The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Otorhinolaryngology.
- Research programme: Disorders of the head and neck
- Department: Otorhinolaryngology
- Programme leader: Prof. Dr. P.P.G. van Benthem
- Principal investigators: Prof. Dr. Ir. J.H.M. Frijns, Dr. Ir. J.J. Briaire
- Biomedical research profile: Translational Neuroscience
- Generic research profile: Innovation in Health Strategy and Quality of Care
Aim and focus
The ENT-department envisages societal impact of research, through identification of gaps in knowledge regarding specific categories of patients, i.e., patients suffering from diseases resulting in hearing loss or damage to the vestibular organ. To link clinically relevant gaps in knowledge to wanted research, all modalities of research are used; biotechnological research, biomedical research, translational research, outcome research and healthcare research. To ensure maximum societal impact, integrated strategies of these modalities are used.
The ENT-department focuses on (neuro-)otology (disorders of the inner ear, i.e., the cochlea and vestibular organ), specifically auditory implants (CIs and ABIs, electrical prostheses for the deaf) and vestibular disorders, with a focus on Meniere’s disease. The research on electrical stimulation of the auditory pathways has a long-standing history in the study of the electrode-to-neural interface, aiming at the development of new clinically applicable speech coding strategies and electrode designs focusing on societal impact. Thereby, it has a strong translational character, and combines computational modelling, imaging, electrophysiology (in animals and humans), psychophysics and clinical trials. The group has initiated stem cell research aimed at regenerative medicine of the auditory nerve and, more recently, the vestibular organ.
There are three main research tracks, the first being more technical, the second more biological, and the third one focussing on evaluation of care.
Position in international context
The Leiden CI programme is widely recognized as leading in the field of computational modelling, imaging and translational evaluation of new and evolving stimulation patterns. The computational model forms a discriminative factor for an internationally recognized clinical research and training program. Within the Medical Delta initiative, the group provides clinical, modelling and physiological input to the development of new thin film electrodes and the development of more accurate neural response recording systems in cooperation with a number of groups in TU Delft and Advanced Bionics (one of the major CI manufacturers). Further collaborations include the Leiden Institute for Brain and Cognition (LIBC- Radiology, Linguistics and Psychology), the UMC Nijmegen, the KU Leuven (Belgium), Cambridge University (UK), the University of Sheffield (UK), the University of Washington (Seattle, USA), and the New York University (USA). More recently, we started with a programme on the dizzy patient, with a focus on Meniere’s disease in collaboration with the Apeldoorns Duizeligheidscentrum and the Reinier de Graaf /HAGA groep. In the field of outcome research, we work with the ENT-review group of the Cochrane collaboration, Oxford, UK, the Ear institute of the University college London and the Hospital for Sick Children, Toronto, Canada. For future biomedical/stem cell research, we joined the strategic alliance, RegMedXB, of the LUMC and the Medizinische Hochschule Hannover. Furthermore, alliances in this field exist with the University of Innsbruck, Austria and the University of Uppsala, Sweden.
Content / highlights / achievements
The translational research on CIs and ABIs is embedded and highly integrated in the second-largest Dutch clinical program on auditory prostheses for the deaf and severely hard of hearing. This clinical program is an official TRF (Top Referential Function) of the LUMC.
The CI computer model, which is widely recognized as the most sophisticated in the world, now allows for patient-specific predictions, e.g., by integrating histological with radiological data into a frequency-to-place map. This model combines a detailed electrical volume conduction model of the human cochlea with an active (physiological) neural model. Its predictions in terms of spread of the electrical field and in terms of neural recruitment have been validated against electrical, physiological and clinical measurements in actual CI recipients. Therefore, the model has, e.g., been applied to predict the effect of various positions of existing and conceptual electrodes in the cochlea. In addition, it has been used to get otherwise inaccessible insights in the effects underlying a wide variety of speech coding strategies (e.g., on current steering and current focussing). In recent years, the model has been extended to also include a stochastic (phenomenological) neural model. Now it is also able to predict the neural response to electrical pulse trains, produced by a (digitally emulated) speech processor in response to actual speech stimuli. The model plays a key role in the Leiden research programme, as it is used in the design and evaluation of most pre-clinical and clinical studies.
