Register transitions in an in vivo canine model as a function of intrinsic laryngeal muscle stimulation, fundamental frequency, and sound pressure level.

Phonatory instabilities and involuntary register transitions can occur during singing. However, little is known regarding the mechanisms which govern such transitions. To investigate this phenomenon, we systematically varied laryngeal muscle activation and airflow in an in vivo canine larynx model during phonation. We calculated voice range profiles showing average nerve activations for all combinations of fundamental frequency (F0) and sound pressure level (SPL). Further, we determined closed-quotient (CQ) and minimum-posterior-area (MPA) based on high-speed video recordings. While different combinations of muscle activation favored different combinations of F0 and SPL, in the investigated larynx there was a consistent region of instability at about 400 Hz which essentially precluded phonation. An explanation for this region may be a larynx specific coupling between sound source and subglottal tract or an effect based purely on larynx morphology. Register transitions crossed this region, with different combinations of cricothyroid and thyroarytenoid muscle (TA) activation stabilizing higher or lower neighboring frequencies. Observed patterns in CQ and MPA dependent on TA activation reproduced patterns found in singers in previous work. Lack of control of TA stimulation may result in phonation instabilities, and enhanced control of TA stimulation may help to avoid involuntary register transitions, especially in the singing voice.

Synthetic mucus for an ex vivo phonation setup: Creation, application, and effect on excised porcine larynges.

Laryngeal mucus hydrates and lubricates the deformable tissue of the vocal folds and acts as a boundary layer with the airflow from the lungs. However, the effects of the mucus' viscoelasticity on phonation remain widely unknown and mucus has not yet been established in experimental procedures of voice research. In this study, four synthetic mucus samples were created on the basis of xanthan with focus on physiological frequency-dependent viscoelastic properties, which cover viscosities and elasticities over 2 orders of magnitude. An established ex vivo experimental setup was expanded by a reproducible and controllable application method of synthetic mucus. The application method and the suitability of the synthetic mucus samples were successfully verified by fluorescence evidence on the vocal folds even after oscillation experiments. Subsequently, the impact of mucus viscoelasticity on the oscillatory dynamics of the vocal folds, the subglottal pressure, and acoustic signal was investigated with 24 porcine larynges (2304 datasets). Despite the large differences of viscoelasticity, the phonatory characteristics remained stable with only minor statistically significant differences. Overall, this study increased the level of realism in the experimental setup for replication of the phonatory process enabling further research on pathological mucus and exploration of therapeutic options.

Analysis of vibratory mode changes in symmetric and asymmetric activation of the canine larynx.

Investigations of neuromuscular control of voice production have primarily focused on the roles of muscle activation levels, posture, and stiffness at phonation onset. However, little work has been done investigating the stability of the phonation process in regards to spontaneous changes in vibratory mode of vocal fold oscillation as a function of neuromuscular activation. We evaluated 320 phonatory conditions representing combinations of superior and recurrent laryngeal nerve (SLN and RLN) activations in an in vivo canine model of phonation. At each combination of neuromuscular input, airflow was increased linearly to reach phonation onset and beyond from 300 to 1400 mL/s. High-speed video and acoustic data were recorded during phonation, and spectrograms and glottal-area-based parameters were calculated. Vibratory mode changes were detected based on sudden increases or drops of local fundamental frequency. Mode changes occurred only when SLNs were concurrently stimulated and were more frequent for higher, less asymmetric RLN stimulation. A slight increase in amplitude and cycle length perturbation usually preceded the changes in the vibratory mode. However, no inherent differences between signals with mode changes and signals without were found.

Human Laryngeal Mucus from the Vocal Folds: Rheological Characterization by Particle Tracking Microrheology and Oscillatory Shear Rheology.

