Understanding vocal fold mechanics is an integral part of voice research and synthetic vocal fold models are an essential tool in characterizing vocal fold mechanics. These models contain multiple layers with varying stiffness, much like human vocal folds. The purpose of this thesis is to improve the current models and modeling techniques, as well as investigate the impact of asymmetry on model vibration. A new design for an MRI-based model is detailed. This model has a more realistic geometry than the simplified models and mimics some of the vibratory characteristics observed in human vocal folds. The MRI-based model was used to investigate left-right stiffness asymmetry in multiple layers of the model. A zipper-like motion was observed during vibration of the MRI-based models. A phase shift was present in the asymmetric models, with the less stiff side leading the stiffer side. A new expendable mold fabrication process is described. This new process provides more freedom in designing vocal fold models and experiments. Additionally, the new process enables fabrication of models without the use of release agent, a factor which has, in the past, adversely impacted manufacturing yield and prohibited the incorporation of certain biological materials into the synthetic models. The new process also allows for more convenient geometry variation than what has previously been feasible. Finally, the new process was used to investigate cover layer geometry variation and asymmetry in a simplified model. Cover layer thickness was found to be a significant factor in governing the motion of the vocal fold model. Anterior-posterior asymmetry was found to induce the same zipper-like motion observed in the MRI-based models.

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<p>Systemic dehydration negatively alters epithelial cell junction markers and inflammatory mediators  in  vocal  fold  tissue.  In other  organs,  dehydration canhave the  following  suboptimal outcomes; prolonged inflammation and delayed re-epithelization.It is surprising that the adverse role  of  systemic  dehydration  in  vocal  fold  healing  has  not  been  directly  demonstrated  when dehydration has the potential to alter recovery following injury. The similarities between healing in dermal and mucosal tissue indicate an increased need to understand the effects of dehydration onvocal fold recovery.</p> <p>Suboptimal vocal fold healing can have downstream consequences on vibratory function. Before functional voice changes can be delineated, there is a need to characterize the cellular interactions of  systemic  dehydration  and  vocal  fold  healing.   The  overarching  research  aim  of  this dissertation is to investigate the interaction of systemic dehydration and vocal fold healing on the gene expression of inflammatory and epithelial cell junction markers, following acute vocal  fold  injury.Gene expressionoutcomes werecompared  in four  groups;systemically-dehydrated,and  euhydrated  rats with minor,  bilateral  vocal  fold  injuriesand  systemically-dehydrated  and  euhydrated  rats  without  vocal  fold  injuries (N=9/group). We  hypothesized  that systemic  dehydration(compared  to  euhydration)would  cause an upregulation  of  pro  and  anti-inflammatory mediators with injury, but adownregulation of these inflammatory markers in the absence  of  injury.  We  also  hypothesized  that  systemic  dehydration(compared  to  euhydration)would cause a downregulation of epithelial cell junction markers with and without injury, butthat the effects of dehydration would be exacerbated with injury. </p> <p>We  found  that  the  gene  expression  of  pro-inflammatory  cytokines  was  differentially expressed  in  systemically-dehydrated  injured  vocal  old  tissue  when  compared  to  systemically-euhydrated injured vocal  fold  tissue, 24  hours  after  vocal  fold  injury. These  data  lay  the groundwork for future studies characterizing the later stages of interaction of systemic dehydration and injury.</p>

One of the primary objectives of voice research is to better understand the biomechanics of voice production and how changes in properties of the vocal folds (VFs) affect voice ability and quality. Synthetic VF models provide a way to observe how changes in geometry and material property affect voice biomechanics. This thesis seeks to evaluate an approach of using a genetic algorithm to design synthetic VF models in three ways: first, through the development of a computationally cost-effective 3D vocal fold model; second, by creating and optimizing a variation of this model; and third, by validating the approach. To reduce computation times, a user-defined function (UDF) was implemented in low-fidelity 2D and 3D computational VF models. The UDF replaced the conventional meshed fluid domain with the mechanical energy equation. The UDF was implemented in the commercial finite element code ADINA and verified to produce results that were similar to those of 2D and 3D VF models with meshed fluid domains. Computation times were reduced by 86% for 2D VF models and 74% for 3D VF models while core vibratory characteristic changes were less than 5%. The results from using the UDF demonstrate that computation times could be reduced while still producing acceptable results. A genetic algorithm optimizer was developed to study the effects of altering geometry and material elasticity on frequency, closed quotient (CQ), and maximum flow declination rate (MFDR). The objective was to achieve frequency and CQ values within the normal human physiological range while maximizing MFDR. The resulting models enabled an exploration of trends between objective and design variables. Significant trends and aspects of model variability are discussed. The results demonstrate the benefit of using a structured model exploration method to create models with desirable characteristics. Two synthetic VF models were fabricated to validate predictions made by models produced by the genetic algorithm. Fabricated models were subjected to tests where frequency, CQ, and sound pressure level were measured. Trends between computational and synthetic VF model responses are discussed. The results show that predicted frequency trends between computational and synthetic models were similar, trends for closed quotient were inconclusive, and relationships between MFDR and sound pressure level remained consistent. Overall, while discrepancies between computational and synthetic VF model results were observed and areas in need of further study are noted, the study results provide evidence of potential for using the present optimization method to design synthetic VF models.