Together with the department of Neuroradiology we developed an internationally recognized CT-scan protocol for CI’s, published the world’s first paper on 7T imaging of the inner and initiated an international consensus on cochlear coordinates. Based on these achievements the relevance of in vivo imaging for cochlear implantation has been investigated, leading to assistive tools to improve implantation planning. It’s important to develop such new tools to better preserve intracochlear structures (and residual hearing) during cochlear implant-electrode insertion. E.g., as a result of a study on prospective monitoring of electrode placement, using low-dose CT-scans and direct feedback to the surgeon, we were able to induce a five-fold reduction of the number of translocations of the HiFocusMS electrode array from the scala tympani to the scala vestibuli, which is inevitably associated with complete loss of residual hearing (from over 30% to 6% of cases). A next step is the development and validation of an automatic 3D image processing app, providing pre-operative guidance to the surgeon, which will be coupled with a real-time intra-operative monitoring system, based upon electrical and electrophysiological measurements (in part via the implant itself).
Clinical outcome research by our group has led to expanding candidacy indication criteria for cochlear implantation in several ways. For prelingually deafened adult CI-candidates, we were the first to show that the speech perception with CI is largely predicted by the intelligibility of the speech produced by the candidates, and we were able to develop, validate and implement a standard clinical test for candidacy for this group of marginal candidates. A study, performed in collaboration with four other Dutch and Flemish paediatric CI-centres, has largely contributed to the reimbursement of bilateral cochlear implantation in congenitally deaf children, not only in the Netherlands, but also elsewhere (e.g., the USA).
Recently, careful analysis of the pre- and postoperative speech perception outcomes in postlingually deafened adults showed that candidates have a chance of more than 90% to improve in terms of speech understanding with (unilateral) CI over (bilateral) conventional hearing aids, if their speech understanding on a standard Dutch monosyllabic word test is 80% phonemes correct or less. This has, amongst others, led to the nationwide widening of candidacy criteria for cochlear implantation.
Furthermore, we have conducted innovative clinical research, e.g., on speech coding strategies, and objective measures (amongst others, developing novel ways to determine the spread of excitation in CI with electrically evoked compound action potentials of the auditory nerve). In recent years, the department has been involved in research on screening methods for hearing impairment (the DECIBEL study) and socio-emotional development of the hearing impaired. Both studies are now combined in a longitudinal evaluative study of the effects of early detection of hearing impairment and subsequent interventions on the development of children. An important finding of this research line is that deaf children with a cochlear implant show an in many respects normal socio-emotional development and significantly less psychopathology than hard of hearing children with conventional hearing aids.
With the recent arrival of the new chair, prof. dr. P.P.G. van Benthem, the subjects of the inner ear research programme have been extended from the cochlea to include the vestibular organ. Originating from and consisting of similar (neuro)epithelia, the function of both organs is based on comparable (electro)physiological processes, and it will be no surprise that clinical expression of defects in their genetics, anatomy or physiology is seen in both parts of the inner ear, the cochlea and vestibular organ. Elaboration of the programme, using the research modalities and techniques already developed, will be an enrichment of the programme as a whole and reinforce clinical and ultimately, societal relevance.
Together with the Apeldoorns Duizeligheidscentrum, a tertiary dizziness clinic, much work on clinical research with regard to evaluation and validation of new diagnostic tools and treatment modalities has been executed. Also in this field we have an international position, illustrated by the fact that 4 out of 7 Cochrane reviews related to this subject are published by our group.
Examples of societal impact
- The Dutch-Flemish multi-centre study on paediatric bilateral cochlear implantation (Boons et al., 2012) has played a key role in the decision on reimbursement of bilateral CI in children, not only in the Netherlands, but also, in the United States.
- Based on a retrospective analysis of the outcomes in all our post-lingual deaf CI recipients, we have developed more relaxed, evidence-based candidacy criteria for cochlear implantation, which have been accepted nation-wide (Snel-Bongers et al., Ear Hear., in press).
- In consecutive prospective studies, we have developed and validated a test of speech production prior to implantation, which is highly predictive of the postoperative speech perception in pre-lingual deaf adult CI candidates (Van Dijkhuizen et al., Ear Hear. 2011, 2016). The findings are now routinely used in clinical practice.
- The eCAP recording chip, developed in the STW-funded ReaSONS project in collaboration with the Delft University of Technology, is being patented, and will be further developed and evaluated in an STW demonstrator project with several other application areas.
