Cochlear morphology and cochlear duct length (CDL) play important roles in the selection of appropriate electrodes. Cochlear parameters such as diameter (A value) and width (B value) are used as inputs for calculating the CDL. Current measurements of these parameters are inefficient and time consuming. Recently developed otological planning software (OTOPLAN) allows surgeons to directly measure these parameters and then automatically calculate the CDL.

We have developed a technique to deliver cells to the inner ear without injuring the membranes that seal the endolymphatic and perilymphatic chambers. The integrity of these membranes is essential for normal hearing, and the technique should significantly reduce surgical trauma during cell transplantation. Embryonic stem cells transplanted at the internal auditory meatal portion of an atrophic auditory nerve migrated extensively along it. Four-five weeks after transplantation, the cells were found not only throughout the auditory nerve, but also in Rosenthal's canal and the scala media, the most distal portion of the auditory nervous system where the hair cells reside. Migration of the transplanted cells was more extensive following damage to the auditory nerve. In the undamaged nerve, migration was more limited, but the cells showed more signs of neuronal differentiation. This highlights an important balance between tissue damage and the potential for repair.

Estimating insertion depth, cochlear duct length (CDL), and other inner ear parameters is vital to optimizing cochlear implantation outcomes. Most current formulas use only the basal turn dimensions for CDL prediction. In this study, we investigated the importance of the second turn parameters in estimating CDL. Two experienced neuro-otologists blindly used segmentation software to measure (in mm) cochlear parameters, including basal turn diameter (A), basal turn width (B), second-turn diameter (A2), second-turn width (B2), CDL, first-turn length, and second-turn length (STL). These readings were taken from 33 computed tomography (CT) images of temporal bones from anatomically normal ears. We constructed regression models using A, B, A2, and B2 values fitted to CDL, two-turn length, and five-fold cross-validation to ensure model validity. CDL, A value, and STL were longer in males than in females. The mean B2/A2 ratio was 0.91 ± 0.06. Adding A2 and B2 values improved CDL prediction accuracy to 86.11%. Therefore, we propose a new formula for more accurate CDL estimation using A, B, A2, and B2 values. In conclusion, the findings of this study revealed a notable improvement in the prediction of two-turn length (2TL), and CDL by clinically appreciable margins upon adding A2 and B2 values to the prediction formulas.

In the field of cochlear implantation, the current trend toward patient-specific electrode selection and the achievement of optimal audiologic outcomes has resulted in implant manufacturers developing a large portfolio of electrodes. The aim of this study was to bridge the gap between the known variability of cochlea length and this electrode portfolio.

The avian cochlear duct houses both a vestibular and auditory sensory organ (the lagena macula and basilar papilla, respectively), which each have a distinct structure and function. Comparative mRNA in situ hybridization mapping conducted over the time course of chicken cochlear duct development reveals that Wnt-related gene expression is concomitant with various developmental processes such as regionalization, convergent extension of the cochlear duct, cell fate specification, synaptogenesis, and the establishment of planar cell polarity. Wnts mostly originate from nonsensory tissue domains, whereas the sensory primordia preferentially transcribe Frizzled receptors, suggesting that paracrine Wnt signaling predominates in the cochlear duct. Superimposed over this is the strong expression of two secreted Frizzled-related Wnt inhibitors that tend to show complementary expression patterns. Frzb (SFRP3) is confined to the nonsensory cochlear duct and the lagena macula, whereas SFRP2 is maintained in the basilar papilla along with Fzd10 and Wnt7b. Flanking the basilar papilla are Wnt7a, Wnt9a, Wnt11, and SFRP2 on the neural side and Wnt5a, Wnt5b, and Wnt7a on the abneural side. The lateral nonsensory cochlear duct continuously expresses Frzb and temporarily expresses Wnt6 and SFRP1. Characteristic for the entire lagena is the expression of Frzb; in the lagena macula are Fzd1, Fzd7, and Wnt7b, and in the nonsensory tissues are Wnt4 and Wnt5a. Auditory hair cells preferentially express Fzd2 and Fzd9, whereas the main receptors expressed in vestibular hair cells are Fzd1 and Fzd7, in addition to Fzd2 and Fzd9.

