Computational Evaluation of Cochlear Implant Surgery Outcomes Accounting for Uncertainty and Parameter Variability.

Cochlear implantation (CI) is a complex surgical procedure that restores hearing in patients with severe deafness. The successful outcome of the implanted device relies on a group of factors, some of them unpredictable or difficult to control. Uncertainties on the electrode array position and the electrical properties of the bone make it difficult to accurately compute the current propagation delivered by the implant and the resulting neural activation. In this context, we use uncertainty quantification methods to explore how these uncertainties propagate through all the stages of CI computational simulations. To this end, we employ an automatic framework, encompassing from the finite element generation of CI models to the assessment of the neural response induced by the implant stimulation. To estimate the confidence intervals of the simulated neural response, we propose two approaches. First, we encode the variability of the cochlear morphology among the population through a statistical shape model. This allows us to generate a population of virtual patients using Monte Carlo sampling and to assign to each of them a set of parameter values according to a statistical distribution. The framework is implemented and parallelized in a High Throughput Computing environment that enables to maximize the available computing resources. Secondly, we perform a patient-specific study to evaluate the computed neural response to seek the optimal post-implantation stimulus levels. Considering a single cochlear morphology, the uncertainty in tissue electrical resistivity and surgical insertion parameters is propagated using the Probabilistic Collocation method, which reduces the number of samples to evaluate. Results show that bone resistivity has the highest influence on CI outcomes. In conjunction with the variability of the cochlear length, worst outcomes are obtained for small cochleae with high resistivity values. However, the effect of the surgical insertion length on the CI outcomes could not be clearly observed, since its impact may be concealed by the other considered parameters. Whereas the Monte Carlo approach implies a high computational cost, Probabilistic Collocation presents a suitable trade-off between precision and computational time. Results suggest that the proposed framework has a great potential to help in both surgical planning decisions and in the audiological setting process.

Towards a Complete In Silico Assessment of the Outcome of Cochlear Implantation Surgery.

Cochlear implantation (CI) surgery is a very successful technique, performed on more than 300,000 people worldwide. However, since the challenge resides in obtaining an accurate surgical planning, computational models are considered to provide such accurate tools. They allow us to plan and simulate beforehand surgical procedures in order to maximally optimize surgery outcomes, and consequently provide valuable information to guide pre-operative decisions. The aim of this work is to develop and validate computational tools to completely assess the patient-specific functional outcome of the CI surgery. A complete automatic framework was developed to create and assess computationally CI models, focusing on the neural response of the auditory nerve fibers (ANF) induced by the electrical stimulation of the implant. The framework was applied to evaluate the effects of ANF degeneration and electrode intra-cochlear position on nerve activation. Results indicate that the intra-cochlear positioning of the electrode has a strong effect on the global performance of the CI. Lateral insertion provides better neural responses in case of peripheral process degeneration, and it is recommended, together with optimized intensity levels, in order to preserve the internal structures. Overall, the developed automatic framework provides an insight into the global performance of the implant in a patient-specific way. This enables to further optimize the functional performance and helps to select the best CI configuration and treatment strategy for a given patient.

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.

Automatic Model Generation Framework for Computational Simulation of Cochlear Implantation.

Recent developments in computational modeling of cochlear implantation are promising to study in silico the performance of the implant before surgery. However, creating a complete computational model of the patient's anatomy while including an external device geometry remains challenging. To address such a challenge, we propose an automatic framework for the generation of patient-specific meshes for finite element modeling of the implanted cochlea. First, a statistical shape model is constructed from high-resolution anatomical µCT images. Then, by fitting the statistical model to a patient's CT image, an accurate model of the patient-specific cochlea anatomy is obtained. An algorithm based on the parallel transport frame is employed to perform the virtual insertion of the cochlear implant. Our automatic framework also incorporates the surrounding bone and nerve fibers and assigns constitutive parameters to all components of the finite element model. This model can then be used to study in silico the effects of the electrical stimulation of the cochlear implant. Results are shown on a total of 25 models of patients. In all cases, a final mesh suitable for finite element simulations was obtained, in an average time of 94 s. The framework has proven to be fast and robust, and is promising for a detailed prognosis of the cochlear implantation surgery.

Patient-specific simulation of implant placement and function for cochlear implantation surgery planning.

We present a framework for patient specific electrical stimulation of the cochlea, that allows to perform in-silico analysis of implant placement and function before surgery. A Statistical Shape Model (SSM) is created from high-resolution human µCT data to capture important anatomical details. A Finite Element Model (FEM) is built and adapted to the patient using the results of the SSM. Electrical simulations based on Maxwell's equations for the electromagnetic field are performed on this personalized model. The model includes implanted electrodes and nerve fibers. We present the results for the bipolar stimulation protocol and predict the voltage spread and the locations of nerve excitation.