Voiced communication plays a fundamental role in society. Voice research seeks to improve understanding of the fundamental physics governing voice production, with the eventual goal of improving methods to diagnose and treat voice disorders. For this thesis, three different aspects of voice production research were studied. First, porcine vocal fold medial surface geometry was determined, and the three-dimensional geometric distortion induced by freezing the larynx, especially in the region of the vocal folds, was quantified. It was found that porcine vocal folds are qualitatively geometrically similar to canine and human vocal folds, as well as commonly used models, and that freezing of tissue in the larynx causes distortion of around 5%. Second, a setup of multiple high-resolution cameras and a stereo-endoscopy system simultaneously recorded positions on the superior surface of synthetic, self-oscillating vocal fold models to estimate the error in the measurement of the three-dimensional location by the stereo-endoscopy system. The error was found to be low in the transverse plane, whereas the error was relatively large in the inferior-superior direction, suggesting that the stereo-endoscope is applicable for in vivo measurements of absolute distances of the glottis in the transverse plane such as glottal length, width, and area. Third, a function for strain-varying Poisson's ratio for silicone was developed from experimental data. It is anticipated that the findings herein can aid voice researchers as they study voice production, leading to improved voice care.

Vocal folds are the twin in-folding of the mucous membrane stretched horizontally across the larynx. They vibrate modulating the constant air flow initiated from the lungs. The pulsating pressure wave blowing through the glottis is thus the source for voiced speech production. Study of vocal fold dynamics during voicing are critical for the treatment of voice pathologies. Since the vocal folds move at 100 - 350 cycles per second, their visual inspection is currently done by strobosocopy which merges information from multiple cycles to present an apparent motion. High Speed Digital Laryngeal Imaging(HSDLI) with a temporal resolution of up to 10,000 frames per second has been established as better suited for assessing the vocal fold vibratory function through direct recording. But the widespread use of HSDLI is limited due to lack of consensus on the modalities like features to be examined. Development of the image processing techniques which circumvents the need for the tedious and time consuming effort of examining large volumes of recording has room for improvement. Fundamental questions like the required frame rate or resolution for the recordings is still not adequately answered. HSDLI cannot get the absolute physical measurement of the anatomical features and vocal fold displacement. This work addresses these challenges through improved signal processing. A vocal fold edge extraction technique with subpixel accuracy, suited even for hard to record pediatric population is developed first. The algorithm which is equally applicable for pediatric and adult subjects, is implemented to facilitate user inspection and intervention. Objective features describing the fold dynamics, which are extracted from the edge displacement waveform are proposed and analyzed on a diverse dataset of healthy males, females and children. The sampling and quantization noise present in the recordings are analyzed and methods to mitigate them are investigated. A customized Kalman smoothing and spline interpolation on the displacement waveform is found to improve the feature estimation stability. The relationship between frame rate, spatial resolution and vibration for efficient capturing of information is derived. Finally, to address the inability to measure physical measurement, a structured light projection calibrated with respect to the endoscope is prototyped.

