ObjectiveTo investigate the potential to reduce the cochlear dose with robotic photon radiosurgery or intensity-modulated proton therapy planning for vestibular schwannomas.Materials and... Show moreObjectiveTo investigate the potential to reduce the cochlear dose with robotic photon radiosurgery or intensity-modulated proton therapy planning for vestibular schwannomas.Materials and MethodsClinically delivered photon radiosurgery treatment plans were compared to five cochlear-optimized plans: one photon and four proton plans (total of 120). A 1x12 Gy dose was prescribed. Photon plans were generated with Precision (Cyberknife, Accuray) with no PTV margin for set-up errors. Proton plans were generated using an in-house automated multi-criterial planning system with three or nine-beam arrangements, and applying 0 or 3 mm robustness for set-up errors during plan optimization and evaluation (and 3 % range robustness). The sample size was calculated based on a reduction of cochlear Dmean > 1.5 Gy(RBE) from the clinical plans, and resulted in 24 patients.ResultsCompared to the clinical photon plans, a reduction of cochlear Dmean > 1.5 Gy(RBE) could be achieved in 11/24 cochlear-optimized photon plans, 4/24 and 6/24 cochlear-optimized proton plans without set-up robustness for three and nine-beam arrangement, respectively, and in 0/24 proton plans with set-up robustness. The cochlea could best be spared in cases with a distance between tumor and cochlea. Using nine proton beams resulted in a reduced dose to most organs at risk.ConclusionCochlear dose reduction is possible in vestibular schwannoma radiosurgery while maintaining tumor coverage, especially when the tumor is not adjacent to the cochlea. With current set-up robustness, proton therapy is capable of providing lower dose to organs at risk located distant to the tumor, but not for organs adjacent to it. Consequently, photon plans provided better cochlear sparing than proton plans. Show less
In this thesis cochlear morphology and the intra-cochlear position of cochlear implant electrode arrays is being studied. Gaining insight in the variance of cochlear morphology allows to study the... Show moreIn this thesis cochlear morphology and the intra-cochlear position of cochlear implant electrode arrays is being studied. Gaining insight in the variance of cochlear morphology allows to study the effect of morphological characteristics on surgical and speech perception outcomes following cochlear implantation. Furthermore, evaluating the intra-cochlear position of cochlear implant electrode arrays contributes to the search for the optimal position of the array in terms of speech perception outcomes. Show less
Cochlear implants (CI) are implantable devices to rehabilitate hearing for people with severe to profound hearing loss. Over recent years, introduction of new designs have not lead to significant... Show moreCochlear implants (CI) are implantable devices to rehabilitate hearing for people with severe to profound hearing loss. Over recent years, introduction of new designs have not lead to significant improvements in outcomes. Tests to evaluate new sound coding strategies and recording methods are time-consuming, and yield results that are difficult to interpret due to a relatively low number of patients and a large heterogeneity in etiology. As an alternative approach to test new designs, a computational model can be used. In this thesis two computational models are presented and validated for simulation of peripheral responses in cochlear implant users. One model simulates spike times in response to electrical pulse trains. In this model, a three-dimensional volume conduction of the cochlea and an active nerve model were extended with stochasticity, adaptation, and accommodation. It can be used to simulate single fiber action potentials (SFAP) and evoked compound action potentials (ECAP). The second model simulates electrocochleography (eCochG) potentials as recorded intracochlearly. Both models can be used to test developments in sound coding and new recording methods. Furthermore, it can be tested how differences in the individuals’ auditory peripheral system contributes to differences in objective recordings obtained from the individuals. Show less
Heutink, F.; Koch, V.; Verbist, B.; Woude, W.J. van der; Mylanus, E.; Huinck, W.; ... ; Caballo, M. 2020
Background and objective: Performing patient-specific, pre-operative cochlea CT-based measurements could be helpful to positively affect the outcome of cochlear surgery in terms of intracochlear... Show moreBackground and objective: Performing patient-specific, pre-operative cochlea CT-based measurements could be helpful to positively affect the outcome of cochlear surgery in terms of intracochlear trauma and loss of residual hearing. Therefore, we propose a method to automatically segment and measure the human cochlea in clinical ultra-high-resolution (UHR) CT images, and investigate differences in cochlea size for personalized implant planning.Methods: 123 temporal bone CT scans were acquired with two UHR-CT scanners, and used to develop and validate a deep learning-based system for automated cochlea segmentation and measurement. The segmentation algorithm is composed of two major steps (detection and pixel-wise classification) in cascade, and aims at combining the results of a multi-scale computer-aided detection scheme with a U-Net-like architecture for pixelwise classification. The segmentation results were used as an input to the measurement algorithm, which provides automatic cochlear measurements (volume, basal diameter, and cochlear duct length (CDL)) through the combined use of convolutional neural networks and thinning algorithms. Automatic