- The clinical merits of the novel algorithm to derive spread of excitation based on deconvolution, also developed in the ReaSONS project (Biesheuvel et al., 2016), are now being evaluated (in several centres and with at least manufacturers).
- We have developed the first test of pitch discrimination with CIs that is highly correlated with speech perception (publication in preparation). It will be implemented as a self-test that patients can do prior to a fitting session with the audiologist.
- The insights we gained on the overall positive and sometimes detrimental value of a CROS hearing aid contralateral to a unilateral cochlear implant (Taal et al., 2016), has led to the addition of a fast switch-on and -off option on the first dedicated device (the Naida CROS by Advanced Bionics) to be used in circumstances where mainly noise rather than speech is coming from the CROS side.
- Together with the Dutch association for patients suffering from Meniere’s disease, insight has been gained on the topics that are relevant for patients to do research on. In addition, we investigated what outcomes are important to patients.
Future themesThe research on the vestibular system will not only lead to more outcome research, but also triggered a biomedical research project called ‘inner ear on-a-chip’. Through biomedical research, using (stem)cell culture techniques, we hope to create the part of the inner ear that is responsible for the production of endolymph fluid, in vitro. Dysfunction of this part is supposedly responsible for the pathophysiological mechanisms leading to the symptoms of patients suffering from Meniere’s disease. Linking this ‘organoid’ to a ‘chip’ will give us the opportunity to measure the effects of relevant pharmacological products on the endolymph production, thereby creating a platform for drug testing. If grown from patients with genetic defects that are known to influence endolymph producing epithelium of the inner ear, the ‘organoid on-a-chip’ can be used for gene therapy. Knowledge gained in this way, will be brought back to clinical outcome research, in concordance with our vision on research, that maximum relevance for patient care will be achieved through integrated use of several modalities of research. Feasibility of this project is high, as our department has already done part or the work on the cochlea and the LUMC has great expertise in regenerative medicine and is leading in organ on-a-chip research.
Summary of future themes in inner ear and vestibular research
- Development, in vitro testing and clinical evaluation of a new minimally traumatic cochlear implant electrode array, incorporating clinical expertise and insights gained from the Leiden computer model of the implanted cochlea, e.g., providing a more physiological tonotopic representation in the cochlea (collaboration with CI-manufacturer Advanced Bionics).
- Development of neural recording electronics and an improved electrode array, with embedded electronics, and possibly also mechanical actuators (collaboration with TU Delft).
- The value of (CT and 7T/functional MRI) imaging in the assessment of CI-performance, cochlear anatomy and insertion trauma (Leiden Institute for Brain and Cognition, LIBC).
- Assessment and optimization of prosody and emotion perception with CI, both in western and in tonal languages (LIBC, Faculty of Social Sciences, Linguistics).
- Emotional development and psychopathology of deaf children with and without a CI (together with Faculty of Social Sciences).
- Optimizing the care for deaf and hard of hearing children (together with Faculty of Social Sciences and the Dutch Foundation for Deaf and Hard of Hearing Children, NSDSK).
- Enhanced neural response recordings of the auditory nerve, including new methods to determine the neural survival status of the auditory nerve
- SMART surgery: Randomized controlled trials in Ear, Nose and Throat surgery and Neurosurgery; Impact on patient value and health care budget in the Netherlands.
- Development and validation of an automatic 3D image processing app, providing pre-operative guidance to the surgeon, which will be coupled with a real-time intra-operative monitoring system for cochlear implantation (including robotics)
- Developmental biology of the cochlea and vestibular organ.
- Development of an Organ-on-a-Chip for the vestibular system
- Transfer of knowledge and expertise to other fields of electrical stimulation and recording in the human neural system (optical prostheses, deep brain stimulation, brain reading and writing etc.) via the NeuroTech-NL initiative.
Cohesion within LUMC
- The research program is embedded in the LUMC profile areas TN (Leiden Centre for Translational Neuroscience) and IHQC (Innovation in Health Strategy Quality of Care).
- Parts of the CI-research are embedded in the LIBC and the Medical Delta-initiative, or are conducted in collaboration with Medical Decision Making, the department of Neuroradiology, Neurophysiology or Pediatrics. The stem cell project has a close collaboration with the department of Molecular Imaging (now in part in Erasmus MC) and a growing collaboration with the department of Anatomy (Developmental Biology). Furthermore, it is part of RegMedXB, in collaboration with the Medizinische Hochschule, Hannover.