Asymmetries of the vocal folds and vocal fold vibration are key features underlying unilateral vocal fold motion impairment (VFMI). The knowledge of what particular asymmetries contribute to breathy voice and which asymmetries must be eliminated to re-establish normal voice will be important to improving evaluation and treatment of VFMI. It was hypothesized that several structural and vibratory asymmetries should lead to predictable changes in the glottal area, flow, and acoustic waveforms, and subsequently a perceived breathy voice quality. The purpose of this project was threefold: 1) to determine how specific vocal fold structural and vibratory asymmetries alter vocal function and perceived voice quality, 2) to determine the improvement in vocal function and voice quality in an abnormal voice with elimination of individual asymmetries, and 3) to develop a battery of vocal function measures that vary with dysphonia in a predictable manner. The approach was to use a computational kinematic model of vocal fold vibration that allows for differential left/right control of parameters such as vocal fold adduction, medial surface bulging, vibratory nodal point, phase, amplitude of vibration, and fundamental frequency. The resultant signals were subjected to aerodynamic and acoustic measurement as well as perceptual rating of voice quality. Results revealed that the degree of vocal process separation was the most influential parameter tested, though asymmetry of bulging, nodal point ratio, and starting phase worsened normal voice quality. Conversely, increased symmetry of bulging, nodal point ratio, amplitude of vibration and starting phase improved disordered voice quality. The amount of improvement to disordered voices varied based on the number of other asymmetries present. None of the six vocal function measures tested were primarily responsive to one particular model parameter, though four measures generally decreased as vocal process separation increased: maximum flow declination rate (MFDR), spectral slope (B0-B2), cepstral peak prominence (CPP), and harmonics-to-noise ratio (HNR). Two of the measures, MFDR and CPP, co-varied with each of the five parameters and robustly correlated with perceived severity.

Understanding the involvement of the central nervous system (CNS) in voice production is essential to incorporating principles of neuroplasticity into therapeutic practice for voice disorders. Early steps to attaining this goal require the identification of specific neural biomarkers of the changes occurring in the CNS from a voice disorder and its subsequent treatment. In the absence of an adequate animal vocalization model, the larynx has not been acutely and reversibly perturbed to concurrently examine the effect on both peripheral and central processing of the altered input/output. Using a unique, reversible perturbation approach, it was the purpose of this study to perturb the larynx to mimic a voice disorder and study short-term neuroplastic response. Functional magnetic resonance imaging (fMRI) was the neuroimaging tool of choice for this study due to its superior spatial and temporal resolution. The voice was perturbed by anesthetizing the right recurrent laryngeal nerve, with a solution of lidocaine hydrochloride and epinephrine to induce a temporary right vocal fold paralysis. The paralysis lasted for approximately 90 minutes and had an overt presentation similar to that of a true vocal fold paralysis. Behavioral and fMRI data were obtained at three time points- baseline, during the vocal fold paralysis and one hour after recovery. Patterns of activity on fMRI during the three time points were found to be distinct on both subjective examination and statistical analysis. The regions of interest examined had distinct trends in activity as a function of the paralysis. Interestingly, males and females responded differently to the paralysis and its subsequent recovery. Strong correlation was not observed between the behavioral measures and fMRI activity reflecting a disparity between the overt presentation and recovery of vocal fold paralysis and cortical activity as seen on fMRI. The fictive paralysis model employed in this study provided a perturbation model for phonation that allowed us to examine behavioral and central neural correlates for disordered phonation in a controlled environment. Although this data is representative of acute changes from a transient paralysis, it provides an insight into the response of the cortex to sudden perturbation at the peripheral phonatory mechanism.