Mucus consistency affects voice physiology and is connected to voice disorders. Nevertheless, the rheological characteristics of human laryngeal mucus from the vocal folds remain unknown. Knowledge about mucus viscoelasticity enables fabrication of artificial mucus with natural properties, more realistic ex-vivo experiments and promotes a better understanding and improved treatment of dysphonia with regard to mucus consistency. We studied human laryngeal mucus samples from the vocal folds with two complementary approaches: 19 samples were successfully applied to particle tracking microrheology (PTM) and five additional samples to oscillatory shear rheology (OSR). Mucus was collected by experienced laryngologists from patients together with demographic data. The analysis of the viscoelasticity revealed diversity among the investigated mucus samples according to their rigidity (absolute G' and G″). Moreover some samples revealed throughout solid-like character (G' > G″), whereas some underwent a change from solid-like to liquid-like (G' < G″). This led to a subdivision into three groups. We assume that the reason for the differences is a variation in the hydration level of the mucus, which affects the mucin concentration and network formation factors of the mucin mesh. The demographic data could not be correlated to the differences, except for the smoking behavior. Mucus of predominant liquid-like character was associated with current smokers.

Fluid-structure-acoustic interactions in an ex vivo porcine phonation model.

In the clinic, many diagnostic and therapeutic procedures focus on the oscillation patterns of the vocal folds (VF). Dynamic characteristics of the VFs, such as symmetry, periodicity, and full glottal closure, are considered essential features for healthy phonation. However, the relevance of these individual factors in the complex interaction between the airflow, laryngeal structures, and the resulting acoustics has not yet been quantified. Sustained phonation was induced in nine excised porcine larynges without vocal tract (supraglottal structures had been removed above the ventricular folds). The multimodal setup was designed to simultaneously control and monitor key aspects of phonation in the three essential parts of the larynx. More specifically, measurements will comprise (1) the subglottal pressure signal, (2) high-speed recordings in the glottal plane, and (3) the acoustic signal in the supraglottal region. The automated setup regulates glottal airflow, asymmetric arytenoid adduction, and the pre-phonatory glottal gap. Statistical analysis revealed a beneficial influence of VF periodicity and glottal closure on the signal quality of the subglottal pressure and the supraglottal acoustics, whereas VF symmetry only had a negligible influence. Strong correlations were found between the subglottal and supraglottal signal quality, with significant improvement of the acoustic quality for high levels of periodicity and glottal closure.

2020 International Consensus on First Aid Science With Treatment Recommendations.

This is the summary publication of the International Liaison Committee on Resuscitation's 2020 International Consensus on First Aid Science With Treatment Recommendations. It addresses the most recent published evidence reviewed by the First Aid Task Force science experts. This summary addresses the topics of first aid methods of glucose administration for hypoglycemia; techniques for cooling of exertional hyperthermia and heatstroke; recognition of acute stroke; the use of supplementary oxygen in acute stroke; early or first aid use of aspirin for chest pain; control of life- threatening bleeding through the use of tourniquets, haemostatic dressings, direct pressure, or pressure devices; the use of a compression wrap for closed extremity joint injuries; and temporary storage of an avulsed tooth. Additional summaries of scoping reviews are presented for the use of a recovery position, recognition of a concussion, and 6 other first aid topics. The First Aid Task Force has assessed, discussed, and debated the certainty of evidence on the basis of Grading of Recommendations, Assessment, Development, and Evaluation criteria and present their consensus treatment recommendations with evidence-to-decision highlights and identified priority knowledge gaps for future research. The 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) Science With Treatment Recommendations (CoSTR) is the fourth in a series of annual summary publications from the International Liaison Committee on Resuscitation (ILCOR). This 2020 CoSTR for first aid includes new topics addressed by systematic reviews performed within the past 12 months. It also includes updates of the first aid treatment recommendations published from 2010 through 2019 that are based on additional evidence evaluations and updates. As a result, this 2020 CoSTR for first aid represents the most comprehensive update since 2010.

BAGLS, a multihospital Benchmark for Automatic Glottis Segmentation.

