Telemedical Concepts for Heart Failure Patients Treated with a Wearable Cardioverter Defibrillator.

Over the last few decades, implantable defibrillators have become an established method of treating malign cardiac arrhythmias. There are some situations, however, in which it would be premature to implant a permanent defibrillator. In such cases, a wearable cardioverter defibrillator (WCD) can provide temporary relief and protect patients from life-threatening cardiac arrhythmias. Treatment with WCD is now included in national and international guidelines. Nevertheless, there are still some deficits in connection with WCD, especially regarding rescue chain optimization. For example, there is currently no telemedical link in place to emergency call centers and healthcare practitioners in the case of an event. Likewise, there are still some problems with rhythm analysis, concerning both shock delivery and cardiopulmonary resuscitation (CPR). These deficits are now to be addressed within the framework of MiniDefi, a project funded by the German Federal Ministry of Education and Research (BMBF). The concepts are described here for the first time.

Tissue-Engineered Vocal Fold Mucosa Implantation in Rabbits.

OBJECTIVE: To assess phonatory function and wound healing of a tissue-engineered vocal fold mucosa (TE-VFM) in rabbits. An "artificial" vocal fold would be valuable for reconstructing refractory scars and resection defects, particularly one that uses readily available autologous cells and scaffold. This work implants a candidate TE-VFM after resecting native epithelium and lamina propria in rabbits. STUDY DESIGN: Prospective animal study. SETTING: Research laboratory. SUBJECTS AND METHODS: Rabbit adipose-derived stem cells were isolated and cultured in three-dimensional fibrin scaffolds to form TE-VFM. Eight rabbits underwent laryngofissure, unilateral European Laryngologic Society type 2 cordectomy, and immediate reconstruction with TE-VFM. After 4 weeks, larynges were excised, phonated, and examined by histology. RESULTS: Uniform TE-VFM implants were created, with rabbit mesenchymal cells populated throughout fibrin hydrogels. Rabbits recovered uneventfully after implantation. Phonation was achieved in all, with mucosal waves evident at the implant site. Histology after 4 weeks showed resorbed fibrin matrix, continuous epithelium, and mildly increased collagen relative to contralateral unoperated vocal folds. Elastic fiber appearance was highly variable. Inflammatory cell infiltrate was limited to animals receiving sex-mismatched implants. CONCLUSION: TE-VFMs were successfully implanted into 8 rabbits, with minor evidence of scar formation and immune reaction. Vibration was preserved 4 weeks after resecting and reconstructing the complete vocal fold cover layer. Further studies will investigate the mechanism and durability of improvement. TE-VFM with autologous cells is a promising new approach for vocal fold reconstruction.

Preliminary Study of the Open Quotient in an Ex Vivo Perfused Human Larynx.

IMPORTANCE: Scientific understanding of human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. To our knowledge, direct experimentation of human voice production has previously not been possible owing to its invasive nature. The feasibility of an ex vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation. OBJECTIVE: To investigate the association between adductor muscle group stimulation and the open quotient (OQ) (the fraction of the cycle during which the glottis remains open) of vocal fold vibration. DESIGN, SETTING, AND PARTICIPANTS: An ex vivo perfused human tissue study was conducted at a physiology laboratory. Human larynx recovered from organ donors within 2 hours of cardiac death was used. The study was performed on May 19, 2014; data analysis took place from June 1, 2014, to December 15, 2014. INTERVENTIONS: Perfusion with donated human blood was reestablished shortly after cardiac death. Ex vivo perfused human phonation was then achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles. MAIN OUTCOMES AND MEASURES: Phonation resulting from the graded states of neuromuscular stimulation was evaluated using high-speed vibratory imaging; the OQ was derived through digital kymography and glottal area waveform analysis. RESULTS: During constant glottal flow, a stepwise increase in adductor muscle group stimulation decreased the OQ. Quantitatively, OQ values decreased with increased stimulation levels from 2 V (OQ, 1) to 5 V (OQ, 0.68) and reached a lower limit of 8 V (OQ, 0.42). Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit. CONCLUSIONS AND RELEVANCE: To our knowledge, a negative association between adductor muscle group stimulation and phonatory OQ has been demonstrated for the first time in a neuromuscularly activated human larynx. Further experience with the ex vivo perfused human phonatory model will aid in systematically defining this causal relationship.

Three-Dimensional Optical Reconstruction of Vocal Fold Kinematics Using High-Speed Video With a Laser Projection System.

