Georg Luegmair

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.

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.

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.

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.

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%.

In vivo vocal fold cover layer replacement.

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.

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.

Effects of thyroarytenoid muscle activation on phonation in an in vivo canine larynx model

Previous studies have shown that the thyroarytenoid (TA) muscle plays an important role in the control of vocal fold adduction and stiffness. The effects of TA stimulation on vocal fold vibration, however, are still unclear. In this study, the effects of TA muscle activation on phonation were investigated in an in vivo canine larynx model. Laryngeal muscle activation was achieved through parametric stimulation of the thyroarytenoid, the lateral cricoarytenoid (LCA), 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, without TA activation, phonation was limited to conditions of medium to high levels of LCA and CT activations. TA activation allowed phonation to occur at a much lower activation level of the LCA and CT muscles. Compared t...

Simultaneous Tracking of Vocal Fold Superior Surface Motion and Glottal Jet Dynamics

Synthetic aperture particle image velocimetry is used with an excised human vocal fold model to study the airflow between the vocal folds during voice production. A whole field, time-resolved, 3D description of the flow is presented over multiple cycles of vocal fold oscillations. The 3D flow data are synchronized with a 3D reconstruction of the superior surface of the vocal folds and with the subglottal pressure signal.© 2013 ASME