Calculation of the Faradaic Impedance of the Electrode-Tissue Interface Improves Prediction of Behavioral T/C Levels in Cochlear Implant Patients.

BACKGROUND: Fitting of cochlear implants is a labor-intensive process, and therefore automated fitting procedures are being sought. The objective of this study was to evaluate if decomposition of the complex impedance of the electrode-tissue interface could provide additional parameters that show improved correlation with the behavioral T/C levels. METHODS: A new method for decomposing the complex impedance of the electrode-tissue interface was developed and tested in 18 patients in a prospective study in a tertiary otologic referral center. RESULTS: The averaged near-field Faradaic resistance (RF) calculated in study subjects shows a very strong correlation (R2=0.80) with the behavioral C levels and can be used for automated fitting in most patients. The standard deviation for the T levels and the C levels calculated for each of the electrode contacts in all study subjects is in the range of 10-15 CL and 15-20 CL, respectively. These higher values of the standard deviations are caused by a few outliers who require that additional parameters have to be added to the metric equation, allowing for the automated prediction of the T/C levels. CONCLUSION: A new method for deriving information from the electrode impedance measurements shows excellent correlation of the Faradaic resistance with the behavioral T/C levels in most patients and can be very useful for fitting cochlear implants based on objective measures. Since some patients still show discrepancies between the predicted T/C levels based on the RF calculation, additional parameters have to be added to the metric equation, allowing for automated prediction of the T/C levels.

Cochlear implant electrode array tip-foldover detection by electrode voltage telemetry.

OBJECTIVES: With the introduction of more flexible and thinner electrodes, such as Cochlear's Slim Modiolar Electrode, there is a higher risk of electrode insertion problems, in particular the tip foldover. Timely intraoperative detection of the problem would allow for direct intraoperative correction. This paper describes a non-radiological method for intraoperative tip foldover detection that is applicable in all surgical centers and can quickly deliver accurate results. METHODS: Postoperative radiographs of 118 CI-recipients implanted with Nucleus devices were retrospectively analyzed on the presence of a tip foldover. Electrode Voltage Telemetry (EVT), also called Electric Field Imaging, was performed by means of Cochlear's EVT software tool, which is now integrated into Custom Sound-EP as the Trans-Impedance-Matrix measurement option. Tip foldover detection was automated by using the linear Hough transform for extracting straight-line patterns in the Trans-Impedance Matrix's heatmap. RESULTS: The six cases of electrode tip foldover were accurately identified by the EVT measurements, including two cases with folding location very close to the electrode tip (contact 20). CONCLUSION: Electrode Voltage Telemetry measures the Trans-Impedance Matrix, which can accurately detect tip foldovers of the cochlear implant electrodes within 1 min. This method can be reliably applied in all patients with normal cochlear anatomy and is able to intraoperatively detect foldovers localized even very close to the electrode tip. Application of the linear Hough transform allows for automatic detection of electrode tip foldovers that shows excellent agreement with visual evaluation of the radiological images and the transimpedance matrix's heatmap.

Novel Impedance Measures as Biomarker for Intracochlear Fibrosis.

Measurement of the complex electrical impedance of the electrode contacts can provide new insights into the factors playing a role in the preservation of residual hearing with cochlear implants (CIs). However, unraveling the contributions related to the different phenomena from impedance data necessitates more advanced measurement and analysis techniques. The present study explores a new impedance measurement option recently included into the cochlear-implant programming software and aims to contribute to a more solid basis for the clinical use of impedance measures as a biomarker for fibrous tissue formation. Twenty adult CI-recipients were followed from surgery until 1 year after implantation by means of Electrode Voltage Telemetry (EVT), also called Electric Field Imaging or TransImpedance-Matrix measurement, and a 4-point technique for probing the voltage between adjacent electrode contacts. The data were compared to the electrode location derived from computed tomography, and to the device usage log. Using our impedance model for electrical stimulation of the cochlea, the polarization impedance related the electrode-tissue interface was determined, and the bulk impedance (access resistance) was split into a near-field and a far-field component. On average, the polarization impedance increased abruptly after surgery, indicating a strong passivation of the electrode contacts before cochlear-implant initiation. Its initial rise resolved almost completely soon after device switchon (2-4 weeks). The gradual increase of the access resistance mainly happened during the first 40 days on a time scale very similar to that observed in a guinea-pig study correlating impedance changes to fibrous tissue growth. The higher increase towards the round window is consistent with the higher amount of tissue observed in histological animal studies close to the electrode entry point. While the initial changes were due to the near-field resistance, the far-field resistance began to rise only after one month for half of the study group, once the near-field component had reached its critical value. This suggests indeed fibrosis initiating near the electrode contacts and spreading thereafter farther away. The near-field resistance positively correlated to device usage. EVT data allow for a further decomposition of the impedance at a cochlear-implant electrode, yielding a more detailed description of the postoperative intracochlear phenomena, such as fibrosis.

3D-localisation of cochlear implant electrode contacts in relation to anatomical structures from in vivo cone-beam computed tomography.