Vocal fold kinematics and its interaction with aerodynamic characteristics play a primary role in acoustic sound production of the human voice. Investigating the temporal details of these kinematics using high-speed videoendoscopic imaging techniques has proven challenging in part due to the limitations of quantifying complex vocal fold vibratory behavior using only two spatial dimensions. Thus, we propose an optical method of reconstructing the superior vocal fold surface in three spatial dimensions using a high-speed video camera and laser projection system. Using stereo-triangulation principles, we extend the camera-laser projector method and present an efficient image processing workflow to generate the three-dimensional vocal fold surfaces during phonation captured at 4000 frames per second. Initial results are provided for airflow-driven vibration of an ex vivo vocal fold model in which at least 75% of visible laser points contributed to the reconstructed surface. The method captures the vertical motion of the vocal folds at a high accuracy to allow for the computation of three-dimensional mucosal wave features such as vibratory amplitude, velocity, and asymmetry.

In vivo vocal fold cover layer replacement.

OBJECTIVES/HYPOTHESIS: An animal vocal fold replacement model is needed to investigate treatments for vocal fold scarring. We developed a rabbit surgical model, hypothesizing that orthotopic vocal fold cover implants would attach and survive. We further hypothesized that superficial scarring would be limited, allowing unimpeded vibration. STUDY DESIGN: Translational research: animal surgical study. METHODS: Rabbit vocal fold covers were excised and immediately reimplanted. After 4 weeks, rabbits were phonated and vibration was recorded with high-speed videography. Larynges were then excised, elastic moduli measured by indentation, and covers sectioned for histology. RESULTS: Five of six rabbits survived. Phonation was achieved in all, with mucosal waves evident. Elastic modulus did not differ significantly from contralateral uninjured control vocal folds. Histology demonstrated epithelial integrity, partial preservation of elastic fibers, and variable degrees of collagen deposition. CONCLUSIONS: Vocal fold cover implantation in rabbits is feasible, and grafts survived. Attachment onto the thyroarytenoid muscle prevented excessive scarring, maintained tissue mechanics, and preserved mucosal vibration. LEVEL OF EVIDENCE: NA.

Development of a time-dependent numerical model for the assessment of non-stationary pharyngoesophageal tissue vibrations after total laryngectomy.

Laryngeal cancer due to, e.g., extensive smoking and/or alcohol consumption can necessitate the excision of the entire larynx. After such a total laryngectomy, the voice generating structures are lost and with that the quality of life of the concerning patients is drastically reduced. However, the vibrations of the remaining tissue in the so called pharyngoesophageal (PE) segment can be applied as alternative sound generator. Tissue, scar, and geometric aspects of the PE-segment determine the postoperative substitute voice characteristic, being highly important for the future live of the patient. So far, PE-dynamics are simulated by a biomechanical model which is restricted to stationary vibrations, i.e., variations in pitch and amplitude cannot be handled. In order to investigate the dynamical range of PE-vibrations, knowledge about the temporal processes during substitute voice production is of crucial interest. Thus, time-dependent model parameters are suggested in order to quantify non-stationary PE-vibrations and drawing conclusions on the temporal characteristics of tissue stiffness, oscillating mass, pressure, and geometric distributions within the PE-segment. To adapt the numerical model to the PE-vibrations, an automatic, block-based optimization procedure is applied, comprising a combined global and local optimization approach. The suggested optimization procedure is validated with 75 synthetic data sets, simulating non-stationary oscillations of differently shaped PE-segments. The application to four high-speed recordings is shown and discussed. The correlation between model and PE-dynamics is ≥ 97%.

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.

THE ROLE OF THE THYROARYTENOID MUSCLE IN REGULATING GLOTTAL AIRFLOW AND GLOTTAL CLOSURE IN AN IN VIVO CANINE LARYNX MODEL.

This study investigated the effectiveness of individual laryngeal muscles in regulating the mean glottal flow and glottal closure pattern during phonation in an in vivo canine larynx model. Phonation experiments were performed with parametric stimulation of the thyroarytenoid (TA), lateral cricoarytenoid (LCA), interarytenoid (IA), and the cricothyroid (CT) muscles. For each stimulation level, the subglottal pressure was gradually increased to produce phonation. The subglottal pressure, the volume flow, and the outside acoustic pressure were measured together with high-speed recording of vocal fold vibration from a superior view. The results show that the TA muscle played a dominant role in regulating both the membranous glottal width and the glottal closure pattern during phonation, indicating an important role of the TA muscle in regulating voice quality. The TA muscle activation was also the most effective in regulating the mean glottal flow, and thus an important laryngeal adjustment in airflow conservation, particularly at high subglottal pressures or loud voice production, although increasing TA activation decreased the vocal intensity. This study also presented a complete set of data on muscular control of the glottal width and voice production, which can be used in validation of computational models of vocal fold posturing and voice production.

