@phdthesis{Rak2009, author = {Rak, Kristen Johannes}, title = {Der Effekt von HDAC Inhibitoren auf neuronale und nicht-neuronale Zellen eines Mausmodells der spinalen Muskelatrophie (SMA)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51516}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {Die Spinale Muskelatrophie (SMA) ist mit einer Inzidenz von 1:6000 die zweith{\"a}ufigste autosomal-rezessive Erbkrankheit im fr{\"u}hen Kindesalter. Die durch den Verlust des SMN- (survival of motoneuron) Gens reduzierte SMN Protein Expression f{\"u}hrt zu einer Degeneration der spinalen Motoneurone mit proximal betonter Muskelschw{\"a}che. Deshalb zielen erste Therapieversuche darauf ab, diese zu erh{\"o}hen. Es war gezeigt worden, dass durch den Einsatz von Histon Deacetylase Inhibitoren (HDAC) in neuronalen Kontroll Zellen und in nicht neuronalen Zellen von SMA Patienten die SMN Protein Expression signifikant gesteigert werden konnte. In der vorgelegten Arbeit wurde untersucht, ob die HDAC Inhibitoren Valproat, SAHA und FK228 Einfluss auf die SMN Protein Expression in kortikalen neuronalen Vorl{\"a}uferzellen (NSC), auf prim{\"a}r embryonale Fibroblasten (PMEF) und auf die morphologischen Ver{\"a}nderungen in prim{\"a}r kultivierten embryonalen Motoneuronen eines Mausmodells der SMA haben. Es konnte eine signifikante Steigerung der SMN Protein Expression durch den Einsatz von Valproat und FK228 in kortikalen neuronalen Vorl{\"a}uferzellen nachgewiesen werden. Es ergab sich jedoch kein Einfluss auf die SMN Protein Expression in prim{\"a}r embryonalen Fibroblasten. Bei NSCs und prim{\"a}r kultivierten embryonalen Motoneuronen wirkten die HDAC Inhibitoren Valproat und FK228 konzentrationsabh{\"a}ngig toxisch auf das {\"U}berleben, die L{\"a}nge der Axone und die Gr{\"o}ße der Wachstumskegel. Es konnte kein positiver Einfluss auf die morphologischen Ver{\"a}nderungen des Mausmodells gesehen werden. Zusammenfassend zeigte sich in der vorgelegten Arbeit ein positiver Effekt auf die SMN Protein Expression durch den Einsatz von HDAC Inhibitoren, der jedoch mit einem toxischen Effekt auf die behandelten neuronalen Zellen einherging.}, subject = {Spinale Muskelatrophie}, language = {de} } @article{HerrmannMuellerGraffKaulitzetal.2022, author = {Herrmann, David P. and M{\"u}ller-Graff, Franz-Tassilo and Kaulitz, Stefan and Cebulla, Mario and Kurz, Anja and Hagen, Rudolf and Neun, Tilmann and Rak, Kristen}, title = {Application of intentional facial nerve stimulation during cochlear implantation as an electrophysiological tool to estimate the intracochlear electrode position}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-17732-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300197}, year = {2022}, abstract = {This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT\(_{SECO}\)). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion.}, language = {en} } @article{RakVoelkerTaegeretal.2019, author = {Rak, Kristen and V{\"o}lker, Johannes and Taeger, Johannes and Bahmer, Andreas and Hagen, Rudolf and Albrecht, Urs-Vito}, title = {Medizinische Apps in der HNO-Heilkunde}, series = {Laryngorhinootologie}, volume = {98}, journal = {Laryngorhinootologie}, number = {S 01}, doi = {10.1055/a-0740-4866}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224948}, pages = {S253-S289}, year = {2019}, abstract = {The implementation of mobile information and communication technology in the field of health services, e.g. in the form of apps, is becoming increasingly important. Unfortunately, the necessary quality criteria are often mising. Thus, it seems important, that in addition to an app controlling authority highly qualified health care professionals participate in the development of these applications. For reasons of liability, however, the physician must exercise great caution in the selection and recommendation of medical apps, especially considering, that only a few apps are certified as medical devices. There are a large number of medical apps on the market, with only a small proportion being assigned to the field of otorhinolaryngology. The areas of audiology, sleep medicine and allergology are most frequently represented. Althouhgh there is increasing scientific work on this topic in the field of otorhinolaryngology, there is a lack of scientific evidence of contents and results, as is generally the case of medical apps. However, there are other possibilities for users to rate medical apps regarding defined qualitiy criteria such as functionality, scientific integrity, but also data privacy. None of the apps assessed by such a evaluation tool met all the required quality criteria, but the applied instrument helped to better assess the application. However, it was possible to consider the quality criteria in the developmental process of an medical app for the field of otorhinolaryngoglogy. In summary, the present work provide a comprehensive insight into the topic "Apps in Otorhinolaryngology" with the aim to use these modern aids in a beneficial way.