An Integrated Experimental-Computational Study of Vocal Fold Vibration in Type I Thyroplasty.

Subject-specific computational modeling of vocal fold (VF) vibration was integrated with an ex vivo animal experiment of type 1 thyroplasty to study the effect of the implant on the vocal fold vibration. In the experiment, a rabbit larynx was used to simulate type 1 thyroplasty, where one side of the vocal fold was medialized with a trans-muscular suture while the other side was medialized with a silastic implant. Vocal fold vibration was then achieved by flowing air through the larynx and was filmed with a high-speed camera. The three-dimensional computational model was built upon the pre-operative scan of the laryngeal anatomy. This subject-specific model was used to simulate the vocal fold medialization and then the fluid-structure interaction (FSI) of the vocal fold. Model validation was done by comparing the vocal fold displacement with postoperative scan (for medialization), and by comparing the vibratory characteristics with the high-speed images (for vibration). These comparisons showed the computational model successfully captured the effect of the implant and thus has the potential for presurgical planning.

Acute Effects of Systemic Glucocorticoids on the Vocal Folds in a Pre-Clinical Model.

OBJECTIVES/HYPOTHESIS: Systemic glucocorticoids (GC)s are employed to treat various voice disorders. However, GCs have varying pharmacodynamic properties with adverse effects ranging from changes in epithelial integrity, skeletal muscle catabolism, and altered body weight. We sought to characterize the acute temporal effects of systemic dexamethasone and methylprednisolone on vocal fold (VF) epithelial glucocorticoid receptor (GR) nuclear translocation, epithelial tight junction (ZO-1) expression, thyroarytenoid (TA) muscle fiber morphology, and body weight using an established pre-clinical model. We hypothesized dexamethasone and methylprednisolone will elicit changes in VF epithelial GR nuclear translocation, epithelial ZO-1 expression, TA muscle morphology, and body weight compared to placebo-treated controls. METHODS: Forty-five New Zealand white rabbits received intramuscular injections of methylprednisolone (4.5 mg; n = 15), dexamethasone (450 µg; n = 15), or volume matched saline (n = 15) into the iliocostalis/longissimus muscle for 6 consecutive days. Vocal folds from 5 rabbits from each treatment group were harvested at 1-, 3-, or 7 days following the final injection and subjected to immunohistochemistry for ZO-1 and GR as well as TA muscle fiber cross-sectional area (CSA) measures. RESULTS: Dexamethasone increased epithelial GR nuclear translocation and ZO-1 expression 1-day following injections compared to methylprednisolone (P = .024; P = .012). Dexamethasone and methylprednisolone increased TA CSA 1-day following injections (P = .011). Methylprednisolone decreased body weight 7 days following injections compared to controls (P = .004). CONCLUSIONS: Systemic dexamethasone may more efficiently activate GR in the VF epithelium with a lower risk of body weight loss, suggesting a role for more refined approaches to GC selection for laryngeal pathology.

Subject-Specific Modeling of Implant Placement for Type I Thyroplasty Surgery.

Type I thyroplasty is widely used to improve voice production in patients affected by unilateral vocal fold paralysis. Almost two-thirds of laryngologists report using Silastic® implants to medialize the vocal fold, with implant size, shape, and location determined experientially. However, post-surgical complications arising from this procedure (extrusion, migration, resizing) necessitate revision in 4.5-16% of patients. To improve initial surgical outcomes, we have developed a subject-specific modeling tool, PhonoSim, which uses model reconstruction from MRI scans to predict the optimal implantation location. Eleven vocal fold sample sides from eight larynges of New Zealand white rabbits were randomized to two groups: PhonoSim informed (n = 6), and control (no model guidance, n = 5). Larynges were scanned ex vivo in the abducted configuration using a vertical-bore 11.7 T microimaging system, and images were used for subject-specific modeling. The PhonoSim tool simulated vocal fold adduction for multiple implant location placements to evaluate vocal fold adduction at the medial surface. The best implant placement coordinates were output for the 6 samples in the PhonoSim group. Control placements were determined by the same surgeon based on anatomical landmarks. Post-surgical MRI scans were performed for all samples to evaluate medialization in implanted vocal folds. Results show that PhonoSim-guided implantation achieved higher vocal fold medialization relative to controls (28 to 55% vs. - 29 to 39% respectively, in the glottal area reduction), suggesting that this tool has the potential to improve outcomes and revision rates for type I thyroplasty.

