The Dependency of Cochlear Lateral Wall Measurements on Observer and Imaging Type.

HYPOTHESIS: Assessment techniques for the cochlear spatial lateral wall are associated with inter-rater variability, but derived clinical recommendations nonetheless offer value for individualized electrode selection. BACKGROUND: Anatomical variations influence the location of cochlear implant electrodes inside the cochlea. Preoperative planning allows individualization of the electrode based on characterization of the bony lateral wall. METHODS: The study used publicly available digitized temporal bones based on microslicing and computed tomography. Four experienced observers assessed the lateral wall applying manual tracing, linear regression scaling and elliptic-circular approximation methods in all modalities. Radial and height differences were computed in 90-degree steps from the round window center to the apex. Total length, total angular length, and tonotopic frequencies were computed for each reconstruction. RESULTS: Differences were found most pronounced between assessment methods in vertical direction across observers and imaging modalities. One of the five anatomies was consistently found to be of shorter cochlear duct length with estimation techniques yielding more conservative results compared with manual tracings. CONCLUSIONS: Assessment techniques for the bony lateral wall yield method, observer, and image modality related deviations. Automation of the anatomical characterization may offer potential in minimizing inaccuracies. Nonetheless, observers were consistently able to detect a smaller inner ear demonstrating the ability of current methods to contribute to an optimized choice of electrodes based on individual patient anatomy.

3D-printing a cost-effective model for mastoidectomy training.

BACKGROUND: 3D-printed temporal bone models can potentially provide a cost-effective alternative to cadaver surgery that can be manufactured locally at the training department. The objective of this study was to create a cost-effective 3D-printed model suitable for mastoidectomy training using entry level and commercially available print technologies, enabling individuals, without prior experience on 3D-printing, to manufacture their own models for basic temporal bone training. METHODS: Expert technical professionals and an experienced otosurgeon identified the best material for replicating the temporal bone and created a cost-effective printing routine for the model using entry-level print technologies. Eleven participants at a temporal bone dissection course evaluated the model using a questionnaire. RESULTS: The 3D-printed temporal bone model was printed using a material extrusion 3D-printer with a heat resistant filament, reducing melting during drilling. After printing, a few simple post-processing steps were designed to replicate the dura, sigmoid sinus and facial nerve. Modifying the 3D-printer by installing a direct-drive and ruby nozzle resulted in more successful prints and less need for maintenance. Upon evaluation by otorhinolaryngology trainees, unanimous feedback was that the model provided a good introduction to the mastoidectomy procedure, and supplementing practice to cadaveric temporal bones. CONCLUSION: In-house production of a cost-effective 3D-printed model for temporal bone training is feasible and enables training institutions to manufacture their own models. Further, this work demonstrates the feasibility of creating new temporal bone models with anatomical variation to provide ample training opportunity.

OpenEar Image Data Enables Case Variation in High Fidelity Virtual Reality Ear Surgery.

BACKGROUND: Virtual reality (VR) simulation is an established option for temporal bone surgical training. Most VR simulators are based on computed tomography imaging, whereas the Visible Ear Simulator (VES) is based on high-fidelity cryosections of a single temporal bone specimen. Recently published OpenEar datasets combine cone-beam computed tomography (CBCT) and micro-slicing to achieve similar model quality. This study explores integration of OpenEar datasets into VES to enable case variation in simulation with implications for patient-specific modeling based on CBCT. METHODS: The OpenEar dataset consists of segmented, coregistered, multimodal imaging sets of human temporal bones. We derived drillable bone segments from the dataset as well as triangulated surface models of critical structures such as facial nerve or dura. Realistic visualization was achieved using coloring from micro-slicing, custom tinting, and texture maps. Resulting models were validated by clinical experts. RESULTS: Six of the eight OpenEar datasets could be integrated in VES complete with instructional guides for various temporal bone surgical procedures. Resulting models were of high quality because of postprocessing steps taken to increase realism including colorization and imaging artifact removal. Bone artifacts were common in CBCT, resulting in dehiscences that most often could not be found in the ground truth micro-slicing data. CONCLUSION: New anatomy models are included in VES version 3.5 freeware and provide case variation for training which could help trainees to learn more quickly and transferably under variable practice conditions. The use of CBCT for VR simulation models without postprocessing results in bone artifacts, which should be considered when using clinical imaging for patient-specific simulation, surgical rehearsal, and planning.

Measurement of the Intracochlear Hypothermia Distribution Utilizing Tympanic Cavity Hypothermic Rinsing Technique in a Cochlea Hypothermia Model.