}, language = {de} } @article{BieniussaKahramanSkornickaetal.2022, author = {Bieniussa, Linda and Kahraman, Baran and Skornicka, Johannes and Schulte, Annemarie and Voelker, Johannes and Jablonka, Sibylle and Hagen, Rudolf and Rak, Kristen}, title = {Pegylated insulin-like growth factor 1 attenuates hair cell loss and promotes presynaptic maintenance of medial olivocochlear cholinergic fibers in the cochlea of the progressive motor neuropathy mouse}, series = {Frontiers in Neurology}, volume = {13}, journal = {Frontiers in Neurology}, issn = {1664-2295}, doi = {10.3389/fneur.2022.885026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276669}, year = {2022}, abstract = {The progressive motor neuropathy (PMN) mouse is a model of an inherited motor neuropathy disease with progressive neurodegeneration. Axon degeneration associates with homozygous mutations of the TBCE gene encoding the tubulin chaperone E protein. TBCE is responsible for the correct dimerization of alpha and beta-tubulin. Strikingly, the PMN mouse also develops a progressive hearing loss after normal hearing onset, characterized by degeneration of the auditory nerve and outer hair cell (OHC) loss. However, the development of this neuronal and cochlear pathology is not fully understood yet. Previous studies with pegylated insulin-like growth factor 1 (peg-IGF-1) treatment in this mouse model have been shown to expand lifespan, weight, muscle strength, and motor coordination. Accordingly, peg-IGF-1 was evaluated for an otoprotective effect. We investigated the effect of peg-IGF-1 on the auditory system by treatment starting at postnatal day 15 (p15). Histological analysis revealed positive effects on OHC synapses of medial olivocochlear (MOC) neuronal fibers and a short-term attenuation of OHC loss. Peg-IGF-1 was able to conditionally restore the disorganization of OHC synapses and maintain the provision of cholinergic acetyltransferase in presynapses. To assess auditory function, frequency-specific auditory brainstem responses and distortion product otoacoustic emissions were recorded in animals on p21 and p28. However, despite the positive effect on MOC fibers and OHC, no restoration of hearing could be achieved. The present work demonstrates that the synaptic pathology of efferent MOC fibers in PMN mice represents a particular form of "efferent auditory neuropathy." Peg-IGF-1 showed an otoprotective effect by preventing the degeneration of OHCs and efferent synapses. However, enhanced efforts are needed to optimize the treatment to obtain detectable improvements in hearing performances.}, language = {en} } @article{NoyaletIlgenBuerkleinetal.2022, author = {Noyalet, Laurent and Ilgen, Lukas and B{\"u}rklein, Miriam and Shehata-Dieler, Wafaa and Taeger, Johannes and Hagen, Rudolf and Neun, Tilmann and Zabler, Simon and Althoff, Daniel and Rak, Kristen}, title = {Vestibular aqueduct morphology and Meniere's disease - development of the vestibular aqueduct score by 3D analysis}, series = {Frontiers in Surgery}, volume = {9}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2022.747517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312893}, year = {2022}, abstract = {Improved radiological examinations with newly developed 3D models may increase understanding of Meniere's disease (MD). The morphology and course of the vestibular aqueduct (VA) in the temporal bone might be related to the severity of MD. The presented study explored, if the VA of MD and non-MD patients can be grouped relative to its angle to the semicircular canals (SCC) and length using a 3D model. Scans of temporal bone specimens (TBS) were performed using micro-CT and micro flat panel volume computed tomography (mfpVCT). Furthermore, scans were carried out in patients and TBS by computed tomography (CT). The angle between the VA and the three SCC, as well as the length of the VA were measured. From these data, a 3D model was constructed to develop the vestibular aqueduct score (VAS). Using different imaging modalities it was demonstrated that angle measurements of the VA are reliable and can be effectively used for detailed diagnostic investigation. To test the clinical relevance, the VAS was applied on MD and on non-MD patients. Length and angle values from MD patients differed from non-MD patients. In MD patients, significantly higher numbers of VAs could be assigned to a distinct group of the VAS. In addition, it was tested, whether the outcome of a treatment option for MD can be correlated to the VAS.