Positioning of the cochlear implant (CI) electrode in relation to the anatomical structures is a key factor for the hearing outcome and the preservation of residual hearing after cochlear implantation. Determining the exact electrode's location is therefore expected to play an important role in optimisation of the electrode design, the surgical techniques and the post-operative device fitting. The aim of this study is the development and validation of a robust and efficient computerised algorithm for three-dimensional (3D) localisation of the CI-electrode contacts with respect to the relevant cochlear structures, such as the basilar membrane and the modiolus, from modern clinical in vivo cone-beam computed tomography (CBCT). In the presented algorithm, the pre- and post-implantation CBCT are spatially aligned. To localise the anatomical structures, a cochlear microanatomical template derived from lab-based X-ray computed microtomography (µCT) measurements is warped to match the patient-specific cochlear shape acquired from pre-implantation CBCT. The electrode-contact locations, determined from the post-operative CBCT, are superimposed onto the cochlear fine-structure of the microanatomical template to localise the array. The accuracy of this method was validated in a temporal bone study by comparing the distance of the electrode contacts from the modiolar wall, as derived by the algorithm from CBCTs, with the distance determined from synchrotron-radiation (SR) µCT on the same specimens. Due to the achievable spatial resolution, good tissue contrast and limited presence of metallic artifacts, the SRµCT technique is considered to be a golden standard in the proposed approach. In contrast to other approaches, this validation method allowed for the evaluation of the final electrode-to-modiolus distance (EMD) error, and covers the error in co-alignment of the images, in the determination of the electrode contact location and in the localisation of the cochlear structures. The absolute mean error on the EMD parameter was determined at 0.11 mm (max = 0.29 mm, SD = 0.07 mm) across five samples, slightly lower than the voxel size of the CBCT-scans. In a retrospective study, the algorithm was applied to identify scalar translocations of the electrode from clinical in vivo CBCT datasets of 23 CI-recipients, which showed perfect (100%) agreement with the blinded opinion of two experienced neuroradiologists.

Vestibular Co-stimulation in Adults with a Cochlear Implant.

BACKGROUND: Vestibular co-stimulation is a side effect of cochlear implant stimulation. The electrical currents delivered by the cochlear implant can spread toward the vestibular system and thus stimulate it. The aim of the study is to evaluate whether it is feasible to functionally restore the balance by modifying the vestibular co-stimulation. METHODS: Four adult patients, who had received a commercially available cochlear implant previously, were enrolled. Counterbalanced biphasic pulses were presented as bursts or as an amplitude-modulated biphasic pulse train (modulation frequencies ranging from 1 to 500 Hz) at the participant's upper comfortable level for electrical stimulation. Subjective sensations and vestibular-mediated eye movements were used for evaluating the possible effects of vestibular co-stimulation. RESULTS: One participant experienced a cyclic tilting of his head in response to an amplitude-modulated biphasic pulse train with a modulation frequency of 2 and 400 Hz. However, during a follow-up visit, the sensation could not be replicated. CONCLUSION: Subjective vestibular sensations or vestibular-mediated eye movements could not be electrically evoked with a commercially available cochlear implant in 4 adult patients with almost normal vestibular function. Therefore, customized design of the hard-, firm-, and/or software of the commercially available cochlear implant might be necessary in order to electrically restore vestibular performance.

Prognostic Value of Trial Round Window Stimulation for Selection of Candidates for Cochlear Implantation as Treatment for Tinnitus.

Electrical stimulation with cochlear implants is able to significantly suppress the tinnitus sensations in 25-72% of implanted patients. Up to this point, no clear predictors for the effectiveness of tinnitus suppression with cochlear implants have been found and this substantially limits the possibility of the application of cochlear implants for this purpose. The objective of the study was to investigate if a trial electrical round window stimulation (RWS) could be used as a diagnostic tool for identifying candidates in whom electrical stimulation would be successful as treatment for tinnitus. Thirty-four patients with unilateral severe tinnitus and ipsilateral moderate to severe sensorineural hearing loss underwent a trial RWS under local anesthesia. Thirteen patients received a cochlear implant. All patients qualified for cochlear implantation on the basis of the trial RWS showed tinnitus suppression with the implant switched on. Complete or almost complete tinnitus suppression was obtained in 77% and partial in 23%. The mean tinnitus loudness reduction was 68% (VAS score reduction from 7.7 to 2.5). False negative results are estimated not to exceed 10-15%. We conclude that significant tinnitus suppression achieved during trial RWS under local anesthesia is a simple procedure allowing the efficient identification of candidates in whom electrical stimulation with a cochlear implant would be successful as treatment for intractable tinnitus.

Synchrotron radiation X-ray microtomography for the visualization of intra-cochlear anatomy in human temporal bones implanted with a perimodiolar cochlear implant electrode array.