Laryngeal videoendoscopy is one of the main tools in clinical examinations for voice disorders and voice research. Using high-speed videoendoscopy, it is possible to fully capture the vocal fold oscillations, however, processing the recordings typically involves a time-consuming segmentation of the glottal area by trained experts. Even though automatic methods have been proposed and the task is particularly suited for deep learning methods, there are no public datasets and benchmarks available to compare methods and to allow training of generalizing deep learning models. In an international collaboration of researchers from seven institutions from the EU and USA, we have created BAGLS, a large, multihospital dataset of 59,250 high-speed videoendoscopy frames with individually annotated segmentation masks. The frames are based on 640 recordings of healthy and disordered subjects that were recorded with varying technical equipment by numerous clinicians. The BAGLS dataset will allow an objective comparison of glottis segmentation methods and will enable interested researchers to train their own models and compare their methods.

Investigation of phonatory characteristics using ex vivo rabbit larynges.

Quantitative analysis of phonatory characteristics of rabbits has been widely neglected. However, preliminary studies established the rabbit larynx as a potential model of human phonation. This study reports quantitative data on phonation using ex vivo rabbit larynx models to achieve more insight into dependencies of three main components of the phonation process, including airflow, vocal fold dynamics, and the acoustic output. Sustained phonation was induced in 11 ex vivo rabbit larynges. For 414 phonatory conditions, vocal fold vibrations, acoustic, and aerodynamic parameters were analyzed as functions of longitudinal vocal fold pre-stress, applied air flow, and glottal closure insufficiency. Dimensions of the vocal folds were measured and histological data were analyzed. Glottal closure characteristics improved for increasing longitudinal pre-stress and applied airflow. For the subglottal pressure signal only the cepstral peak prominence showed dependency on glottal closure. In contrast, vibrational, acoustic, and aerodynamic parameters were found to be highly dependent on the degree of glottal closure: The more complete the glottal closure during phonation, the better the aerodynamic and acoustic characteristics. Hence, complete or at least partial glottal closure appears to enhance acoustic signal quality. Finally, results validate the ex vivo rabbit larynx as an effective model for analyzing the phonatory process.

Influence of glottal closure on the phonatory process in ex vivo porcine larynges.

Many cases of disturbed voice signals can be attributed to incomplete glottal closure, vocal fold oscillation asymmetries, and aperiodicity. Often these phenomena occur simultaneously and interact with each other, making a systematic, isolated investigation challenging. Therefore, ex vivo porcine experiments were performed which enable direct control of glottal configurations. Different pre-phonatory glottal gap sizes, adduction levels, and flow rates were adjusted. The resulting glottal closure types were identified in a post-processing step. Finally, the acoustic quality, aerodynamic parameters, and the characteristics of vocal fold oscillation were analyzed in reference to the glottal closure types. Results show that complete glottal closure stabilizes the phonation process indicated through a reduced left-right phase asymmetry, increased amplitude and time periodicity, and an increase in the acoustic quality. Although asymmetry and periodicity parameter variation covers only a small range of absolute values, these small variations have a remarkable influence on the acoustic quality. Due to the fact that these parameters cannot be influenced directly, the authors suggest that the (surgical) reduction of the glottal gap seems to be a promising method to stabilize the phonatory process, which has to be confirmed in future studies.

Automated setup for ex vivo larynx experiments.

Ex vivo larynx experiments are limited in time due to degeneration of the laryngeal tissues. In order to acquire a significant and comparable amount of data, automatization of current manual experimental procedures is desirable. A computer controlled, electro-mechanical setup was developed for time-dependent variation of specific physiological parameters, including adduction and elongation level of the vocal folds and glottal flow. The setup offers a standardized method to induce defined forces on the laryngeal cartilages. Furthermore, phonation onset is detected automatically and the subsequent measurement procedure is automated and standardized to improve the efficiency of the experimental process. The setup was validated using four ex vivo porcine larynges, whereas each validation measurement series was executed with one separate larynx. Altogether 31 single measurements were undertaken, which can be summed up to a total experimental time of about 4 min. Vocal fold elongation and adduction lead both to an increase in fundamental frequency and subglottal pressure. Measurement procedures like applying defined subglottal pressure steps and onset-offset detection were reliably executed. The setup allows for a computer-based parameter control, which enables fast experimental execution over a wide range of laryngeal configurations. This maximizes the number of measurements and reduces personal effort compared with manual procedures.

Dynamic vocal fold parameters with changing adduction in ex-vivo hemilarynx experiments.

