Investigation of auditory neuronal survival and outgrowth using a cochlear implant in an artificial cochlear model

Cochlear implants (CI) can restore hearing to people suffering from sensorineural hearing loss. The CI uses an array of electrodes inserted in the scala tympani to stimulate the spiral ganglion neurons (SGN), which are located in the bony axis of the inner ear. The spatial distance between the electrodes and the SGN results in spread of excitation and unfocused stimulation. This distance could be bypassed by a neurite outgrowth towards the CI. In order to establish a culture system for the development of novel strategies for CI optimization, a neurite outgrowth chamber (NOC) allowing clinically relevant electrical stimulation paradigms was developed using fused deposition modelling. It was made out of biocompatible UV-curing silicone. The NOC was equipped with a slot to insert the electrode array into a scala tympani compartment whereas SGN isolated from postnatal rats were cultured in a neighbouring region mimicking the Rosenthal’s canal. Sound delivered through loudspeakers playing a radio program was captured by the CI sound processor, positioned outside the NOC, for 17 hours daily during a four-day period. The NOCs were tightly sealed and the electrode array could be positioned in the scala tympani compartment. The experimental setup allowed cell cultivation and the stimulation resulted in a significantly increased neurite length of around 36% while explant area and neurite number did not differ to the negative control (NC). A new in vitro testing system which considers the anatomy of the cochlea and clinic stimulation conditions has been developed and validated. The validation experiments resulted in increased neurite length. This indicates a progress in bridging the anatomical gap between electrode and stimulated neurons.

Cochlear Size Assessment Predicts Scala Tympani Volume and Electrode Insertion Force- Implications in Robotic Assisted Cochlear Implant Surgery

Objectives: The primary aim was to measure the volume of the scala tympani (ST) and the length of the straight portion of the cochlear basal turn from micro-computed tomography (μCT) images. The secondary aim was to estimate the electrode insertion force based on cochlear size and insertion speed. Both of these objectives have a direct clinical relevance in robotic assisted cochlear implant (CI) surgery.Methods: The ST was segmented in thirty μCT datasets to create a three-dimensional (3D) model and calculate the ST volume. The diameter (A-value), the width (B-value), and the straight portion of the cochlear basal turn (S-value) were measured from the oblique coronal plane. Electrode insertion force was measured in ST models of two different sizes, by inserting FLEX24 (24 mm) and FLEX28 (28 mm) electrode arrays at five different speeds (0.1, 0.5, 1, 2, and 4 mm/s).Results: The mean A-, B-, and S-values measured from the 30 μCT datasets were 9.0 ± 0.5, 6.7 ± 0.4, and 6.9 mm ± 0.5, respectively. The mean ST volume was 34.2 μl ± 7 (range 23–50 μl). The ST volume increased linearly with an increase in A- and B-values (Pearson's coefficient r = 0.55 and 0.56, respectively). The A-value exhibited linear positive correlation with the B-value and S-value (Pearson's coefficient r = 0.64 and r = 0.66, respectively). In the smaller of the two ST models, insertion forces were higher across the range of insertion speeds during both array insertions, when compared to the upscaled model. Before the maximum electrode insertion depths, a trend toward lower insertion force for lower insertion speed and vice-versa was observed.Conclusion: It is important to determine pre-operative cochlear size as this seems to have an effect upon electrode insertion forces. Higher insertion forces were seen in a smaller sized ST model across two electrode array lengths, as compared to an upscaled larger model. The ST volume, which cannot be visualized on clinical CT, correlates with clinical cochlear parameters. This enabled the creation of an equation capable of predicting ST volume utilizing A- and B-values, thus enabling pre-operative prediction of ST volume.