segmentation was validated against manual annotation, by the means of Dice similarity, Boundary-F1 (BF) score, and maximum and average Hausdorff distances, while measurement errors were calculated between the automatic results and the corresponding manually obtained ground truth on a per-patient basis. Finally, the developed system was used to investigate the differences in cochlea size within our patient cohort, to relate the measurement errors to the actual variation in cochlear size across different patients.Results: Automatic segmentation resulted in a Dice of 0.90 +/- 0.03, BF score of 0.95 +/- 0.03, and maximum and average Hausdorff distance of 3.05 +/- 0.39 and 0.32 +/- 0.07 against manual annotation. Automatic cochlear measurements resulted in errors of 8.4% (volume), 5.5% (CDL), 7.8% (basal diameter). The cochlea size varied broadly, ranging between 0.10 and 0.28 ml (volume), 1.3 and 2.5 mm (basal diameter), and 27.7 and 40.1 mm (CDL).Conclusions: The proposed algorithm could successfully segment and analyze the cochlea on UHR-CT images, resulting in accurate measurements of cochlear anatomy. Given the wide variation in cochlear size found in our patient cohort, it may find application as a pre-operative tool in cochlear implant surgery, potentially helping elaborate personalized treatment strategies based on patient-specific, image-based anatomical measurements. (C) 2020 Elsevier B.V. All rights reserved. Show less
The aim of this thesis was to investigate the feasibility of multimodal visualization techniques to observe adult stem cells, in particular HFBSCs, in the living animal. Due to the novelty of... Show moreThe aim of this thesis was to investigate the feasibility of multimodal visualization techniques to observe adult stem cells, in particular HFBSCs, in the living animal. Due to the novelty of HFBSCs in the field of inner ear research, a series of proof-of-principle experiments have been undertaken to investigate if these cells can undergo neuronal differentiation, tolerate genetic modification with lentiviral constructs containing the genes coding for reporter proteins, and tolerate subsequent loading with nanoparticles in vitro. In addition, it was of importance to examine if HFBSCs do integrate into modiolar tissue and if they can be visualized in the cochlea of the guinea pig. Lastly, we performed in vivo studies to investigate the ototoxic effect of ouabain in guinea pigs and the behavior of HFBSCs in mice with traumatic brain injury. Show less
The embryonic development of the human cochlea (the organ of hearing) has been investigated for over one hundred years. However, little is still known about the development on a cellular and... Show moreThe embryonic development of the human cochlea (the organ of hearing) has been investigated for over one hundred years. However, little is still known about the development on a cellular and protein level, which is important to better understand etiologies and pathologies of various types of sensorineural hearing loss. Knowledge of the normal gene expression patterns and cell fate specification in the human cochlea has therefore the potential to aid in the development of gene and cell-based therapeutic strategies. For this reason, we acquired a series of human fetal cochlea of different stages of gestation and investigated several aspects of the normal development of the human cochlea such as the hair cells, the spiral ganglion neurons and the stria vascularis. Also, we investigated the neural crest stem cells residing in the hair follicle bulge. We showed that a protein (TUBB3) often used in immunochemistry to detect a neuron is also expressed both in skin and hair follicle melanocytes in humans meaning that the proposed neural crest stem cell residing in the hair follicle bulge might need revision. Show less
Theunissen, E.A.R.; Zuur, C.L.; Yurda, M.L.; Baan, S. van der; Kornman, A.F.; Boer, J.P. de; ... ; Dreschler, W.A. 2014
Background: Radiation to the inner ear may lead to (irreversible) sensorineural hearing loss. The purpose of this study was to evaluate the long-term effect of radiotherapy on hearing in patients... Show moreBackground: Radiation to the inner ear may lead to (irreversible) sensorineural hearing loss. The purpose of this study was to evaluate the long-term effect of radiotherapy on hearing in patients treated with Intensity Modulated Radiation Therapy (IMRT), sparing the inner ear from high radiation dose as much as possible.Methods: Between 2003 and 2006, 101 patients with head and neck cancer were treated with IMRT. Audiometry was performed before, short-term, and long-term after treatment. Data were compared to normal hearing levels according to the International Organisation for Standardization (ISO). Statistical analysis was done using repeated measurements. None of the patients received chemotherapy.Results: In 36 patients an audiogram at long-term follow-up (median 7.6 years) was available. The mean dose to the cochlea was 17.8 Gy (1.0 66.6 Gy). A hearing deterioration of 1.8 dB at Pure Tone Average (PTA) 0.5 1 2 kHz (p = 0.11), 2.3 dB at PTA 1-2-4 kHz (p = 0.02), and 4.4 dB at PTA 8-10-12.5 kHz (p = 0.01) was found. According to the ISO, the expected age-related hearing loss was 2.7, 4.8, and 8.8 dB at PTA 0.5-1-2 kHz, 1-2-4 kHz, and 8-10-12.5 kHz, respectively.Conclusions: After IMRT with radiation dose constraint to the cochlea, potential long-term adverse effects of IMRT remained subclinical. The progressive hearing loss over time was mild and could be attributed to the natural effects of ageing. Therefore, we recommend that a dose constraint to the cochlea should be incorporated in the head and neck radiotherapy protocols. Show less