Introduction: Cochlea implants can cause severe trauma leading to intracochlear apoptosis, fibrosis, and eventually to loss of residual hearing. Mild hypothermia has been shown to reduce toxic or mechanical noxious effects, which can result in inflammation and subsequent hearing loss. This paper evaluates the usability of standard surgical otologic rinsing as cooling medium during cochlea implantation as a potential hearing preservation technique. Material and Methods: Three human temporal bones were prepared following standard mastoidectomy and posterior tympanotomy. Applying a retrocochlear approach leaving the mastoidectomy side intact, temperature probes were placed into the basal turn (n = 4), the middle turn (n = 2), the helicotrema, and the modiolus. Temperature probe positions were visualized by microcomputed tomography (µCT) imaging and manually segmented using Amira® 7.6. Through the posterior tympanotomy, the tympanic cavity was rinsed at 37°C in the control group, at room temperature (in the range between 22 and 24°C), and at iced water conditions. Temperature changes were measured in the preheated temporal bone. In each temperature model, rinsing was done for 20 min at the pre-specified temperatures measured in 0.5-s intervals. At least five repetitions were performed. Data were statistically analyzed using pairwise t-tests with Bonferroni correction. Results: Steady-state conditions achieved in all three different temperature ranges were compared in periods between 150 and 300 s. Temperature in the inner ear started dropping within the initial 150 s. Temperature probes placed at basal turn, the helicotrema, and middle turn detected statistically significant fall in temperature levels following body temperature rinses. Irrigation at iced conditions lead to the most significant temperature drops. The curves during all measurements remained stable with 37°C rinses. Conclusion: Therapeutic hypothermia is achieved with standard surgical irrigation fluid, and temperature gradients are seen along the cochlea. Rinsing of 120 s duration results in a therapeutic local hypothermia throughout the cochlea. This otoprotective procedure can be easily realized in clinical practice.

Otoprotection to Implanted Cochlea Exposed to Noise Trauma With Dexamethasone Eluting Electrode.

Cochlear implantation (CI) is now widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, CI can lead to electrode insertion trauma (EIT) that can cause damage to sensory cells in the inner ear resulting in loss of residual hearing. Even with soft surgical techniques where there is minimal macroscopic damage, we can still observe the generation of molecular events that may initiate programmed cell death via various mechanisms such as oxidative stress, the release of pro-inflammatory cytokines, and activation of the caspase pathway. In addition, individuals with CI may be exposed to noise trauma (NT) due to occupation and leisure activities that may affect their hearing ability. Recently, there has been an increased interest in the auditory community to determine the efficacy of drug-eluting electrodes for the protection of residual hearing. The objective of this study is to determine the effect of NT on implanted cochlea as well as the otoprotective efficacy of dexamethasone eluting electrode to implanted cochlea exposed to NT in a guinea pig model of CI. Animals were divided into five groups: EIT with dexamethasone eluting electrode exposed to NT; EIT exposed to NT; NT only; EIT only and naïve animals (control group). The hearing thresholds were determined by auditory brainstem recordings (ABRs). The cochlea was harvested and analyzed for transcript levels of inflammation, apoptosis and fibrosis genes. We observed that threshold shifts were significantly higher in EIT, NT or EIT + NT groups compared to naive animals at all the tested frequencies. The dexamethasone eluting electrode led to a significant decrease in hearing threshold shifts in implanted animals exposed to NT. Proapoptotic tumor necrosis factor-α [TNF-α, TNF-α receptor 1a (TNFαR1a)] and pro-fibrotic transforming growth factor ß1 (TGFß) genes were more than two-fold up-regulated following EIT and EIT + NT compared to the control group. The use of dexamethasone releasing electrode significantly decreased the transcript levels of pro-apoptotic and pro-fibrotic genes. The dexamethasone releasing electrode has shown promising results for hearing protection in implanted animals exposed to NT. The results of this study suggest that dexamethasone releasing electrode holds great potential in developing effective treatment modalities for NT in the implanted cochlea.

The OpenEar library of 3D models of the human temporal bone based on computed tomography and micro-slicing.

Virtual reality surgical simulation of temporal bone surgery requires digitized models of the full anatomical region in high quality and colour information to allow realistic texturization. Existing datasets which are usually based on microCT imaging are unable to fulfil these requirements as per the limited specimen size, and lack of colour information. The OpenEar Dataset provides a library consisting of eight three-dimensional models of the human temporal bone to enable surgical training including colour data. Each dataset is based on a combination of multimodal imaging including Cone Beam Computed Tomography (CBCT) and micro-slicing. 3D reconstruction of micro-slicing images and subsequent registration to CBCT images allowed for relatively efficient multimodal segmentation of inner ear compartments, middle ear bones, tympanic membrane, relevant nerve structures, blood vessels and the temporal bone. Raw data from the experiment as well as voxel data and triangulated models from the segmentation are provided in full for use in surgical simulators or any other application which relies on high quality models of the human temporal bone.

A Novel Method for Clinical Cochlear Duct Length Estimation toward Patient-Specific Cochlear Implant Selection.