Effects of in vivo repositioning of slim modiolar electrodes on electrical thresholds and speech perception

The slim modiolar electrode has been reported to ensure better modiolar proximity than previous conventional perimodiolar electrodes and consistently high scala tympani localization. Nonetheless, variability in modiolar proximity exists even among slim modiolar electrodes, still leaving room for further improvement of modiolar proximity, which may positively affect functional outcomes. Given this, the pull-back maneuver was reported to increase the modiolar proximity of slim modiolar electrodes in a cadaveric study, but in vivo repositioning effects remain to be established. Here we identified that the pull-back maneuver led to better modiolar proximity than conventional insertion while maintaining a similar angular insertion depth. Notably, the reduced electrode-modiolus distance from the pull-back maneuver was associated with significantly lower impedances across electrodes postoperatively as well as reduced intraoperative electrophysiological thresholds than conventional insertion. Among adult cochlear implant recipients, this maneuver resulted in significantly better sentence recognition scores at three months postoperatively when compared to those with a conventional insertion; however, this benefit was not observed at later intervals. Collectively, slim modiolar electrodes with the pull-back maneuver further enhance the modiolar proximity, possibly leading to better open-set sentence recognition, at least in the early postoperative stage.

Atraumatic Insertion of a Cochlear Implant Pre-Curved Electrode Array by a Robot-Automated Alignment with the Coiling Direction of the Scala Tympani

<b><i>Introduction:</i></b> Electrode array translocation is an unpredictable event with all types of arrays, even using a teleoperated robot in a clinical scenario. We aimed to compare the intracochlear trauma produced by the HiFocus™ Mid-Scala (MS) electrode array (Advanced Bionics, Valencia, CA, USA) using a teleoperated robot, with an automated robot connected to a navigation system to align the pre-curved tip of the electrode array with the coiling direction of the scala tympani (ST). <b><i>Methods:</i></b> Fifteen freshly frozen temporal bones were implanted with the MS array using the RobOtol® (Collin, Bagneux, France). In the first group (<i>n</i> = 10), the robot was teleoperated to insert the electrode array into the basal turn of the ST under stereomicroscopic vision, and then the array was driven by a slow-speed hydraulic insertion technique with an estimated placement of the pre-curved electrode tip. In the second group (<i>n</i> = 5), 3 points were obtained from the preoperative cone-beam computed tomography: the 2 first defining the ST insertion axis of the basal turn and a third one at the center of the ST at 270°. They provided the information to the automated system (RobOtol® connected with a navigation system) to automatically align the electrode array with the ST insertion axis and to aim the pre-curved tip toward the subsequent coiling of the ST. After this, the electrode array was manually advanced. Finally, the cochleae were obtained and fixed in a crystal resin, and the position of each electrode was determined by a micro-grinding technique. <b><i>Results:</i></b> In all cases, the electrode array was fully inserted into the cochlea and the depth of insertion was similar using both techniques. With the teleoperated robotic technique, translocations of the array were observed in 7/10 insertions (70%), but neither trauma nor array translocation occurred with automated robotic insertion. <b><i>Conclusion:</i></b> We have successfully tested an automated insertion system (robot + navigation) that could accurately align a pre-curved electrode array to the axis of the basal turn of the ST and its subsequent coiling, which reduced intracochlear insertion trauma and translocation.

RAT COCHLEA CONTINUES TO DEVELOP AFTER BIRTH

Introduction: The ear, originates from the ectoderm, exhibits a complex structure that differs from species to species in terms of development. Objectives: This study was conducted to describe the prenatal and postnatal development process of the organ of Corti in the iner ear using light microscopy. Methods: In this study, Wistar Albino rats were used. The rats were divided into two groups as prenatal and postnatal groups. Prenatal groups consisting of embryos on day 17, 19, 21 and postnatal groups consisting of pups on days 1, 5, 10 and 15. The rats were sacrificed to investigate the cochleas by light microscopy. Results: The lumen of the cochlear tunnel was lined with pseudostratified columnar epithelia throughout the prenatal period. The cochlear tunnel was not divided into scala media, scala tympani and scala vestibuli in the embryonic sections. Organ of corti hasn’t taken its final form until postnatal day 15. Conclusion: In rats, formation of organ of Corti is completed in postnatal 15 day. Pups of rats are not able to hear in the embronic and early postnatal life.