Functional simulation of the cochlea for implant optimization.

Cochlear implantation is a surgical technique which aims to restore hearing in people with deep hearing loss. However, outcomes of the surgery still exhibit a large variability between patients. Among the factors that contribute to variability the most important are morphological differences in anatomical structures between patients and incorrect implant placements. In order to address these issues, it would be desirable to have a functional model of the cochlea which incorporates inter-patients variability and simulate electrode placement. To this end, we present a finite element model which captures the interaction between the cochlear partition, modeled as an elastic solid with finite deformation, and the perilymph fluid, modeled as a compressible, viscous fluid. Numerical results show that the membrane responds to changes in the stimulation frequencies.

The role of potassium recirculation in cochlear amplification.

PURPOSE OF REVIEW: Normal cochlear function depends on maintaining the correct ionic environment for the sensory hair cells. Here we review recent literature on the cellular distribution of potassium transport-related molecules in the cochlea. RECENT FINDINGS: Transgenic animal models have identified novel molecules essential for normal hearing and support the idea that potassium is recycled in the cochlea. The findings indicate that extracellular potassium released by outer hair cells into the space of Nuel is taken up by supporting cells, that the gap junction system in the organ of Corti is involved in potassium handling in the cochlea, that the gap junction system in stria vascularis is essential for the generation of the endocochlear potential, and that computational models can assist in the interpretation of the systems biology of hearing and integrate the molecular, electrical, and mechanical networks of the cochlear partition. Such models suggest that outer hair cell electromotility can amplify over a much broader frequency range than expected from isolated cell studies. SUMMARY: These new findings clarify the role of endolymphatic potassium in normal cochlear function. They also help current understanding of the mechanisms of certain forms of hereditary hearing loss.

Histidine 518 in the S6-CNBD linker controls pH dependence and gating of HCN channel from sea-urchin sperm.

Sperm motility is a tightly regulated process. One of the crucial factors determining the swimming of the sea-urchin sperm is an elevation of intracellular pH (pH(i)). The possibility that its hyperpolarisation-activated cyclic nucleotide-gated channel (SpHCN) is modulated directly by pH is addressed here. Site-directed mutagenesis showed that histidine 518 from the linker connecting the S6 helix with the cyclic nucleotide binding domain is responsible for the pH modulation of current kinetics and voltage dependence of activation. The effect of mutating histidine 518 to serine (H518S) on the time constant of activation was maximal at pH 6.4: 180+/-20 ms in the wild-type (wt) but only 56+/-10 ms in the H518S mutant channel. Furthermore, histidine 518 accounted for 31% of the shift in the voltage of half activation ( V(1/2)) in wt following a pH change from 6.4 to 8.4. The mutation H518S also shifted V(1/2) by 19 mV at pH 7.4 (-50.2+/-0.2 and -69+/-2 mV for H518S and wt, respectively). This indicates that histidine 518 couples voltage sensing to gating. The wt and H518S channels had a different affinity for cyclic adenosine monophosphate (cAMP) (IC(50) 1.0+/-0.02 and 2.5+/-0.06 microM, respectively). Changes in pH(i) also modulated channel selectivity.

Pore topology of the hyperpolarization-activated cyclic nucleotide-gated channel from sea urchin sperm.

The current flow through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, referred to as I(h), plays a major role in several fundamental biological processes. The sequence of the presumed pore region of HCN channels is reminiscent of that of most known K(+)-selective channels. In the present work, the pore topology of an HCN channel from sea urchin sperm, called SpHCN, was investigated by means of the substituted-cysteine accessibility method (SCAM). The I(h) current in the wild-type (w.t.) SpHCN channel was irreversibly blocked by intracellular Cd(2+). This blockage was not observed in mutant C428S. Extracellular Cd(2+) did not cause any inhibition of the I(h) current in the w.t. SpHCN channel, but blocked the current in mutant channels K433C and F434C. Large extracellular anions blocked the current both in the w.t. and K433Q mutant channel. These results suggest that 1) cysteine in position 428 faces the intracellular medium; 2) lysine and phenylalanine in position 433 and 434, respectively, face the extracellular side of the membrane; and 3) lysine 433 does not mediate the anion blockade. Additionally, our study confirms that the K(+) channel signature sequence GYG also forms the inner pore in HCN channels.