patients with OI (~60% of the population is affected). Because ossification or demineralization of structures in the ear may affect the efficacy of certain treatments like cochlear implants, this information deficit limits the treatment options available for OI patients. Thus, the purpose of our research is to visualize and document anatomic variation in the ears of mice bred to have the Type III OI genetic variant in order to better understand the cause of OI-related hearing loss. 3D models of the middle and inner ears were created from micro-CT scans that also employed two new contrast-enhanced methods to visualize the cochlea and middle ear (malleus, incus, and stapes). All CT scanning were done on the UNTHSC campus using the new Small Animal Imaging Facility (SAIF) as part of a previous study. The scan resolution was approximately 20μm. The studied WT and OIM mouse samples include three time points intended to capture a developmental sequence: 0-day-old (WT=20, OIM=29), 7-day-old (WT=23, OIM=23), and 14-day-old mice (WT=22, OIM=18). The visualization software Avizo was then used to digitally segment the bone of the inner ear and middle ear. Gross anatomic differences are currently being documented for each region. Previous work has shown higher levels of ossification and marked bony encroachment of the otic capsule onto the cochlea in the adult OIM mouse model, potentially damaging the soft tissue of the membranous labyrinth. This research uses micro-CT imaging designed to capture a developmental sequence, giving us the potential to elucidate how and when the bony intrusions are impacting surrounding structures. Insight into this anatomical damage may help further clarify OI-related pathology, including the distinction between hearing loss associated with the middle ear (conductive hearing loss) vs. hearing loss associated with the inner ear (sensorineural hearing loss). Furthermore, a preliminary analysis of the developmental sequence should provide insight into when these anatomical changes are first occurring. Upon completion, this research will demonstrate the efficacy of using these new imaging approaches for studying minute structures of the ear and may markedly advance our understanding of the pathogenesis of OI-related hearing loss.