Custom Laser-Cut Silastic® Implants for Type I Thyroplasty in a Preclinical Model.

This study aimed to produce customized silicone elastomer implants of varied size and shape for optimization of type I thyroplasty procedures in a rabbit model. Computer-aided design models of different implant designs were designed and used to program laser cutting of a medical-grade Silastic® sheet. Laser-cut implants were produced rapidly and cost-efficiently. Surgical implantation demonstrated vocal fold medialization and phonation in 5 test subjects. This technique may provide a low-cost alternative or adjunct method to hand-carving or commercial implants.

Acute In Vitro and In Vivo Effects of Dexamethasone in the Vocal Folds: a Pilot Study.

OBJECTIVES/HYPOTHESIS: Glucocorticoids (GC)s are commonly employed to treat vocal fold (VF) pathologies. However, VF atrophy has been associated with intracordal GC injections. Dexamethasone-induced skeletal muscle atrophy is well-documented in other tissues and believed to be mediated by increased muscle proteolysis via upregulation of Muscle Ring Finger (MuRF)-1 and Atrogin-1. Mechanisms of dexamethasone-mediated VF atrophy have not been described. This pilot study employed in vitro and in vivo models to investigate the effects of dexamethasone on VF epithelium, thyroarytenoid (TA) muscle, and TA-derived myoblasts. We hypothesized that dexamethasone will increase atrophy-associated gene expression in TA muscle and myoblasts and decrease TA muscle fiber size and epithelial thickness. STUDY DESIGN: In vitro, pre-clinical. METHODS: TA myoblasts were isolated from a female Sprague-Dawley rat and treated with 1 µM dexamethasone for 24-h. In vivo, 15 New Zealand white rabbits were randomly assigned to three treatment groups: (1) bilateral intracordal injection of 40 µL dexamethasone (10 mg/ml; n = 5), (2) volume-matched saline (n = 5), and (3) untreated controls (n = 5). Larynges were harvested 7-days post-injection. Across in vivo and in vitro experimentation, MuRF-1 and Atrogin-1 mRNA expression were measured via RT-qPCR. TA muscle fiber cross-sectional area (CSA) and epithelial thickness were also quantified in vivo. RESULTS: Dexamethasone increased MuRF-1 gene expression in TA myoblasts. Dexamethasone injection, however, did not alter atrophy-associated gene expression, TA CSA, or epithelial thickness in vivo. CONCLUSION: Dexamethasone increased atrogene expression in TA myoblasts, providing foundational insight into GC induced atrophic gene transcription. Repeated dexamethasone injections may be required to elicit atrophy in vivo. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2264-2270, 2023.

Subject-Specific Computational Fluid-Structure Interaction Modeling of Rabbit Vocal Fold Vibration.

A full three-dimensional (3D) fluid-structure interaction (FSI) study of subject-specific vocal fold vibration is carried out based on the previously reconstructed vocal fold models of rabbit larynges. Our primary focuses are the vibration characteristics of the vocal fold, the unsteady 3D flow field, and comparison with a recently developed 1D glottal flow model that incorporates machine learning. The 3D FSI model applies strong coupling between the finite-element model for the vocal fold tissue and the incompressible Navier-Stokes equation for the flow. Five different samples of the rabbit larynx, reconstructed from the magnetic resonance imaging (MRI) scans after the in vivo phonation experiments, are used in the FSI simulation. These samples have distinct geometries and a different inlet pressure measured in the experiment. Furthermore, the material properties of the vocal fold tissue were determined previously for each individual sample. The results demonstrate that the vibration and the intraglottal pressure from the 3D flow simulation agree well with those from the 1D flow model based simulation. Further 3D analyses show that the inferior and supraglottal geometries play significant roles in the FSI process. Similarity of the flow pattern with the human vocal fold is discussed. This study supports the effective usage of rabbit larynges to understand human phonation and will help guide our future computational studies that address vocal fold disorders.

