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Background: Despite its location near infection-prone areas, the human inner ear demonstrates remarkable resilience. This suggests that there are inherent instruments deterring the invasion and spread of pathogens into the inner ear. Here, we combined high-resolution light microscopy, super-resolution immunohistochemistry (SR-SIM) and synchrotron phase contrast imaging (SR-PCI) to identify the protection and barrier systems in the various parts of the human inner ear, focusing on the lateral wall, spiral ganglion, and endolymphatic sac. Materials and methods: Light microscopy was conducted on mid-modiolar, semi-thin sections, after direct glutaraldehyde/osmium tetroxide fixation. The tonotopic locations were estimated using SR-PCI and 3D reconstruction in cadaveric specimens. The sections were analyzed for leucocyte and macrophage activity, and the results were correlated with immunohistochemistry using confocal microscopy and SR-SIM. Results: Light microscopy revealed unprecedented preservation of cell anatomy and several macrophage-like cells that were localized in the cochlea. Immunohistochemistry demonstrated IBA1 cells frequently co-expressing MHC II in the spiral ganglion, nerve fibers, lateral wall, spiral limbus, and tympanic covering layer at all cochlear turns as well as in the endolymphatic sac. RNAscope assays revealed extensive expression of fractalkine gene transcripts in type I spiral ganglion cells. CD4 and CD8 cells occasionally surrounded blood vessels in the modiolus and lateral wall. TMEM119 and P2Y12 were not expressed, indicating that the cells labeled with IBA1 were not microglia. The round window niche, compact basilar membrane, and secondary spiral lamina may form protective shields in the cochlear base. Discussion: The results suggest that the human cochlea is surveilled by dwelling and circulating immune cells. Resident and blood-borne macrophages may initiate protective immune responses via chemokine signaling in the lateral wall, spiral

Objective: Cochlear implants are traditionally programmed to stimulate according to a generalized frequency map, where individual anatomic variability is not considered when selecting the centre frequency of stimulation of each implant electrode. However, high variability in cochlear size and spatial frequency distributions exist among individuals. Generalized cochlear implant frequency maps can result in large pitch perception errors and reduced hearing outcomes for cochlear implant recipients. The objective of this work was to develop an individualized frequency mapping technique for the human cochlea to allow for patient-specific cochlear implant stimulation. Methods: Ten cadaveric human cochleae were scanned using synchrotron radiation phase-contrast imaging (SR-PCI) combined with computed tomography (CT). For each cochlea, ground truth angle-frequency measurements were obtained in three-dimensions using the SR-PCI CT data. Using an approach designed to minimize perceptual error in frequency estimation, an individualized frequency function was determined to relate angular depth to frequency within the cochlea. Results: The individualized frequency mapping function significantly reduced pitch errors in comparison to the current gold standard generalized approach. Conclusion and Significance: This paper presents for the first time a cochlear frequency map which can be individualized using only the angular length of cochleae. This approach can be applied in the clinical setting and has the potential to revolutionize cochlear implant programming for patients worldwide.

Objectives: Prussak's space (PS) is an intricate middle ear region which may play an essential role in the development of middle ear disease. The three-dimensional (3D) anatomy of the human PS and its drainage routes remain relatively unknown. Earlier studies have histologically analyzed PS, by micro-dissection and endoscopy. Here, we used synchrotron-radiation phase-contrast imaging (SR-PCI), 3D reconstructions, and modeling to study the framework of the human PS, including aeration pathways. It may lead to increased understanding of development of middle ear pathology. Design: Nine human temporal bone specimens underwent in-line SR-PCI at the Canadian Light Source in Saskatoon, Saskatchewan, Canada. Data were processed with volume-rendering software to create 3D reconstructions using scalar opacity mapping and segmentations to visualize its walls in fixed, undecalcified human temporal bones. Results: The PS was found to be an irregular, variably shaped chamber with different aeration systems. Three different drainage pathways were found: 1) via the posterior malleolar pouch of von Troltsch in seven of nine ears; 2) directly posterior-inferior into the mesotympanum medial to the posterior malleolar pouch in one ear; and 3) anteriorly in another. The posterior-inferior communications depended on the anatomy of the posterior malleolar fold. In one bilateral case, the aeration differed between the ears. Earlier descriptions of upper ventilation routes between the PS and the epitympanic spaces could not be substantiated. Conclusions: The 3D anatomy of the membrane folds organizing the PS in humans was demonstrated for the first time using in-line SR-PCI. The PS was always aerated into the mesotympanum, suggesting its relative independence of attic ventilation. The impact of its various drainage routes on middle ear ventilation and disease were discussed.

