Trauma After Cochlear Implantation: The Accuracy of Micro-Computed Tomography and Cone-Beam Fusion Computed Tomography Compared With Histology in Human Temporal Bones.

HYPOTHESIS: Micro-computed tomography (micro-CT) and cone-beam computed tomography (CBCT), in conjunction with the image fusion technique, may provide similar results for trauma assessment after cochlear implantation, with respect to the trauma evaluation in preclinical cochlear implant (CI) studies, as the histology. BACKGROUND: Before clinical use, novel cochlear implant (CI) designs are tested in temporal bone (TB) studies for usability and risk evaluation. The criterion standard for evaluating intracochlear insertion trauma and electrode location has historically been with histological samples. Progress of modern imaging technology has created alternatives to classic histology. This study compares the micro-CT and CBCT fusion images between histological samples in a preclinical CI study. METHODS: Fourteen freshly frozen TBs were inserted with a lateral wall research CI electrode. All TBs were scanned with CBCT preoperatively and postoperatively. After insertion, the TBs were prepared for micro-CT and histology. Twelve TBs underwent first a micro-CT and then the histological process. The CBCTs were used for image fusion, and all three different methods were used for intracochlear trauma evaluation. The results were compared between methods. RESULTS: There were 4 of 14 translocations detected with the fusion image method and 3 of 12 with the micro-CT and histology. When compared, the trauma grades converged and were not statistically significant. CONCLUSION: The trauma grading based on micro-CT is comparable to the histology. The image fusion technique based on CBCT is less accurate because it relies on an empirical assumption of the basal membrane localization, but it is clinically applicable.

Anatomical Variations of the Human Cochlea Using an Image Analysis Tool.

Understanding cochlear anatomy is crucial for developing less traumatic electrode arrays and insertion guidance for cochlear implantation. The human cochlea shows considerable variability in size and morphology. This study analyses 1000+ clinical temporal bone CT images using a web-based image analysis tool. Cochlear size and shape parameters were obtained to determine population statistics and perform regression and correlation analysis. The analysis revealed that cochlear morphology follows Gaussian distribution, while cochlear dimensions A and B are not well-correlated to each other. Additionally, dimension B is more correlated to duct lengths, the wrapping factor and volume than dimension A. The scala tympani size varies considerably among the population, with the size generally decreasing along insertion depth with dimensional jumps through the trajectory. The mean scala tympani radius was 0.32 mm near the 720° insertion angle. Inter-individual variability was four times that of intra-individual variation. On average, the dimensions of both ears are similar. However, statistically significant differences in clinical dimensions were observed between ears of the same patient, suggesting that size and shape are not the same. Harnessing deep learning-based, automated image analysis tools, our results yielded important insights into cochlear morphology and implant development, helping to reduce insertion trauma and preserving residual hearing.

Investigation of a new electrode array technology for a central auditory prosthesis.

Ongoing clinical studies on patients recently implanted with the auditory midbrain implant (AMI) into the inferior colliculus (IC) for hearing restoration have shown that these patients do not achieve performance levels comparable to cochlear implant patients. The AMI consists of a single-shank array (20 electrodes) for stimulation along the tonotopic axis of the IC. Recent findings suggest that one major limitation in AMI performance is the inability to sufficiently activate neurons across the three-dimensional (3-D) IC. Unfortunately, there are no currently available 3-D array technologies that can be used for clinical applications. More recently, there has been a new initiative by the European Commission to fund and develop 3-D chronic electrode arrays for science and clinical applications through the NeuroProbes project that can overcome the bulkiness and limited 3-D configurations of currently available array technologies. As part of the NeuroProbes initiative, we investigated whether their new array technology could be potentially used for future AMI patients. Since the NeuroProbes technology had not yet been tested for electrical stimulation in an in vivo animal preparation, we performed experiments in ketamine-anesthetized guinea pigs in which we inserted and stimulated a NeuroProbes array within the IC and recorded the corresponding neural activation within the auditory cortex. We used 2-D arrays for this initial feasibility study since they were already available and were sufficient to access the IC and also demonstrate effective activation of the central auditory system. Based on these encouraging results and the ability to develop customized 3-D arrays with the NeuroProbes technology, we can further investigate different stimulation patterns across the ICC to improve AMI performance.