Introduction  Successful cochlear implantation requires an appropriate insertion depth of the electrode, which depends on cochlear duct length CDL). The CDL can vary due to ethnic factors. Objective  The objective of the current study was to determine the CDL in an Indian adult cadaveric population. Methods  The present was a cadaveric study using the temporal bones obtained after permission of the Institutional Review Board. The temporal bones were subjected to high-resolution computed tomography (HRCT), and the double oblique reformatted CT images were reconstructed through the basal turn of the cochlea. The reformatted images were then viewed in the minimum-intensity projection (minIP) mode, and the 'A' value (the diameter of the basal turn of the cochlea) was calculated. The CDL was then measured using the formula CDL = 4.16A - 4 (Alexiades et al). The data analysis was performed using the Microsoft Excel software, version 2016. Results  A total of 51 temporal bones were included for imaging analysis. The CDL varied from 27.6 mm to 33.4 mm, with a mean length of 30.7 mm. There was no statistically significant difference between the two sides. Conclusion  The CDL can be calculated with preoperative high-resolution CT, and can provide a roadmap for effective cochlear implant electrode insertion. The population-based anatomical variability needs to be taken into account to offer the most efficient and least traumatic insertion of the electrode.

Age-related hearing loss is a progressive sensorineural hearing loss that occurs during aging. Degeneration of the organ of Corti and atrophy of the lateral wall of the cochlear duct (or scala media) in the inner ear are the two primary causes. MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA/protein targets, are important regulators of cellular senescence and aging. We examined miRNA gene expression profiles in the lateral wall of two mouse strains, along with exploration of the potential targets of those miRNAs that showed dynamic expression during aging. We show that 95 and 60 miRNAs exhibited differential expression in C57 and CBA mice during aging, respectively. A majority of downregulated miRNAs are known to regulate pathways of cell proliferation and differentiation, while all upregulated miRNAs are known regulators in the pro-apoptotic pathways. By using apoptosis-related gene array and bioinformatic approaches to predict miRNA targets, we identify candidate miRNA-regulated genes that regulate apoptosis pathways in the lateral wall of C57 and CBA mice during aging.

Despite significant anatomical variation amongst patients, cochlear implant frequency-mapping has traditionally followed a patient-independent approach. Basilar membrane (BM) length is required for patient-specific frequency-mapping, however cochlear duct length (CDL) measurements generally extend to the apical tip of the entire cochlea or have no clearly defined end-point. By characterizing the length between the end of the BM and the apical tip of the entire cochlea (helicotrema length), current CDL models can be corrected to obtain the appropriate BM length. Synchrotron radiation phase-contrast imaging has made this analysis possible due to the soft-tissue contrast through the entire cochlear apex.

Knowledge about cochlear duct length (CDL) may assist electrode choice in cochlear implantation (CI). However, no gold standard for clinical applicable estimation of CDL exists. The aim of this study is (1) to determine the most reliable radiological imaging method and imaging processing software for measuring CDL from clinical routine imaging and (2) to accurately predict the insertion depth of the CI electrode.

A notable example of spiral architecture in organs is the mammalian cochlear duct, where the morphology is critical for hearing function. Genetic studies have revealed necessary signaling molecules, but it remains unclear how cellular dynamics generate elongating, bending, and coiling of the cochlear duct. Here, we show that extracellular signal-regulated kinase (ERK) activation waves control collective cell migration during the murine cochlear duct development using deep tissue live-cell imaging, Förster resonance energy transfer (FRET)-based quantitation, and mathematical modeling. Long-term FRET imaging reveals that helical ERK activation propagates from the apex duct tip concomitant with the reverse multicellular flow on the lateral side of the developing cochlear duct, resulting in advection-based duct elongation. Moreover, model simulations, together with experiments, explain that the oscillatory wave trains of ERK activity and the cell flow are generated by mechanochemical feedback. Our findings propose a regulatory mechanism to coordinate the multicellular behaviors underlying the duct elongation during development.

Growing interest in measuring the cochlear duct length (CDL) has emerged, since it can influence the selection of cochlear implant electrodes. Currently the measurements are performed with ionized radiation imaging. Only a few studies have explored CDL measurements in magnetic resonance imaging (MRI). Therefore, the presented study aims to fill this gap by estimating CDL in MRI and comparing it with multislice computed tomography (CT).

Cochlear size and morphology vary greatly and may influence the course of a cochlear implant electrode array during insertion and its final intra-cochlear position. Detailed insight into these variations is valuable for characterizing each cochlea and offers the opportunity to study possible correlations with surgical or speech perception outcomes. This study presents an automatic tracing method to assess individual cochlear duct shapes from clinical CT images. On pre-operative CT scans of 479 inner ears the cochlear walls were discriminated by interpolating voxel intensities along radial and perpendicular lines within multiplanar reconstructions at 1 degree intervals from the round window. In all 479 cochleas, the outer wall could be traced automatically up to 720 degrees. The inner wall and floor of the scala tympani in 192 cochleas. The shape of the cochlear walls were modelled using a logarithmic spiral function including an offset value. The vertical trajectories of the scala tympani exhibited a non-monotonous spiral slope with specific regions at risk for CI-related insertion trauma, and three slope categories could be distinguished. This presented automatic tracing method allows the detailed description of cochlear morphology and can be used for both individual and large cohort evaluation of cochlear implant patients.