Uncoiling the Human Cochlea—Physical Scala Tympani Models to Study Pharmacokinetics Inside the Inner Ear

In the field of cochlear implantation, artificial/physical models of the inner ear are often employed to investigate certain phenomena like the forces occurring during implant insertions. Up to now, no such models are available for the analysis of diffusion processes inside the cochlea although drug delivery is playing an increasingly important role in this field. For easy access of the cochlea along its whole profile, e.g., for sequential sampling in an experimental setting, such a model should ideally be longitudinal/uncoiled. Within this study, a set of 15 micro-CT imaging datasets of human cochleae was used to derive an average representation of the scala tympani. The spiral profile of this model was then uncoiled along different trajectories, showing that these trajectories influence both length and volume of the resulting longitudinal model. A volumetric analysis of the average spiral model was conducted to derive volume-to-length interrelations for the different trajectories, which were then used to generate two tubular, longitudinal scala tympani models with volume and length properties matching the original, spiral profile. These models can be downloaded for free and used for reproducible and comparable simulative and experimental investigations of diffusion processes within the inner ear.

Computed-tomography estimates of interaural mismatch in insertion depth and scalar location in bilateral cochlear-implant users

Hypothesis: We hypothesized that the bilateral cochlear-implant (BI-CI) users would have a range of interaural insertion-depth mismatch because of different physical placements or characteristics of the arrays, but less than half of electrodes would have less than 75° or 3 mm of interaural insertion-depth mismatch. We also hypothesized that interaural insertion-depth mismatch would be more prevalent nearer the apex, when electrodes were located outside of scala tympani (i.e., possible interaural scalar mismatch), and when the arrays were a mix of pre-curved and straight types. Background: Brainstem neurons in the superior olivary complex are exquisitely sensitive to interaural differences, the cues to sound localization. These binaurally sensitive neurons rely on interaurally place-of-stimulation-matched inputs at the periphery. BI-CI users may have interaural differences in insertion depth and scalar location, causing interaural place-of-stimulation mismatch that impairs binaural abilities. Methods: Insertion depths and scalar locations were calculated from temporal-bone computed-tomography (CT) scans of 107 BI-CI users (27 Advanced Bionics, 62 Cochlear, and 18 Med-El). Each subject had either both pre-curved, both straight, or one of each type of array (mixed). Results: The median interaural insertion-depth mismatch was 23.4° or 1.3 mm. Relatively large interaural insertion-depth mismatch sufficient to disrupt binaural processing occurred for about 15% of electrode pairs [defined as >75° (13.0% of electrode pairs) or >3 mm (19.0% of electrode pairs)]. There was a significant three-way interaction of insertion depth, scalar location, and array type. Interaural insertion-depth mismatch was most prevalent when electrode pairs were more apically located, electrode pairs had interaural scalar mismatch (i.e., one in Scala Tympani, one in Scala Vestibuli), and when the arrays were both pre-curved. Conclusion: Large interaural insertion-depth mismatch can occur in BI-CI users. For new BI-CI users, improved surgical techniques to avoid interaural insertion-depth and scalar mismatch is recommended. For existing BI-CI users with interaural insertion-depth mismatch, interaural alignment of clinical frequency allocation tables by an audiologist might remediate any negative consequences to spatial-hearing abilities.

Microimaging of a novel intracochlear drug delivery device in combination with cochlear implants in the human inner ear

The effective delivery of drugs to the inner ear is still an unmet medical need. Local controlled drug delivery to this sensory organ is challenging due to its location in the petrous bone, small volume, tight barriers, and high vulnerability. Local intracochlear delivery of drugs would overcome the limitations of intratympanic (extracochlear) and systemic drug application. The requirements for such a delivery system include small size, appropriate flexibility, and biodegradability. We have developed biodegradable PLGA-based implants for controlled intracochlear drug release that can also be used in combination with cochlear implants (CIs), which are implantable neurosensory prosthesis for hearing rehabilitation. The drug carrier system was tested for implantation in the human inner ear in 11 human temporal bones. In five of the temporal bones, CI arrays from different manufacturers were implanted before insertion of the biodegradable PLGA implants. The drug carrier system and CI arrays were implanted into the scala tympani through the round window. Implanted temporal bones were evaluated by ultra-high-resolution computed tomography (µ-CT) to illustrate the position of implanted electrode carriers and the drug carrier system. The µ-CT measurements revealed the feasibility of implanting the PLGA implants into the scala tympani of the human inner ear and co-administration of the biodegradable PLGA implant with a CI array. Graphical abstract