}, language = {en} } @article{MuellerGraffIlgenSchendzielorzetal.2022, author = {M{\"u}ller-Graff, Franz-Tassilo and Ilgen, Lukas and Schendzielorz, Philipp and Voelker, Johannes and Taeger, Johannes and Kurz, Anja and Hagen, Rudolf and Neun, Tilmann and Rak, Kristen}, title = {Implementation of secondary reconstructions of flat-panel volume computed tomography (fpVCT) and otological planning software for anatomically based cochlear implantation}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {5}, issn = {1434-4726}, doi = {10.1007/s00405-021-06924-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266798}, pages = {2309-2319}, year = {2022}, abstract = {Purpose For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCT\(_{SECO}\)) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based cochlear implantation. Methods Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCT\(_{SECO}\)) of patients with and without implanted electrodes. Results Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCT\(_{SECO}\) with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCT\(_{SECO}\) compared to MSCT. Conclusion The combination of fpVCT\(_{SECO}\) and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.}, language = {en} } @article{TaegerMuellerGraffLukasetal.2021, author = {Taeger, Johannes and M{\"u}ller-Graff, Franz-Tassilo and Lukas, Ilgen and Schendzielorz, Philipp and Hagen, Rudolf and Neun, Tilman and Rak, Kristen}, title = {Cochlear duct length measurements in computed tomography and magnetic resonance imaging using newly developed techniques}, series = {OTO Open}, volume = {5}, journal = {OTO Open}, number = {3}, doi = {10.1177/2473974X211045312}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-263922}, pages = {1-8}, year = {2021}, abstract = {Objective Growing interest in measuring the cochlear duct length (CDL) has emerged, since it can influence the selection of cochlear implant electrodes. Currently the measurements are performed with ionized radiation imaging. Only a few studies have explored CDL measurements in magnetic resonance imaging (MRI). Therefore, the presented study aims to fill this gap by estimating CDL in MRI and comparing it with multislice computed tomography (CT). Study Design Retrospective data analyses of 42 cochleae. Setting Tertiary care medical center. Methods Diameter (A value) and width (B value) of the cochlea were measured in HOROS software. The CDL and the 2-turn length were determined by the elliptic circular approximation (ECA). In addition, the CDL, the 2-turn length, and the angular length were determined via HOROS software by the multiplanar reconstruction (MPR) method. Results CDL values were significantly shorter in MRI by MPR (d = 1.38 mm, P < .001) but not by ECA. Similar 2-turn length measurements were significantly lower in MRI by MPR (d = 1.67 mm) and ECA (d = 1.19 mm, both P < .001). In contrast, angular length was significantly higher in MRI (d = 26.79°, P < .001). When the values were set in relation to the frequencies of the cochlea, no clinically relevant differences were estimated (58 Hz at 28-mm CDL). Conclusion In the presented study, CDL was investigated in CT and MRI by using different approaches. Since no clinically relevant differences were found, diagnostics with radiation may be omitted prior to cochlear implantation; thus, a concept of radiation-free cochlear implantation could be established.}, language = {en} } @article{TaegerMuellerGraffNeunetal.2021, author = {Taeger, Johannes and M{\"u}ller-Graff, Franz-Tassilo and Neun, Tilmann and K{\"o}ping, Maria and Schendzielorz, Philipp and Hagen, Rudolf and Rak, Kristen}, title = {Highly precise navigation at the lateral skull base by the combination of flat-panel volume CT and electromagnetic navigation}, series = {Science Progress}, volume = {104}, journal = {Science Progress}, number = {3}, issn = {2047-7163}, doi = {10.1177/00368504211032090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250268}, year = {2021}, abstract = {This study aimed to evaluate the feasibility and accuracy of electromagnetic navigation at the lateral skull base in combination with flat panel volume computed tomography (fpVCT) datasets. A mastoidectomy and a posterior tympanotomy were performed on 10 samples of fresh frozen temporal bones. For registration, four