Browsing by Subject "Cochlea"

Now showing 1 - 9 of 9
  • Thumbnail Image
    Item
    Cochlear Implantation in US Military Veterans: A Single Institution Study
    (Sage, 2023-05-12) Totten, Douglas J.; Saltagi, Abdul; Libich, Karen; Pisoni, David B.; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objective: Military veterans have high rates of noise-induced hearing loss (NIHL) which is associated with more significant spiral ganglion neuronal loss. This study explores the relationship between NIHL and cochlear implant (CI) outcomes in veterans. Study design: Retrospective case series of veterans who underwent CI between 2019 and 2021. Setting: Veterans Health Administration hospital. Methods: AzBio Sentence Test, Consonant-Nucleus-Consonant (CNC) scores, and Speech, Spatial, and Qualities of Hearing Scale (SSQ) were measured pre- and postoperatively. Linear regression assessed relationships between outcomes and noise exposure history, etiology of hearing loss, duration of hearing loss, and Self-Administered Gerocognitive Exam (SAGE) scores. Results: Fifty-two male veterans were implanted at an average (standard deviation) age of 75.0 (9.2) years without major complications. The average duration of hearing loss was 36.0 (18.4) years. The average time of hearing aid use was 21.2 (15.4) years. Noise exposure was reported in 51.3% of patients. Objectively, AzBio and CNC scores 6 months postoperatively showed significant improvement of 48% and 39%, respectively. Subjectively, average 6-month SSQ scores showed significant improvement by 34 points (p < .0001). Younger age, SAGE score ≥17, and shorter duration of amplification were associated with higher postoperative AzBio scores. Greater improvement in AzBio and CNC scores was associated with lower preoperative scores. Noise exposure was not associated with any difference in CI performance. Conclusion: Despite high levels of noise exposure and advanced age, veterans derive substantial benefits from cochlear implantation. SAGE score ≥17 may be predictive of overall CI outcomes. Noise exposure does not impact CI outcomes.
  • Thumbnail Image
    Item
  • Thumbnail Image
    Item
    Generating high-fidelity cochlear organoids from human pluripotent stem cells
    (Elsevier, 2023) Moore, Stephen T.; Nakamura, Takashi; Nie, Jing; Solivais, Alexander J.; Aristizábal-Ramírez, Isabel; Ueda, Yoshitomo; Manikandan, Mayakannan; Reddy, V. Shweta; Romano, Daniel R.; Hoffman, John R.; Perrin, Benjamin J.; Nelson, Rick F.; Frolenkov, Gregory I.; Chuva de Sousa Lopes, Susana M.; Hashino, Eri; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ.
  • Thumbnail Image
    Item
    Human cochlear diffusion from the cerebrospinal fluid space with gadolinium contrast
    (Elsevier, 2023) Totten, Douglas J.; Booth, Kevin T. A.; Mosier, Kristine M.; Cumpston, Evan C.; Whitted, Cody; Okechuku, Vanessa; Koontz, Nicholas A.; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of Medicine
  • Thumbnail Image
    Item
    Large-scale annotated dataset for cochlear hair cell detection and classification
    (Springer Nature, 2024-04-23) Buswinka, Christopher J.; Rosenberg, David B.; Simikyan, Rubina G.; Osgood, Richard T.; Fernandez, Katharine; Nitta, Hidetomi; Hayashi, Yushi; Liberman, Leslie W.; Nguyen, Emily; Yildiz, Erdem; Kim, Jinkyung; Jarysta, Amandine; Renauld, Justine; Wesson, Ella; Wang, Haobing; Thapa, Punam; Bordiga, Pierrick; McMurtry, Noah; Llamas, Juan; Kitcher, Siân R.; López-Porras, Ana I.; Cui, Runjia; Behnammanesh, Ghazaleh; Bird, Jonathan E.; Ballesteros, Angela; Vélez-Ortega, A. Catalina; Edge, Albert S. B.; Deans, Michael R.; Gnedeva, Ksenia; Shrestha, Brikha R.; Manor, Uri; Zhao, Bo; Ricci, Anthony J.; Tarchini, Basile; Basch, Martín L.; Stepanyan, Ruben; Landegger, Lukas D.; Rutherford, Mark A.; Liberman, M. Charles; Walters, Bradley J.; Kros, Corné J.; Richardson, Guy P.; Cunningham, Lisa L.; Indzhykulian, Artur A.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.
  • Thumbnail Image
    Item
    Large-scale annotated dataset for cochlear hair cell detection and classification
    (bioRxiv, 2023-09-01) Buswinka, Christopher J.; Rosenberg, David B.; Simikyan, Rubina G.; Osgood, Richard T.; Fernandez, Katharine; Nitta, Hidetomi; Hayashi, Yushi; Liberman, Leslie W.; Nguyen, Emily; Yildiz, Erdem; Kim, Jinkyung; Jarysta, Amandine; Renauld, Justine; Wesson, Ella; Thapa, Punam; Bordiga, Pierrick; McMurtry, Noah; Llamas, Juan; Kitcher, Siân R.; López-Porras, Ana I.; Cui, Runjia; Behnammanesh, Ghazaleh; Bird, Jonathan E.; Ballesteros, Angela; Vélez-Ortega, A. Catalina; Edge, Albert S. B.; Deans, Michael R.; Gnedeva, Ksenia; Shrestha, Brikha R.; Manor, Uri; Zhao, Bo; Ricci, Anthony J.; Tarchini, Basile; Basch, Martin; Stepanyan, Ruben S.; Landegger, Lukas D.; Rutherford, Mark; Liberman, M. Charles; Walters, Bradley J.; Kros, Corné J.; Richardson, Guy P.; Cunningham, Lisa L.; Indzhykulian, Artur A.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Our sense of hearing is mediated by cochlear hair cells, localized within the sensory epithelium called the organ of Corti. There are two types of hair cells in the cochlea, which are organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains a few thousands of hair cells, and their survival is essential for our perception of sound because they are terminally differentiated and do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. However, the sheer number of cells along the cochlea makes manual quantification impractical. Machine learning can be used to overcome this challenge by automating the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, human, pig and guinea pig cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 90'000 hair cells, all of which have been manually identified and annotated as one of two cell types: inner hair cells and outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to supply other groups within the hearing research community with the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.