Numerical and experimental investigations on vocal fold approximation in healthy and simulated unilateral vocal fold paralysis.

We have developed a novel surgical/computational model for the investigation of unilateral vocal fold paralysis (UVFP) which will be used to inform future in silico approaches to improve surgical outcomes in type I thyroplasty. Healthy phonation (HP) was achieved using cricothyroid suture approximation on both sides of the larynx to generate symmetrical vocal fold closure. Following high-speed videoendoscopy (HSV) capture, sutures on the right side of the larynx were removed, partially releasing tension unilaterally and generating asymmetric vocal fold closure characteristic of UVFP (sUVFP condition). HSV revealed symmetric vibration in HP, while in sUVFP the sutured side demonstrated a higher frequency (10 - 11%). For the computational model, ex vivo magnetic resonance imaging (MRI) scans were captured at three configurations: non-approximated (NA), HP, and sUVFP. A finite-element method (FEM) model was built, in which cartilage displacements from the MRI images were used to prescribe the adduction and the vocal fold deformation was simulated before the eigenmode calculation. The results showed that the frequency comparison between the two sides were consistent with observations from HSV. This alignment between the surgical and computational models supports the future application of these methods for the investigation of treatment for UVFP.

Medialization Laryngoplasty: A Review for Speech-Language Pathologists.

Purpose The purpose of this study is to familiarize speech-language-pathologists with the current state of the science regarding medialization laryngoplasty in the treatment of voice disorders, with emphasis on current evidence-based practice, voice outcomes, and future directions for research. Method A literature review was performed in PubMed and Embase using the keywords vocal fold/cord and laryngoplasty, thyroplasty, augmentation, or laryngeal framework. Articles published between 2010 and 2020 were reviewed for data about clinical applications, technical approach, voice-related outcomes, and basic science or clinical innovations with the potential to improve patient care. A synthesis of data was performed from articles meeting the outlined search criteria. Conclusions As key members in the multidisciplinary care of voice disorders, speech-language pathologists need to be informed of current research in medialization laryngoplasty, a procedure commonly used for patients with glottic insufficiency. Advances in anesthetic technique, office-based procedures, and the development of materials with increased bio-tolerability over the past decade have led to innovations in treatment and improved patient outcomes. Recent applications of computational and bioengineering approaches have the potential to provide new directions in the refinement of currently available techniques and the improvement of patient-based treatment outcomes.

Evaluation of Diffusional Characteristics and Microstructure in Unilateral Vocal Fold Paralysis Using Diffusion Tensor Imaging.

OBJECTIVE: To investigate the value of diffusion tensor imaging (DTI) in the evaluation of vocal fold tissue microstructure after recurrent laryngeal nerve (RLN) injury. METHODS: Six canines were divided into 2 groups: a unilateral vocal fold paralysis group (n = 4) and a control group (n = 2). The RLN was cut in the unilateral vocal fold paralysis group, and no intervention was applied in the control group. After 4 months, the canines' larynges were removed and placed in a small animal magnetic resonance imaging (MRI) system (9.4T BioSpec MRI; Bruker, Germany). After scanning, the vocal folds were isolated, sectioned, and stained. The slides were then analyzed for the cross-sectional area and muscle fiber density through feature extraction technology. Pearson correlation analysis was performed on the DTI scan and histological section extraction results. RESULTS: In the vocal fold muscle layer, the fractional anisotropy (FA) of the unilateral RLN injury group was higher than that of the control group, and the Tensor Trace was lower than that of the control group. This difference was statistically significant, P < .05. In the lamina propria, the FA of the unilateral RLN injury group was lower than that of the control group, P > .05, and the Tensor Trace was lower than that of the control group, P < .05. The muscle fiber cross-sectional area of the RLN injury group was significantly smaller than the control group with statistical significance, P < .05, and the density of muscle fibers was lower, P < .05. The correlation coefficient between FA and the cross-sectional area was -0.838, P = .002, and .726; P = .017 between Tensor Trace and the cross-sectional area. CONCLUSION: Diffusion tensor imaging is an effective method to assess the changes in the microstructure of atrophic vocal fold muscle tissue after RLN injury.