The development of the capillary network in the stria vascularis and in the underlying spiral ligament of gerbils was systematically and quantitatively investigated by conventional electron microscopy and confocal laser microscopy in association with vascular labeling with fluorescent gelatin. The developmental changes of capillaries in the lateral wall were observed as the following series of events. (i) At 0 days after birth (DAB) capillaries already existed in the spiral ligament as a network. (ii) At 3-9 DAB the capillary network developed into two layers starting from the scala vestibuli side to the scala tympani side; one layer was located in the stria and the other in the spiral ligament. (iii) At 9 DAB capillaries in the stria became separated from the spiral ligament, and the capillary network consisting of a two-layered structure was complete. (iv) Total capillary length and capillary density in the lateral wall increased until 9 DAB and leveled off thereafter, but changes in the relative position of capillaries in the stria toward the luminal surface of marginal cells continued until 31 DAB. On the basis of the above observations, we propose two possible mechanisms underlying the vascular development in the lateral wall: (i) the formation of new vasculature (angiogenesis), and (ii) changes in the position of cellular components relative to capillaries in association with the differentiation and maturation of marginal cells and intermediate cells.

The A-value used in cochlear duct length (CDL) estimation does not take malformed cochleae into consideration. The objective was to determine the A-value reported in the literature, to assess the accuracy of the A-value measurement and to evaluate a novel cochlear measurement in distinguishing malformed cochlea. High resolution Computer Tomography images in the oblique coronal plane/cochlear view of 74 human temporal bones were analyzed. The A-value and novel C-value measurement were evaluated as predictors of inner ear malformation type. The proximity of the facial nerve to the basal turn was evaluated subjectively. 26 publications report on the A-value; but they do not distinguish normal vs. malformed cochleae. The A-values of the normal cochleae compared to the cochleae with cochlear hypoplasia, incomplete partition (IP) type I, -type II, and -type III were significantly different. The A-value does not predict the C-value. The C-values of the normal cochleae compared to the cochleae with IP type I and IP type III were significantly different. The proximity of the facial nerve to the basal turn did not relate to the type of malformation. The A-value is different in normal vs. malformed cochleae. The novel C-value could be used to predict malformed anatomy, although it does not distinguish all malformation types.

Neonatal mouse cochlear duct cells can proliferate and grow in vitro into inner ear organoids. Distinctive cochlear duct cell types have different organoid formation capacities. Here, we provide a flow cytometric cell-sorting method that allows the subsequent culture of individual cochlear cell populations. For the efficient culture of the sorted cells, we provide protocols for growing free-floating inner ear organoids, the adherence of organoids to a substrate, and the expansion of organoid-derived inner ear colonies. For complete details on the use and execution of this protocol, please refer to Kubota et al. (2021).

Hair cells of the developing mammalian inner ear are progressively defined through cell fate restriction. This process culminates in the expression of the bHLH transcription factor Atoh1, which is necessary for differentiation of hair cells, but not for their specification. Loss of several genes will disrupt ear morphogenesis or arrest of neurosensory epithelia development. We previously showed in null mutants that the loss of the transcription factor, Gata3, results specifically in the loss of all cochlear neurosensory development. Temporal expression of Gata3 is broad from the otic placode stage through the postnatal ear. It therefore remains unclear at which stage in development Gata3 exerts its effect. To better understand the stage specific effects of Gata3, we investigated the role of Gata3 in cochlear neurosensory specification and differentiation utilizing a LoxP targeted Gata3 line and two Cre lines. Foxg1(Cre)∶Gata3(f/f) mice show recombination of Gata3 around E8.5 but continue to develop a cochlear duct without differentiated hair cells and spiral ganglion neurons. qRT-PCR data show that Atoh1 was down-regulated but not absent in the duct whereas other hair cell specific genes such as Pou4f3 were completely absent. In addition, while Sox2 levels were lower in the Foxg1(Cre):Gata3(f/f) cochlea, Eya1 levels remained normal. We conclude that Eya1 is unable to fully upregulate Atoh1 or Pou4f3, and drive differentiation of hair cells without Gata3. Pax2-Cre∶Gata3(f/f) mice show a delayed recombination of Gata3 in the ear relative to Foxg1(Cre):Gata3(f/f) . These mice exhibited a cochlear duct containing patches of partially differentiated hair cells and developed only few and incorrectly projecting spiral ganglion neurons. Our conditional deletion studies reveal a major role of Gata3 in the signaling of prosensory genes and in the differentiation of cochlear neurosenory cells. We suggest that Gata3 may act in combination with Eya1, Six1, and Sox2 in cochlear prosensory gene signaling.