self-drilling titanium screws were applied as fiducial markers. Multi-slice computed tomography (MSCT; 600 µm), conventional flat panel volume computed tomography (fpVCT; 466 µm), micro-fpVCT (197 µm) and secondary reconstructed fpVCT (100 µM) scans were performed and data were loaded into the navigation system. The resulting fiducial registration error (FRE) was analysed, and control of the navigation accuracy was performed. The registration process was very quick and reliable with the screws as fiducials. Compared to using the MSCT data, the micro-fpVCT data led to significantly lower FRE values, whereas conventional fpVCT and secondary reconstructed fpVCT data had no advantage in terms of accuracy. For all imaging modalities, there was no relevant visual deviation when targeting defined anatomical points with a navigation probe. fpVCT data are very well suited for electromagnetic navigation at the lateral skull base. The use of titanium screws as fiducial markers turned out to be ideal for comparing different imaging methods. A further evaluation of this approach by a clinical trial is required.}, language = {en} } @article{KoepingShehataDielerCebullaetal.2017, author = {K{\"o}ping, Maria and Shehata-Dieler, Wafaa and Cebulla, Mario and Rak, Kristen and Oder, Daniel and M{\"u}ntze, Jonas and Nordbeck, Peter and Wanner, Christoph and Hagen, Rudolf and Schraven, Sebastian}, title = {Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0188103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169961}, pages = {e0188103}, year = {2017}, abstract = {Background Fabry disease (FD) is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3) in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature. Objective To examine hearing loss in patients with FD depending on cardiac and renal function. Material and methods Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of W{\"u}rzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA\(_{6}\) (0.5, 1, 2, 4, 6, 8) and HF-PTA (6, 8 kHz). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results Sensorineural hearing loss was detected in 58.8\% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2\%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05). Conclusions High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.}, language = {en} } @article{VoelkerVoelkerEngertetal.2021, author = {Voelker, Johannes and Voelker, Christine and Engert, Jonas and Goemann, Nikolas and Hagen, Rudolf and Rak, Kristen}, title = {Spontaneous Calcium Oscillations through Differentiation: A Calcium Imaging Analysis of Rat Cochlear Nucleus Neural Stem Cells}, series = {Cells}, volume = {10}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells10102802}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248482}, year = {2021}, abstract = {Causal therapies for the auditory-pathway and inner-ear diseases are still not yet available for clinical application. Regenerative medicine approaches are discussed and examined as possible therapy options. Neural stem cells could play a role in the regeneration of the auditory pathway. In recent years, neural stem and progenitor cells have been identified in the cochlear nucleus, the second nucleus of the auditory pathway. The current investigation aimed to analyze cell maturation concerning cellular calcium activity. Cochlear nuclei from PND9 CD rats were microscopically dissected and propagated as neurospheres in free-floating cultures in stem-cell medium (Neurobasal, B27, GlutaMAX, EGF, bFGF). After 30 days, the dissociation and plating of these cells took place under withdrawal of the growth factors and the addition of retinoic acid, which induces neural cell differentiation. Calcium imaging analysis with BAPTA-1/Oregon Green was carried out at different times during the differentiation phase. In addition, the influence of different voltage-dependent calcium channels was analyzed through the targeted application of inhibitors of the L-, N-, R- and T-type calcium channels. For this purpose, comparative examinations were performed on CN NSCs, and primary CN neurons. As the cells differentiated, a significant increase in spontaneous neuronal calcium activity was demonstrated. In the differentiation stage, specific frequencies of the spontaneous calcium oscillations were measured in different regions of the individual cells. Initially, the highest frequency of spontaneous calcium oscillations was ascertainable in the maturing somata. Over time, these were overtaken by calcium oscillations in the axons and dendrites. Additionally, in the area of the growth cones, an increasing activity was determined. By inhibiting voltage-dependent calcium channels, their expression and function in the differentiation process were confirmed. A comparable pattern of maturation of these channels was found in CN NSCs and primary CN neurons. The present results show that neural stem cells of the rat cochlear nucleus differentiated not only morphologically but also functionally. Spontaneous calcium activities are of great relevance in terms of neurogenesis and integration into existing neuronal structures. These functional aspects of neurogenesis within the auditory pathway could serve as future targets for the exogenous control of neuronal regeneration.