Ex-vivo hemilarynx experiments allow the visualization and quantification of three-dimensional dynamics of the medial vocal fold surface. For three excised human male larynges, the vibrational output, the glottal flow resistance, and the sound pressure during sustained phonation were analyzed as a function of vocal fold adduction for varying subglottal pressure. Empirical eigenfunctions, displacements, and velocities were investigated along the vocal fold surface. For two larynges, an increase of adduction level resulted in an increase of the glottal flow resistance at equal subglottal pressures. This caused an increase of lateral and vertical oscillation amplitudes and velocity indicating an improved energy transfer from the airflow to the vocal folds. In contrast, the third larynx exhibited an amplitude decrease for rising adduction accompanying reduction of the flow resistance. By evaluating the empirical eigenfunctions, this reduced flow resistance was assigned to an unbalanced oscillation pattern with predominantly lateral amplitudes. The results suggest that adduction facilitates the phonatory process by increasing the glottal flow resistance and enhancing the vibrational amplitudes. However, this interrelation only holds for a maintained balanced ratio between vertical and lateral displacements. Indeed, a balanced vertical-lateral oscillation pattern may be more beneficial to phonation than strong periodicity with predominantly lateral vibrations.

Influence and interactions of laryngeal adductors and cricothyroid muscles on fundamental frequency and glottal posture control.

The interactions of the intrinsic laryngeal muscles (ILMs) in controlling fundamental frequency (F0) and glottal posture remain unclear. In an in vivo canine model, three sets of intrinsic laryngeal muscles-the thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid plus interarytenoid (LCA/IA) muscle complex-were independently and accurately stimulated in a graded manner using distal laryngeal nerve stimulation. Graded neuromuscular stimulation was used to independently activate these paired intrinsic laryngeal muscles over a range from threshold to maximal activation, to produce 320 distinct laryngeal phonatory postures. At phonation onset these activation conditions were evaluated in terms of their vocal fold strain, glottal width at the vocal processes, fundamental frequency (F0), subglottic pressure, and airflow. F0 ranged from 69 to 772 Hz and clustered into chest-like and falsetto-like groups. CT activation was always required to raise F0, but could also lower F0 at low TA and LCA/IA activation levels. Increasing TA activation first increased then decreased F0 in all CT and LCA/IA activation conditions. Increasing TA activation also facilitated production of high F0 at a lower onset pressure. Independent control of membranous (TA) and cartilaginous (LCA/IA) glottal closure enabled multiple pathways for F0 control via changes in glottal posture.

Preliminary results on the influence of engineered artificial mucus layer on phonation.

PURPOSE Previous studies have confirmed the influence of dehydration and an altered mucus (e.g., due to pathologies) on phonation. However, the underlying reasons for these influences are not fully understood. This study was a preliminary inquiry into the influences of mucus architecture and concentration on vocal fold oscillation. METHOD Two excised human larynges were investigated in an in vitro setup. The oscillations of the vocal folds at various airflow volume rates were recorded through the use of high-speed imaging. Engineered mucus containing polymers (interconnected polymers and linear polymers) was applied to the vocal folds. From the high-speed footage, glottal parameters were extracted through the use of objective methods and were compared to a gold standard (physiological saline solution). RESULTS Variations were found for all applications of mucus. Fundamental frequency dropped and the oscillatory behavior (speed quotient [SQ], closing quotient [CQ]) changed for both larynges. The 2 applied mucus architectures displayed different effects on the larynges. The interconnected polymer displayed clear low-pass filter characteristics not found for the linear polymer. Increase of polymer concentration affected parameters to a certain point. CONCLUSION The data confirm results found in previous studies. Furthermore, the different effects-comparing architecture and concentration-suggest that, in the future, synthetic mucus can be designed to improve phonation.

Three-dimensional biomechanical properties of human vocal folds: parameter optimization of a numerical model to match in vitro dynamics.