Hypothesis: Measuring the length of the basilar membrane (BM) in the cochlear hook region will result in improved accuracy of cochlear duct length (CDL) measurements. Background: Cochlear implant pitch mapping is generally performed in a patient independent approach, which has been shown to result in place-pitch mismatches. In order to customize cochlear implant pitch maps, accurate CDL measurements must be obtained. CDL measurements generally begin at the center of the round window (RW) and ignore the basal-most portion of the BM in the hook region. Measuring the size and morphology of the BM in the hook region can improve CDL measurements and our understanding of cochlear tonotopy. Methods: Ten cadaveric human cochleae underwent synchrotron radiation phase-contrast imaging. The length of the BM through the hook region and CDL were measured. Two different CDL measurements were obtained for each sample, with starting points at the center of the RW (CDLRW) and the basal-most tip of the BM (CDLHR). Regression analysis was performed to relate CDLRW to CDLHR. A three-dimensional polynomial model was determined to describe the average BM hook region morphology. Results: The mean CDLRW value was 33.03 ± 1.62 mm, and the mean CDLHR value was 34.68 ± 1.72 mm. The following relationship was determined between CDLRW and CDLHR: CDLHR = 1.06(CDLRW)-0.26 (R2 = 0.99). Conclusion: The length and morphology of the hook region was determined. Current measurements underestimate CDL in the hook region and can be corrected using the results herein.

Background: The etiology of Meniere's disease (MD) and endolymphatic hydrops believed to underlie its symptoms remain unknown. One reason may be the exceptional complexity of the human inner ear, its vulnerability, and surrounding hard bone. The vestibular organ contains an endolymphatic duct system (EDS) bridging the different fluid reservoirs. It may be essential for monitoring hydraulic equilibrium, and a dysregulation may result in distension of the fluid spaces or endolymphatic hydrops. Material and Methods: We studied the EDS using high-resolution synchrotron phase contrast non-invasive imaging (SR-PCI), and micro-computed tomography (micro-CT). Ten fresh human temporal bones underwent SR-PCI. One bone underwent micro-CT after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue resolution. Data were processed using volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and tissue segmentation. Results: Combined imaging techniques with segmentation and tissue modeling demonstrated the 3D anatomy of the human saccule, utricle, endolymphatic duct, and sac together with connecting pathways. The utricular duct (UD) and utriculo-endolymphatic valve (UEV or Bast's valve) were demonstrated three-dimensionally for the first time. The reunion duct was displayed with micro-CT. It may serve as a safety valve to maintain cochlear endolymph homeostasis under certain conditions. Discussion: The thin reunion duct seems to play a minor role in the exchange of endolymph between the cochlea and vestibule under normal conditions. The saccule wall appears highly flexible, which may explain occult hydrops occasionally preceding symptoms in MD on magnetic resonance imaging (MRI). The design of the UEV and connecting ducts suggests that there is a reciprocal exchange of fluid among the utricle, semicircular canals, and the EDS. Based on the anatomic framework and previous experimental data, we speculate that precipito

Background: Reports vary on the incidence of vestibular dysfunction and dizziness in patients following cochlear implantation (CI). Disequilibrium may be caused by surgery at the cochlear base, leading to functional disturbances of the vestibular receptors and endolymphatic duct system (EDS) which are located nearby. Here, we analyzed the three-dimensional (3D) anatomy of this region, aiming to optimize surgical approaches to limit damage to the vestibular organ. Material and Methods: A total of 22 fresh-frozen human temporal bones underwent synchrotron radiation phase-contrast imaging (SR-PCI). One temporal bone underwent micro-computed tomography (micro-CT) after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue contrast. We used volume-rendering software to create 3D reconstructions and tissue segmentation that allowed precise assessment of anatomical relationships and topography. Macerated human ears belonging to the Uppsala collection were also used. Drilling and insertion of CI electrodes was performed with metric analyses of different trajectories. Results and Conclusions: SR-PCI and micro-CT imaging demonstrated the complex 3D anatomy of the basal region of the human cochlea, vestibular apparatus, and EDS. Drilling of a cochleostomy may disturb vestibular organ function by injuring the endolymphatic space and disrupting fluid barriers. The saccule is at particular risk due to its proximity to the surgical area and may explain immediate and long-term post-operative vertigo. Round window insertion may be less traumatic to the inner ear, however it may affect the vestibular receptors.

Meniere’s disease remains enigmatic, and has no treatment with sufficient evidence. The characteristic histopathological finding is endolymphatic hydrops, suggesting either an overproduction or decreased reabsorption of endolymph in the human inner ear. This study presents the first analysis of the vascular plexus around the human endolymphatic duct using micro computed tomography and coherent synchrotron radiation with phase contrast imaging. Using a software program, data were processed by volume-rendering with scalar opacity mapping to create transparent three-dimensional reconstructions. A rich vascular plexus was discovered around the endolymphatic duct that drained into collecting channels, linked to the vestibular venous outflow system. This network is believed to make up the principal route for endolymph outflow, and its associated malfunction may result in endolymphatic hydrops and Meniere’s disease., De tre sista författarna delar sistaförfattarskapet