Here we describe the bony anatomy of the inner ear and surrounding structures seen in three plesiomorphic crown mammalian petrosal specimens. Our study sample includes the triconodont Priacodon fruitaensis from the Upper Jurassic of North America, and two isolated stem therian petrosal specimens colloquially known as the Höövör petrosals, recovered from Aptian-Albian sediments in Mongolia. The second Höövör petrosal is here described at length for the first time. All three of these petrosals and a comparative sample of extant mammalian taxa have been imaged using micro-CT, allowing for detailed anatomical descriptions of the osteological correlates of functionally significant neurovascular features, especially along the abneural wall of the cochlear canal. The high resolution imaging provided here clarifies several hypotheses regarding the mosaic evolution of features of the cochlear endocast in early mammals. In particular, these images demonstrate that the membranous cochlear duct adhered to the bony cochlear canal abneurally to a secondary bony lamina before the appearance of an opposing primary bony lamina or tractus foraminosus. Additionally, while corroborating the general trend of reduction of venous sinuses and plexuses within the pars cochlearis seen in crownward mammaliaforms generally, the Höövör petrosals show the localized enlargement of a portion of the intrapetrosal venous plexus. This new vascular feature is here interpreted as the bony accommodation for the vein of cochlear aqueduct, a structure that is solely, or predominantly, responsible for the venous drainage of the cochlear apparatus in extant therians. Given that our fossil stem therian inner ear specimens appear to have very limited high-frequency capabilities, the development of these modern vascular features of the cochlear endocast suggest that neither the initiation or enlargement of the stria vascularis (a unique mammalian organ) was originally associated with the capacity for high-frequency hearing or precise sound-source localization.

In mammals, sound is detected by mechanosensory hair cells that are activated in response to vibrations at frequency-dependent positions along the cochlear duct. We demonstrate that inner ear supporting cells provide a structural framework for transmitting sound energy through the cochlear partition. Humans and mice with mutations in GAS2, encoding a cytoskeletal regulatory protein, exhibit hearing loss due to disorganization and destabilization of microtubule bundles in pillar and Deiters' cells, two types of inner ear supporting cells with unique cytoskeletal specializations. Failure to maintain microtubule bundle integrity reduced supporting cell stiffness, which in turn altered cochlear micromechanics in Gas2 mutants. Vibratory responses to sound were measured in cochleae from live mice, revealing defects in the propagation and amplification of the traveling wave in Gas2 mutants. We propose that the microtubule bundling activity of GAS2 imparts supporting cells with mechanical properties for transmitting sound energy through the cochlea.

The objective of this study is to determine the variations in size and shape of the most widely recognized cochlear malformation types using three-dimensional (3D) visualization. Using 3D slicer freeware, the complete inner-ear structures were segmented from 46 anonymized high-resolution computed tomography (HRCT) image datasets. Cochlear height, internal auditory canal height, and width were measured from the axial plane. Cochlear basal turn diameter was measured from the oblique coronal plane. Number of cochlear turns was measured from the 3D images and the corresponding cochlear duct length (CDL) was estimated using the CDL equations given in Alexiades et al. [Otol Neurotol 36 (2015) 904-907]. Out of 46 preoperative HRCT image datasets of human temporal bone, cochlear anatomy types including normal anatomy (4), enlarged vestibular aqueduct syndrome (3), cochlear aplasia (2), incomplete partition Types I (8), II (Mondini's deformity) (3), and III (X-linked) (4), cochlear hypoplasia (CH) (17), and common cavity (CC) (5) were identified. Majority of CH cases had cochlear height shorter than 4 mm whereas the CC cases measured cochlear height above 6 mm. For all the other malformation types, cochlear height was between 4 and 6 mm. In terms of "A" value, majority of CH cases showed shorter "A" value of <7.5 mm, which is in the lower end in comparison to the rest of the malformation types reported in this study. 3D-visualization shows the size and shape variations of all the structures of inner ear and also improves the clinicians' ability to visualize cochlear anatomy and nearby structures much easier than from the 2D image slices. Anat Rec, 302:1792-1799, 2019. © 2019 The Author. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association for Anatomy.

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.