  • Thumbnail Image
    Item
    Multimodal Atlas of the Murine Inner Ear: From Embryo to Adult
    (Frontiers Media, 2021-07-15) Bryant, Jean-Paul; Chandrashekhar, Vikram; Cappadona, Anthony J.; Lookian, Pashayar P.; Chandrashekhar, Vibhu; Donahue, Danielle R.; Munasinghe, Jeeva B.; Kim, H. Jeffrey; Vortmeyer, Alexander O.; Heiss, John D.; Zhuang, Zhengping; Rosenblum, Jared S.; Pathology and Laboratory Medicine, School of Medicine
    The inner ear is a complex organ housed within the petrous bone of the skull. Its intimate relationship with the brain enables the transmission of auditory and vestibular signals via cranial nerves. Development of this structure from neural crest begins in utero and continues into early adulthood. However, the anatomy of the murine inner ear has only been well-characterized from early embryogenesis to post-natal day 6. Inner ear and skull base development continue into the post-natal period in mice and early adulthood in humans. Traditional methods used to evaluate the inner ear in animal models, such as histologic sectioning or paint-fill and corrosion, cannot visualize this complex anatomy in situ. Further, as the petrous bone ossifies in the postnatal period, these traditional techniques become increasingly difficult. Advances in modern imaging, including high resolution Micro-CT and MRI, now allow for 3D visualization of the in situ anatomy of organs such as the inner ear. Here, we present a longitudinal atlas of the murine inner ear using high resolution ex vivo Micro-CT and MRI.
  • Thumbnail Image
    Item
    The role of ADF and cofilin in auditory sensory cell development
    (2020-12) McGrath, Jamis; Perrin, Benjamin; Cummins, Theodore; Belecky-Adams, Teri; Balakrishnan, Lata; Zhao, Bo
    Our ability to hear relies on sensory cells found in the inner ear that transduce sound into biological signals. Microvilli-like protrusions called stereocilia are bundled on the apical surfaces of these cells and allow them to respond to sound-evoked vibrations. The architecture of the stereocilia bundle is highly patterned to ensure normal hearing. Filaments of polymerized actin proteins are bundled in parallel into large cylindrical structures that define the dimensions of stereocilia. This network is then anchored to the cell by inserting into another actin-based structure called the cuticular plate, which forms a gel-like structure and facilitates the mechanical properties of the bundle. The shape of the bundle is determined through tissue-level and intrinsic polarization signaling pathways. Auditory brainstem-evoked response testing, immunofluorescence imaging, scanning electron microscopy, and biochemical labeling techniques were used to study how the ADF/cofilin family of actin filament severing and depolymerizing proteins contributes to the development of the stereocilia bundle. Loss of these proteins disrupts the normal bundle patterning process, changes the lengths and widths of stereocilia, and alters the regulation of filament ends near the ion channel at stereocilia tips that is responsible for mechanotransduction. The activity of this channel regulates ADF/cofilins and the actin at stereocilia tips. Aberrant actin growth in actin networks beneath the stereocilia bundle influences the bundle patterning process, causes dysmorphic bundles to form. This work identifies that ADF/cofilins are necessary during auditory sensory cell development to facilitate normal bundle patterning and establishes this protein family as a molecular link between mechanotransduction and stereocilia bundle maturation.
  • Thumbnail Image
    Item
    Selection of viral capsids and promoters affects the efficacy of rescue of Tmprss3-deficient cochlea
    (Elsevier, 2023-08-11) Aaron, Ksenia A.; Pekrun, Katja; Atkinson, Patrick J.; Billings, Sara E.; Abitbol, Julia M.; Lee, Ina A.; Eltawil, Yasmin; Chen, Yuan-Siao; Dong, Wuxing; Nelson, Rick F.; Kay, Mark A.; Cheng, Alan G.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Adeno-associated virus (AAV)-mediated gene transfer has shown promise in rescuing mouse models of genetic hearing loss, but how viral capsid and promoter selection affects efficacy is poorly characterized. Here, we tested combinations of AAVs and promoters to deliver Tmprss3, mutations in which are associated with hearing loss in humans. Tmprss3tm1/tm1 mice display severe cochlear hair cell degeneration, loss of auditory brainstem responses, and delayed loss of spiral ganglion neurons. Under the ubiquitous CAG promoter and AAV-KP1 capsid, Tmprss3 overexpression caused striking cytotoxicity in vitro and in vivo and failed to rescue degeneration or dysfunction of the Tmprss3tm1/tm1 cochlea. Reducing the dosage or using AAV-DJ-CAG-Tmprss3 diminished cytotoxicity without rescue of the Tmprss3tm1/tm1 cochlea. Finally, the combination of AAV-KP1 capsid and the EF1α promoter prevented cytotoxicity and reduced hair cell degeneration, loss of spiral ganglion neurons, and improved hearing thresholds in Tmprss3tm1/tm1 mice. Together, our study illustrates toxicity of exogenous genes and factors governing rescue efficiency, and suggests that cochlear gene therapy likely requires precisely targeted transgene expression.