The human voice signal originates from the vibrations of the two vocal folds within the larynx. The interactions of several intrinsic laryngeal muscles adduct and shape the vocal folds to facilitate vibration in response to airflow. Three-dimensional vocal fold dynamics are extracted from in vitro hemilarynx experiments and fitted by a numerical three-dimensional-multi-mass-model (3DM) using an optimization procedure. In this work, the 3DM dynamics are optimized over 24 experimental data sets to estimate biomechanical vocal fold properties during phonation. Accuracy of the optimization is verified by low normalized error (0.13 ± 0.02), high correlation (83% ± 2%), and reproducible subglottal pressure values. The optimized, 3DM parameters yielded biomechanical variations in tissue properties along the vocal fold surface, including variations in both the local mass and stiffness of vocal folds. That is, both mass and stiffness increased along the superior-to-inferior direction. These variations were statistically analyzed under different experimental conditions (e.g., an increase in tension as a function of vocal fold elongation and an increase in stiffness and a decrease in mass as a function of glottal airflow). The study showed that physiologically relevant vocal fold tissue properties, which cannot be directly measured during in vivo human phonation, can be captured using this 3D-modeling technique.

Neuromuscular control of fundamental frequency and glottal posture at phonation onset.

The laryngeal neuromuscular mechanisms for modulating glottal posture and fundamental frequency are of interest in understanding normal laryngeal physiology and treating vocal pathology. The intrinsic laryngeal muscles in an in vivo canine model were electrically activated in a graded fashion to investigate their effects on onset frequency, phonation onset pressure, vocal fold strain, and glottal distance at the vocal processes. Muscle activation plots for these laryngeal parameters were evaluated for the interaction of following pairs of muscle activation conditions: (1) cricothyroid (CT) versus all laryngeal adductors (TA/LCA/IA), (2) CT versus LCA/IA, (3) CT versus thyroarytenoid (TA) and, (4) TA versus LCA/IA (LCA: lateral cricoarytenoid muscle, IA: interarytenoid). Increases in onset frequency and strain were primarily affected by CT activation. Onset pressure correlated with activation of all adductors in activation condition 1, but primarily with CT activation in conditions 2 and 3. TA and CT were antagonistic for strain. LCA/IA activation primarily closed the cartilaginous glottis while TA activation closed the mid-membranous glottis.

Effects of the epilarynx area on vocal fold dynamics and the primary voice signal.

For the analysis of vocal fold dynamics, sub- and supraglottal influences must be taken into account, as recent studies have shown. In this work, we analyze the influence of changes in the epilaryngeal area on vocal fold dynamics. We investigate two excised female larynges in a hemilarynx setup combined with a synthetic vocal tract consisting of hard plastic and simulating the vowel /a/. Eigenmodes, amplitudes, and velocities of the oscillations, the subglottal pressures (P(sub)), and sound pressure levels (SPLs) of the generated signal are investigated as a function of three distinctive epilaryngeal areas (28.4 mm(2), 71.0 mm(2), and 205.9 mm(2)). The results showed that the SPL is independent of the epilarynx cross section and exhibits a nonlinear relation to the insufflated airflow. The P(sub) decreased with an increase in the epilaryngeal area and displayed linear relations to the airflow. The principal eigenfunctions (EEFs) from the vocal fold dynamics exhibited lateral movement for the first EEF and rotational motion for the second EEF. In total, the first two EEFs covered a minimum of 60% of the energy, with an average of more than 50% for the first EEF. Correlations to the epilarynx areas were not found. Maximal values for amplitudes (up to 2.5 mm) and velocities (up to 1.57 mm/ms) changed with varying epilaryngeal area but did not show consistent behavior for both larynges. We conclude that the size of the epilaryngeal area has significant influence on vocal fold dynamics but does not significantly affect the resultant SPL.

Computation of physiological human vocal fold parameters by mathematical optimization of a biomechanical model.