Coactivation of different neurons within an isofrequency lamina of the inferior colliculus elicits enhanced auditory cortical activation.

The phenomenal success of the cochlear implant (CI) is attributed to its ability to provide sufficient temporal and spectral cues for speech understanding. Unfortunately, the CI is ineffective for those without a functional auditory nerve or an implantable cochlea required for CI implementation. As an alternative, our group developed and implanted in deaf patients a new auditory midbrain implant (AMI) to stimulate the central nucleus of the inferior colliculus (ICC). Although the AMI can provide frequency cues, it appears to insufficiently transmit temporal cues for speech understanding. The three-dimensional ICC consists of two-dimensional isofrequency laminae. The single-shank AMI only stimulates one site in any given ICC lamina and does not exhibit enhanced activity (i.e., louder percepts or lower thresholds) for repeated pulses on the same site with intervals <2-5 ms, as occurs for CI pulse or acoustic click stimulation. This enhanced activation, related to short-term temporal integration, is important for tracking the rapid temporal fluctuations of a speech signal. Therefore, we investigated the effects of coactivation of different regions within an ICC lamina on primary auditory cortex activity in ketamine-anesthetized guinea pigs. Interestingly, our findings reveal an enhancement mechanism for integrating converging inputs from an ICC lamina on a fast scale (<6-ms window) that is compromised when stimulating just a single ICC location. Coactivation of two ICC regions also reduces the strong and long-term (>100 ms) suppressive effects induced by repeated stimulation of just a single location. Improving AMI performance may require at least two shanks implanted along the tonotopic gradient of the ICC that enables coactivation of multiple regions along an ICC lamina with the appropriate interstimulus delays.

Effects of pulse phase duration and location of stimulation within the inferior colliculus on auditory cortical evoked potentials in a guinea pig model.

The auditory midbrain implant (AMI), which consists of a single shank array designed for stimulation within the central nucleus of the inferior colliculus (ICC), has been developed for deaf patients who cannot benefit from a cochlear implant. Currently, performance levels in clinical trials for the AMI are far from those achieved by the cochlear implant and vary dramatically across patients, in part due to stimulation location effects. As an initial step towards improving the AMI, we investigated how stimulation of different regions along the isofrequency domain of the ICC as well as varying pulse phase durations and levels affected auditory cortical activity in anesthetized guinea pigs. This study was motivated by the need to determine in which region to implant the single shank array within a three-dimensional ICC structure and what stimulus parameters to use in patients. Our findings indicate that complex and unfavorable cortical activation properties are elicited by stimulation of caudal-dorsal ICC regions with the AMI array. Our results also confirm the existence of different functional regions along the isofrequency domain of the ICC (i.e., a caudal-dorsal and a rostral-ventral region), which has been traditionally unclassified. Based on our study as well as previous animal and human AMI findings, we may need to deliver more complex stimuli than currently used in the AMI patients to effectively activate the caudal ICC or ensure that the single shank AMI is only implanted into a rostral-ventral ICC region in future patients.

Changes in extracellular pH affect glycine receptor channels expressed in HEK 293 cells.

Glycine receptors are expressed throughout the central nervous system working for inhibitory neurotransmission. Since fluctuations of the blood pH value occur under certain physiological and pathological conditions, we investigated the influence of the extracellular pH on glycine homomeric and heteromeric receptor functions using patch clamp in combination with the fast agonist application technique. Our results demonstrated that both alpha1 homomeric and alpha 1 beta heteromeric glycine receptors were remarkably inhibited under acidic extracellular pH. Under alkaline extracellular pH 8.5, there was also a negative functional effect. Desensitization was accelerated depending on pH and a rebound current was observed at an extremely acidic pH value. In double-pulse experiments on alpha1 homomeric receptors, a more rapid recovery of the glycinergic current was shown at pH 4.5 compared to current induced at a physiological pH of 7.2. Our study provided a potential cause for the impaired function of the glycine receptor channels during pH fluctuations occurring in the central nervous system, especially under pathological conditions such as epileptic seizure or ischaemia.