Recently, synchrotron radiation computed microtomography (SRµCT) has emerged as a promising tool for non-destructive, in situ visualization of cochlear implant electrode arrays inserted into a human cochlea. Histological techniques have been the `gold standard' technique for accurate localization of cochlear implant electrodes but are suboptimal for precise three-dimensional measurements. Here, an SRµCT experimental setup is proposed that offers the benefit of a high spatial and contrast resolution (isotropic voxel size = 4.95 µm and propagation-based phase-contrast imaging), while visualizing the soft-tissue structures and electrode array of the cochlear implant simultaneously. In this work, perimodiolar electrode arrays have been tested, which incorporate thick and closely spaced platinum-iridium contacts and wiring. These data can assist cochlear implant and hearing research, can be used to verify electrode segmentation techniques for clinical computed tomography or could be utilized to evaluate cochlear implant electrode array designs.

Objective Acoustic Quantification of Perceived Voice Tremor Severity.

Purpose This study compared auditory-perceptual measures of presence/absence and severity of vocal tremor to acoustic markers of vocal tremor. The validity (both concurrent and diagnostic) of various acoustic markers of vocal tremor was also assessed. Method Fifty-six midvowel sustained [a:] recordings were selected to yield a representative convenience sample of vocal tremor. After training with 10 synthesized samples, 4 female audiologists rated these samples on "voice tremor severity" on a continuous 10-cm scale. Afterward, 15 randomly selected recordings were presented a 2nd time for intrarater reliability assessment. Customized audio signal processing in Praat yielded 12 acoustic measures of rate, extent and perturbation of fundamental frequency (f 0), and intensity level (IL) modulation. Enter-type multiple linear regression analysis was applied to weight and combine these acoustic variables into an acoustic model of vocal tremor severity. Results After removing the vocal tremor severity ratings of 1 of the audiologists because of insufficient intra- and interrater reliability, mean single-measures consistency-type intraclass correlation coefficients equaled .83 within raters and .72 between raters. Correlation between mean ratings and the 12 acoustic markers ranged from .76 for median extent of f 0 modulation to .11 for rate of IL modulation. Correlation between mean ratings and the acoustic model was .89. Analysis of this model's receiver operating characteristics yielded an area under receiver operating characteristic curve of .93, denoting sensitivity of .87 and specificity of .91. Conclusions This study demonstrated that auditory-perceptual ratings of vocal tremor severity are guided primarily by f 0 and IL modulation extent, less by modulation perturbation, and least by modulation rate. The acoustic model covering all these modulation properties yielded acceptable results in terms of both concurrent and diagnostic validity. However, external cross-validation of this model is warranted before applying it in clinical voice/speech assessment.

Layer-by-layer coated digitally encoded microcarriers for quantification of proteins in serum and plasma.

The "layer-by-layer" (LbL) technology has been widely investigated for the coating of flat substrates and capsules with polyelectrolytes. In this study, LbL polyelectrolyte coatings applied at the surface of digitally encoded microcarriers were evaluated for the quantitative, sensitive, and simultaneous detection of proteins in complex biological samples like serum, plasma, and blood. LbL coated microcarriers were therefore coupled to capture antibodies, which were used as capture agents for the detection of tumor necrosis factor (TNF-alpha), P24, and follicle stimulating hormone (FSH). It was found that the LbL coatings did not disassemble upon incubating the microcarriers in serum and plasma. Also, nonspecific binding of target analytes to the LbL coating was not observed. We showed that the LbL coated microcarriers can reproducibly detect TNF-alpha, P24, and FSH down to the picogram per milliliter level, not only in buffer but also in serum and plasma samples. Microcarrier-to-microcarrier intratube variations were less then 30%, and interassay variations less than 8% were observed. This paper also shows evidence that the LbL coated digitally encoded microcarriers are ideally suited for assaying proteins in "whole" blood in microfluidic chips, which are of high interest for "point-of-care" diagnostics.

Encoding microcarriers by spatial selective photobleaching.

Bead-based assays on very large numbers of molecules in gene expression studies, drug screening and clinical diagnostics, require the encoding of each of the microspheres according to the particular ligand bound to its surface. This allows mixing the uniquely encoded microspheres and subjecting them to an assay simultaneously. When a particular microsphere gives a positive reaction, the substance on its surface can be identified by reading the code. Previously reported techniques for colour encoding polymer microspheres only allow for a limited number of unique codes. Graphical encoding methods use metallic particles, which are rather uncommon in screening applications. Here, we demonstrate a new approach to encode polymer microspheres that are commonly used in screening applications, such as polystyrene microspheres, with a method that provides a virtually unlimited number of unique codes. Patterns can be written in fluorescently dyed microspheres by 'spatial selective photobleaching' and can be identified by confocal microscopy. Such encoded microparticles can find broad application in the collection and analysis of genetic information, high-throughput screening, medical diagnostics and combinatorial chemistry, and can also be used for labelling of consumer goods or as security labels to prevent counterfeiting.

Encoding microcarriers: present and future technologies.

In answer to the ever-increasing need to carry out many assays simultaneously in drug screening and drug discovery, several microcarrier-based multiplex technologies have arisen in the past few years. The compounds to be screened are attached to the surface of microcarriers, which can be mixed together in a vessel that contains the target analyte. Each microcarrier has to be encoded to know which compound is attached to its surface. In this article, the methods that have been developed for the encoding of microcarriers are reviewed and discussed.