With the use of an endoscopic, high-speed camera, vocal fold dynamics may be observed clinically during phonation. However, observation and subjective judgment alone may be insufficient for clinical diagnosis and documentation of improved vocal function, especially when the laryngeal disease lacks any clear morphological presentation. In this study, biomechanical parameters of the vocal folds are computed by adjusting the corresponding parameters of a three-dimensional model until the dynamics of both systems are similar. First, a mathematical optimization method is presented. Next, model parameters (such as pressure, tension and masses) are adjusted to reproduce vocal fold dynamics, and the deduced parameters are physiologically interpreted. Various combinations of global and local optimization techniques are attempted. Evaluation of the optimization procedure is performed using 50 synthetically generated data sets. The results show sufficient reliability, including 0.07 normalized error, 96% correlation, and 91% accuracy. The technique is also demonstrated on data from human hemilarynx experiments, in which a low normalized error (0.16) and high correlation (84%) values were achieved. In the future, this technique may be applied to clinical high-speed images, yielding objective measures with which to document improved vocal function of patients with voice disorders.

Material parameter computation for multi-layered vocal fold models.

Today, the prevention and treatment of voice disorders is an ever-increasing health concern. Since many occupations rely on verbal communication, vocal health is necessary just to maintain one's livelihood. Commonly applied models to study vocal fold vibrations and air flow distributions are self sustained physical models of the larynx composed of artificial silicone vocal folds. Choosing appropriate mechanical parameters for these vocal fold models while considering simplifications due to manufacturing restrictions is difficult but crucial for achieving realistic behavior. In the present work, a combination of experimental and numerical approaches to compute material parameters for synthetic vocal fold models is presented. The material parameters are derived from deformation behaviors of excised human larynges. The resulting deformations are used as reference displacements for a tracking functional to be optimized. Material optimization was applied to three-dimensional vocal fold models based on isotropic and transverse-isotropic material laws, considering both a layered model with homogeneous material properties on each layer and an inhomogeneous model. The best results exhibited a transversal-isotropic inhomogeneous (i.e., not producible) model. For the homogeneous model (three layers), the transversal-isotropic material parameters were also computed for each layer yielding deformations similar to the measured human vocal fold deformations.

Experiments on Analysing Voice Production: Excised (Human, Animal) and In Vivo (Animal) Approaches.

Experiments on human and on animal excised specimens as well as in vivo animal preparations are so far the most realistic approaches to simulate the in vivo process of human phonation. These experiments do not have the disadvantage of limited space within the neck and enable studies of the actual organ necessary for phonation, i.e., the larynx. The studies additionally allow the analysis of flow, vocal fold dynamics, and resulting acoustics in relation to well-defined laryngeal alterations. PURPOSE OF REVIEW: This paper provides an overview of the applications and usefulness of excised (human/animal) specimen and in vivo animal experiments in voice research. These experiments have enabled visualization and analysis of dehydration effects, vocal fold scarring, bifurcation and chaotic vibrations, three-dimensional vibrations, aerodynamic effects, and mucosal wave propagation along the medial surface. Quantitative data will be shown to give an overview of measured laryngeal parameter values. As yet, a full understanding of all existing interactions in voice production has not been achieved, and thus, where possible, we try to indicate areas needing further study. RECENT FINDINGS: A further motivation behind this review is to highlight recent findings and technologies related to the study of vocal fold dynamics and its applications. For example, studies of interactions between vocal tract airflow and generation of acoustics have recently shown that airflow superior to the glottis is governed by not only vocal fold dynamics but also by subglottal and supraglottal structures. In addition, promising new methods to investigate kinematics and dynamics have been reported recently, including dynamic optical coherence tomography, X-ray stroboscopy and three-dimensional reconstruction with laser projection systems. Finally, we touch on the relevance of vocal fold dynamics to clinical laryngology and to clinically-oriented research.

Graded activation of the intrinsic laryngeal muscles for vocal fold posturing.

Previous investigations using in vivo models to study the role of intrinsic laryngeal muscles in phonation have used neuromuscular stimulation to study voice parameters. However, these studies used coarse stimulation techniques using limited levels of neuromuscular stimulation. In the current investigation, a technique for fine control of laryngeal posturing was developed using graded stimulation of the laryngeal nerves. Vocal fold strain history to graded stimulation and a methodology for establishing symmetric laryngeal activation is presented. This methodology has immediate applications for the study of laryngeal paralysis and paresis, as well as general questions of neuromuscular control of the larynx.