}, language = {en} } @article{EngertRakBieniussaetal.2021, author = {Engert, Jonas and Rak, Kristen and Bieniussa, Linsa and Scholl, Miriam and Hagen, Rudolf and V{\"o}lker, Johannes}, title = {Evaluation of the Neurogenic Potential in the Rat Inferior Colliculus from Early Postnatal Days Until Adulthood}, series = {Molecular Neurobiology}, volume = {58}, journal = {Molecular Neurobiology}, issn = {0893-7648}, doi = {10.1007/s12035-020-02151-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235811}, pages = {719-734}, year = {2021}, abstract = {Neural stem cells (NSCs) have been recently identified in the inferior colliculus (IC). These cells are of particular interest, as no casual therapeutic options for impaired neural structures exist. This research project aims to evaluate the neurogenic potential in the rat IC from early postnatal days until adulthood. The IC of rats from postnatal day 6 up to 48 was examined by neurosphere assays and histological sections. In free-floating IC cell cultures, neurospheres formed from animals from early postnatal to adulthood. The amount of generated neurospheres decreased in older ages and increased with the number of cell line passages. Cells in the neurospheres and the histological sections stained positively with NSC markers (Doublecortin, Sox-2, Musashi-1, Nestin, and Atoh1). Dissociated single cells from the neurospheres differentiated and were stained positively for the neural lineage markers β-III-tubulin, glial fibrillary acidic protein, and myelin basic protein. In addition, NSC markers (Doublecortin, Sox-2, CDK5R1, and Ascl-1) were investigated by qRT-PCR. In conclusion, a neurogenic potential in the rat IC was detected and evaluated from early postnatal days until adulthood. The identification of NSCs in the rat IC and their age-specific characteristics contribute to a better understanding of the development and the plasticity of the auditory pathway and might be activated for therapeutic use.}, language = {en} } @article{JuergensBieniussaVoelkeretal.2020, author = {Juergens, Lukas and Bieniussa, Linda and Voelker, Johannes and Hagen, Rudolf and Rak, Kristen}, title = {Spatio-temporal distribution of tubulin-binding cofactors and posttranslational modifications of tubulin in the cochlea of mice}, series = {Histochemistry and Cell Biology}, volume = {154}, journal = {Histochemistry and Cell Biology}, issn = {0948-6143}, doi = {10.1007/s00418-020-01905-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234852}, pages = {671-681}, year = {2020}, abstract = {The five tubulin-binding cofactors (TBC) are involved in tubulin synthesis and the formation of microtubules. Their importance is highlighted by various diseases and syndromes caused by dysfunction or mutation of these proteins. Posttranslational modifications (PTMs) of tubulin promote different characteristics, including stability-creating subpopulations of tubulin. Cell- and time-specific distribution of PTMs has only been investigated in the organ of Corti in gerbils. The aim of the presented study was to investigate the cell type-specific and time-specific expression patterns of TBC proteins and PTMs for the first time in murine cochleae over several developmental stages. For this, murine cochleae were investigated at the postnatal (P) age P1, P7 and P14 by immunofluorescence analysis. The investigations revealed several profound interspecies differences in the distribution of PTMs between gerbil and mouse. Furthermore, this is the first study to describe the spatio-temporal distribution of TBCs in any tissue ever showing a volatile pattern of expression. The expression analysis of TBC proteins and PTMs of tubulin reveals that these proteins play a role in the physiological development of the cochlea and might be essential for hearing.