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.

Substitute voice production: quantification of PE segment vibrations using a biomechanical model.

After total larynx excision due to laryngeal cancer, the tracheoesophageal substitute tissue vibrations at the intersection between the pharynx and the esophagus [pharyngoesophageal segment (PE segment)] serve as voice generator. The quality of the substitute voice significantly depends on the vibratory characteristics of the PE segment. For improving voice rehabilitation, the relationship between the PE dynamics and the resulting substitute voice quality is a matter of particular interest. Precondition for a comprehensive analysis of this relationship is an objective quantification of the PE vibrations. For quantification purposes, a method is proposed, which is based on the reproduction of the tissue vibrations by means of a biomechanical model of the PE segment. An optimization procedure for an automatic determination of appropriate model parameters is suggested to adapt the model dynamics to tissue movements extracted from high-speed (HS) videos. The applicability of the optimization procedure is evaluated with ten synthetic data sets. A mean error of 8.2% for the determination of previously defined model parameters was achieved as well as an overall stability of 7.1%. The application of the model to six HS recordings presented a mean correlation of the vibration patterns of 82%.

Optical 3-D metric measurements of local vocal fold deformation characteristics in an in vitro setup.

Understanding vocal fold dynamics presents an essential part in treating voice disorders as it is the prerequisite to appropriate medical therapy. Various physical and numerical models exist for simulation purposes, all relying on simplified material parameters. To improve current approaches, data of realistic tissue behavior, i.e., in natural surroundings, have to be considered in model development. An in vitro setup was proposed for tensile tests combined with an optical method for precise, local and metrical 3-D measurements of distinctive surface points. Compared to previous 3-D reconstruction methods, the accuracy was improved tenfold. Vertically applied forces versus resulting deformation were measured for ten porcine vocal folds. Deformation characteristics of mucosa and the two-layer structure of mucosa and muscle (MM) were investigated at three distinctive locations along the vocal fold edge. The spring rates were represented by an exponential function. For equal deflections, an increasing spring rate from posterior to anterior for MM was measured. For solely mucosa, the spring rate decreased from the posterior to the middle and subsequently increased again. The MM-layer presented a stiffer deformation behavior than mucosa. For deformations higher than 1.5 mm, the spring rates for MM were more than twice as high as for mucosa. The investigations display the importance of considering both multilayers and local differences for the improvement of vocal fold models.

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.

Optical reconstruction of high-speed surface dynamics in an uncontrollable environment.

The ability to communicate with our voice can be regarded as the concatenation of the two processes "phonation" and "modulation." These take place in the larynx and palatal and oral region, respectively. During phonation the audible primary voice signal is created by mutual reaction of vocal folds with the exhaled air stream of the lungs. The underlying interactions of masses, fluids and acoustics have yet to be identified and understood. One part of the primary signal's acoustical source are vortex induced vibrations, as e.g., created by the Coandaeffect in the air stream. The development of these vorteces is determined by the shape and 3-D movements of the vocal folds in the larynx. Current clinical in vivo research methods for vocal folds do not deliver data of satisfactory quality for fundamental research, e.g., an endoscope is limited to 2-D image information. Based hereupon, a few improved methods have been presented, however delivering only selective 3-D information, either for a single point or a line. This stands in contrast to the 3-D motions of the entire vocal fold surface. More complex imaging methods, such as MRI, do not deliver information in real-time. Thus, it is necessary to develop an easily applicable, more improved examination method, which allows for 3-D data of the vocal folds surfaces to be obtained. We present a method to calibrate a 3-D reconstruction setup including a laser projection system and a high-speed camera. The setup is designed with miniaturization and an in vivo application in mind. The laser projection system generates a divergent grid of 196 laser dots by diffraction gratings. It is calibrated with a planar calibration target through planar homography. In general, the setup allows to reconstruct the topology of a surface at high frame rates (up to 4000 frames per second) and in uncontrollable environments, as e.g., given by the lighting situation (little to no ambient light) and varying texture (e.g., varying grade of reflection) in the human larynx. In particular, this system measures the 3-D vocal fold surface dynamics during phonation. Applied to synthetic data, the calibration is shown to be robust (error approximately 0.5 µm) regarding noise and systematic errors. Experimental data gained with a linear z -stage proved that the system reconstructs the 3-D coordinates of points with an error at approximately 15 µm. The method was applied exemplarily to reconstruct porcine and artificial vocal folds' surfaces during phonation. Local differences such as asymmetry between left and right fold dynamics, as well as global parameters, such as opening and closing speed and maximum displacements, were identified and quantified.