Tissue engineering (TE) approaches have emerged as an alternative to traditional tissue and organ replacements. The aim of this work was to contribute to the understanding of the effects of cell-material and endothelial cell (EC) paracrine signaling on cell responses using poly(ethylene glycol) diacrylate (PEGDA) hydrogels as a material platform. Three TE applications were explored. First, the effect of glycosaminoglycan (GAG) identity was evaluated for vocal fold restoration. Second, the influence of GAG identity was explored and a novel approach for stable endothelialization was developed for vascular graft applications. Finally, EC paracrine signaling in the presence of cyclic stretch, and hydrophobicity and inorganic content were studied for osteogenic applications. In terms of vocal fold restoration, it was found that vocal fold fibroblast (VFF) phenotype and extracellular matrix (ECM) production were impacted by GAG identity. VFF phenotype was preserved in long-term cultured hydrogels containing high molecular weight hyaluronan (HAHMW). Furthermore, collagen I deposition, fibronectin production and smooth muscle alpha-actin (SM-alpha-actin) expression in PEG-HA, PEG-chondroitin sulfate C and PEG- heparan sulfate (HS) gels suggest that CSC and HS may be undesirable for vocal fold implants. Regarding vascular graft applications, the impact of GAG identity on smooth muscle cell (SMC) foam cell formation was explored. Results support the increasing body of literature that suggests a critical role for dermatan sulfate (DS)-bearing proteoglycans in early atherosclerosis. In addition, an approach for fabricating bi-layered tissue engineering vascular grafts (TEVGs) with stable endothelialization was validated using PEGDA as an intercellular "cementing" agent between adjacent endothelial cells (ECs). Finally, mesenchymal stem cell (MSC) differentiation toward osteogenic like cells was evaluated. ECM and cell phenotypic data showed that elevated scaffold inorganic content and hydrophobicity were indeed correlated with increased osteogenic differentiation. Moreover, the present results suggest that EC paracrine signaling enhances MSC osteogenesis in the presence of cyclic stretch.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-08-19T12:56:35Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO DE MESTRADO.pdf: 5645546 bytes, checksum: 320bd7e7f07722da2414b1f05d58a263 (MD5) / Made available in DSpace on 2016-08-19T12:56:35Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO DE MESTRADO.pdf: 5645546 bytes, checksum: 320bd7e7f07722da2414b1f05d58a263 (MD5) Previous issue date: 2016-03-02 / Estudos recentes têm apontado para a importância da fonoterapia como tratamento primário do pólipo, com posterior indicação cirúrgica em situações de persistência da lesão e insatisfação no que se refere à qualidade vocal resultante. O objetivo dessa dissertação foi verificar a efetividade da fonoterapia com ênfase na técnica de vibração sonorizada de lábios e língua e orientações de saúde vocal no tratamento do pólipo vocal. A amostra foi constituída por 10 adultos de ambos os sexos com diagnóstico de pólipo, avaliados através de videolaringoscopia, questionário de hábitos vocais e sintomas, autoavaliação vocal e análise perceptivo-auditiva e acústica da voz. Os participantes foram alocados em dois grupos (controle e tratamento). A fonoterapia, aplicada ao grupo de tratamento, consistiu de 10 sessões semanais, com duração de 30 a 45 minutos cada. Os pacientes submetidos à fonoterapia apresentaram melhora da qualidade vocal nos parâmetros de grau de severidade vocal, rugosidade e soprosidade (p=0,043), redução de jitter (p=0,034) e aumento na proporção sinal glótico/ruído excitado (p=0,028). Houve ainda redução no tamanho do pólipo (p=0,043); redução dos sintomas associados (p=0,034) e melhora na autoavaliação vocal (p=0,034). O grupo controle não apresentou modificação vocal ou laríngea. A fonoterapia proporcionou reabsorção da lesão ou diminuição do tamanho do pólipo associada à adaptação vocal em três dos cinco participantes, tendo evitado a cirurgia em quatro deles, sugerindo efetividade da fonoterapia com ênfase na vibração de lábios e língua no tratamento do pólipo vocal. / Recent studies have indicated the importance of speech therapy as the primary treatment of polyps, with subsequent surgical situations indicated persistence of the lesion and dissatisfaction in regard to the resultant voice quality. The purpose of this study was to investigate the effectiveness of speech therapy with emphasis on the sonorous lips or tongue vibration technique and vocal health guidelines in the treatment of vocal polyps. The sample consisted of 10 adults of both sexes diagnosed with polyps on the vocal folds, evaluated through laryngoscopy, vocal habits and symptoms questionnaire, vocal self-assessment and perceptual and acoustic analysis of voice. Speech therapy applied on the treatment group consisted of 10 weekly sessions, lasting 30-45 minutes each. Participants were divided in two groups (control and treatment). Patients undergoing speech therapy showed improvement of voice quality in the parameters of grade of vocal severity, roughness and breathiness (p = 0.043), reduced jitter (p = 0.034) and increase in proportion to signal glottal / excited noise (p = 0.028). There was also a reduction in polyp size (p = 0.043), reduction in associated symptoms and improved vocal self-assessment (p = 0.034). The control group showed no vocal or laryngeal modification. Speech therapy provided reabsorption of injury or decrease in polyp size associated with vocal adaptation in three of the five participants, avoided surgery in four of them, suggesting effectiveness of speech therapy with emphasis on lips and tong trills in the treatment of vocal polyp.