}, language = {en} } @article{SprinzlMageleSchoergetal.2023, author = {Sprinzl, Georg Mathias and Magele, Astrid and Schoerg, Philipp and Hagen, Rudolf and Rak, Kristen and Kurz, Anja and Van de Heyning, Paul and Calvino, Miryam and Lassaletta, Luis and Gavil{\´a}n, Javier}, title = {A novel representation of audiological and subjective findings for acoustical, bone conduction and direct drive hearing solutions}, series = {Journal of Personalized Medicine}, volume = {13}, journal = {Journal of Personalized Medicine}, number = {3}, issn = {2075-4426}, doi = {10.3390/jpm13030462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311210}, year = {2023}, abstract = {Background: The benefit of hearing rehabilitation is often measured using audiological tests or subjective questionnaires/interviews. It is important to consider both aspects in order to evaluate the overall benefits. Currently, there is no standardized method for reporting combined audiological and patient reported subjective outcome measures in clinical practice. Therefore, this study focuses on showing the patient's audiological, as well as subjective outcomes in one graph using data from an existing study. Method: The present paper illustrated a graph presenting data on four quadrants with audiological and subjective findings. These quadrants represented speech comprehension in quiet (unaided vs. aided) as WRS\% at 65 dB SPL, speech recognition in noise (unaided vs. aided) as SRT dB SNR, sound field threshold (unaided vs. aided) as PTA\(_4\) in dB HL, wearing time and patient satisfaction questionnaire results. Results: As an example, the HEARRING graph in this paper represented audiological and subjective datasets on a single patient level or a cohort of patients for an active bone conduction hearing implant solution. The graph offered the option to follow the user's performance in time. Conclusion: The HEARRING graph allowed representation of a combination of audiological measures with patient reported outcomes in one single graph, indicating the overall benefit of the intervention. In addition, the correlation and consistency between some results (e.g., aided threshold and aided WRS) can be better visualized. Those users who lacked performance benefits on one or more parameters and called for further insight could be visually identified.}, language = {en} } @article{StebaniBlaimerZableretal.2023, author = {Stebani, Jannik and Blaimer, Martin and Zabler, Simon and Neun, Tilmann and Pelt, Dani{\"e}l M. and Rak, Kristen}, title = {Towards fully automated inner ear analysis with deep-learning-based joint segmentation and landmark detection framework}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-45466-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357411}, year = {2023}, abstract = {Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability.}, language = {en} } @article{EngertSpahnBieniussaetal.2023, author = {Engert, Jonas and Spahn, Bjoern and Bieniussa, Linda and Hagen, Rudolf and Rak, Kristen and Voelker, Johannes}, title = {Neurogenic stem cell niche in the auditory Thalamus: in vitro evidence of neural stem cells in the rat medial geniculate body}, series = {Life}, volume = {13}, journal = {Life}, number = {5}, issn = {2075-1729}, doi = {10.3390/life13051188}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319387}, year = {2023}, abstract = {The medial geniculate body (MGB) is a nucleus of the diencephalon representing a relevant segment of the auditory pathway and is part of the metathalamus. It receives afferent information via the inferior brachium of the inferior colliculus and transmits efferent fibers via acoustic radiations to the auditory cortex. Neural stem cells (NSCs) have been detected in certain areas along the auditory pathway. They are of great importance as the induction of an adult stem cell niche might open a regenerative approach to a causal treatment of hearing disorders. Up to now, the existence of NSCs in the MGB has not been determined. Therefore, this study investigated whether the MGB has a neural stem cell potential. For this purpose, cells were extracted from the MGB of PND 8 Sprague-Dawley rats and cultured in a free-floating cell culture assay, which showed mitotic activity and positive staining for stem cell and progenitor markers. In differentiation assays, the markers β-III-tubulin, GFAP, and MBP demonstrated the capacity of single cells to differentiate into neuronal and glial cells. In conclusion, cells from the MGB exhibited the cardinal features of NSCs: self-renewal, the formation of progenitor cells, and differentiation into all neuronal lineage cells. These findings may contribute to a better understanding of the development of the auditory pathway.}, language = {en} }