OBJECTIVE: 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. DESIGN: Retrospective analysis on cochlear length and shape in micro-computed tomography and cone beam computed tomography data. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: A simple 2-step approach was developed to accurately estimate the individual cochlear length as well as the projected length of an electrode array inside the cochlea. The method is capable of predicting the length of the cochlea and the inserted electrode length at any specific angle. Validation of the approach was performed with 20 scans of human temporal bones (micro-computed tomography) and 47 pre- and postoperative clinical scans (cone beam computed tomography). RESULTS: Mean ± SD absolute errors in cochlear length estimations were 0.12 ± 0.10 mm, 0.38 ± 0.26 mm, and 0.71 ± 0.43 mm for 1, 1.5, and 2 cochlea turns, respectively. Predicted insertion angles based on clinical cone beam computed tomography data showed absolute deviations of 27° ± 18° to the corresponding postoperative measurements. CONCLUSION: With accuracy improvements of 80% to 90% in comparison with previously proposed approaches, the method is well suited for the use in individualized cochlear implantation.

Challenging aspects of contemporary cochlear implant electrode array design.

OBJECTIVE: A design comparison of current perimodiolar and lateral wall electrode arrays of the cochlear implant (CI) is provided. The focus is on functional features such as acoustic frequency coverage and tonotopic mapping, battery consumption and dynamic range. A traumacity of their insertion is also evaluated. METHODS: Review of up-to-date literature. RESULTS: Perimodiolar electrode arrays are positioned in the basal turn of the cochlea near the modiolus. They are designed to initiate the action potential in the proximity to the neural soma located in spiral ganglion. On the other hand, lateral wall electrode arrays can be inserted deeper inside the cochlea, as they are located along the lateral wall and such insertion trajectory is less traumatic. This class of arrays targets primarily surviving neural peripheral processes. Due to their larger insertion depth, lateral wall arrays can deliver lower acoustic frequencies in manner better corresponding to cochlear tonotopicity. In fact, spiral ganglion sections containing auditory nerve fibres tuned to low acoustic frequencies are located deeper than 1 and half turn inside the cochlea. For this reason, a significant frequency mismatch might be occurring for apical electrodes in perimodiolar arrays, detrimental to speech perception. Tonal languages such as Mandarin might be therefore better treated with lateral wall arrays. On the other hand, closer proximity to target tissue results in lower psychophysical threshold levels for perimodiolar arrays. However, the maximal comfort level is also lower, paradoxically resulting in narrower dynamic range than that of lateral wall arrays. Battery consumption is comparable for both types of arrays. CONCLUSIONS: Lateral wall arrays are less likely to cause trauma to cochlear structures. As the current trend in cochlear implantation is the maximal protection of residual acoustic hearing, the lateral wall arrays seem more suitable for hearing preservation CI surgeries. Future development could focus on combining the advantages of both types: perimodiolar location in the basal turn extended to lateral wall location for higher turn locations.

Applicability of two automated disintegration apparatuses for rapidly disintegrating (mini)tablets.

OBJECTIVES: Orally disintegrating (mini)tablets (OD(M)Ts) are of interest in the field of pharmaceutics. Their orodispersible character is defined by the disintegration time, which is measured with a basket apparatus according to the European Pharmacopoeia. This method, however, lacks applicability for ODTs and especially ODMTs. New disintegration apparatuses have been described in literature, but a qualification to assess the applicability has not been described. A qualification procedure for two automated disintegration apparatuses, OD-mate and Hermes apparatus, is introduced. METHODS: Aspects of the operational qualification as well as precision and accuracy regarding a performance qualification were evaluated for both apparatuses analog to the ICH guideline Q2. While the OQ study is performed separately for each apparatus, accuracy and precision were performed following the same protocol for both testers. KEY FINDINGS: Small RSDs (16.9% OD-mate; 15.2% Hermes compared to 32.3% for the pharmacopeial method) were found despite very fast disintegration times (1.5 s for both apparatuses). By comparing these RSDs to practical examples, the authors propose threshold values for repeatability depending on the mean disintegration time. Obtained results from the qualification were used to assess the applicability of both apparatuses.

A new biorelevant dissolution method for orodispersible films.

Specific knowledge about the dissolution behavior under biorelevant conditions is of high interest for the rational development of orodispersible films (ODFs). As the conditions in the oral cavity strongly differ from those in the gastrointestinal tract and from those performed with the pharmacopoeial test setups, a biorelevant dissolution setup was developed in this work, considering the mechanical force of the tongue, the saliva flow, the small fluid volume and the saliva composition. Especially in the initial phase, dissolution profiles of KTP (ketoprofen) ODFs observed by the new method showed a slower drug release than obtained with setups based on conventional dissolution methods. 27.47% KTP release after 100s was detected using the new method, compared to 59.29-82.55% detected without considering the in vivo conditions. Furthermore, an influence of the simulated in vivo conditions on the dissolution profile was observed. By simulating either saliva flow or mechanical force, the KTP release after 100s was two to three times higher (18.78% and 14.18%) compared to the profiles, measured without considering one of the parameters (6.76%). Further studies have to show, whether obtained data are comparable to in vivo data to predict drug release profiles of ODFs in the oral cavity.