Compensatory Movement of Contralateral Vocal Folds in Patients With Unilateral Vocal Fold Paralysis.

OBJECTIVES: Previous studies of subjects with unilateral vocal fold paralysis (UVFP) as observed in a positron emission tomography-computed tomography (PET-CT) examination have demonstrated false positive results in the contralateral cricoarytenoid, in which the metabolism may be higher. This area may also be the site of contralateral compensatory movement in these patients. In this study, we compared the adduction speed of the contralateral vocal folds in patients with UVFP and in healthy subjects as measured by the stroboscopic laryngoscope frame rate. This study aimed to explore the contralateral compensatory movement of the vocal folds in subjects with UVFP. METHODS: (1) We collected visual data from 14 patients with UVFP and 14 healthy subjects through a stroboscopic laryngoscope. These subjects were divided into a vocal fold paralysis group and a control group, and we analyzed the excessive adduction of the contralateral vocal folds in the vocal fold paralysis group by examining vocal fold movement speed (pixels/s) as featured in a stroboscopic laryngoscope video. (2) We analyzed the uptake of 18-FDG in the posterior vocal fold from positron emission tomography-computed tomography imaging from four subjects with UVFP and 12 healthy subjects. An independent sample t test and a χ2 test were used to compare data. RESULTS: Four subjects with UVFP had a higher metabolic rate in the contralateral cricoarytenoid joints, with a significant difference between the two groups, P < 0.05. Fifty percent of the cases of contralateral adduction of the vocal folds in the subjects with UVFP adducted past the midline, with a significant difference between the two groups, P < 0.05. The contralateral adduction of the vocal folds in subjects with UVFP had shorter video frames and higher adduction speed than the control group, and the difference was statistically significant, P < 0.05. There were fewer vocal fold abduction video frames and higher abduction speed of the healthy side of the vocal fold in subjects with UVFP than the control group, but there was no statistically significant difference, P > 0.05. CONCLUSION: Subjects with UVFP exhibited faster adduction compensation in the contralateral vocal folds, and the contralateral cricoarytenoid joint's metabolism in subjects with UVFP was higher. These data may help clarify the diagnostic criteria for laryngeal nerve damage.

Spatial Motion of Arytenoid Cartilage Using Dynamic Computed Tomography Combined with Euler Angles.

OBJECTIVE: To investigate the feasibility of dynamic computed tomography in recording and describing the spatial motion characteristics of the arytenoid cartilage. METHODS: Dynamic computed tomography recorded the real-time motion trajectory of the arytenoid cartilage during inspiration and phonation. A stationary coordinate system was established with the cricoid cartilage as a reference and a motion coordinate system was established using the movement of the arytenoid cartilage. The Euler angles of the arytenoid cartilage movement were calculated by transformation of the two coordinate systems, and the spatial motion characteristics of the arytenoid cartilage were quantitatively studied. RESULTS: Displacement of the cricoid cartilage was primarily inferior during inspiration. During phonation, the displacement was mainly superior. When the glottis closed, the superior displacement was about 5-8 mm within 0.56 s. During inspiration, the arytenoid cartilage was displaced superiorly approximately 1-2 mm each 0.56 s. The rotation angle was subtle with slight rotation around the XYZ axis, with a range of 5-10 degrees. During phonation, the displacement of the arytenoid cartilage was mainly inferior (about 4-6 mm), anterior (about 2-4 mm) and medial (about 1-2 mm). The motion of the arytenoid cartilage mainly consisted of medial rolling, and there was an alternating movement of anterior-posterior tilting. The arytenoid cartilage rolled medially (about 20-40 degrees within 0.56 s), accompanied by anterior-posterior tilting (about 15-20 degrees within 0.56 s). CONCLUSION: Dynamic computed tomography recordings of arytenoid cartilage movement can be combined with Euler transformations as a tool to study the spatial characteristics of laryngeal structures during phonation. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E646-E653, 2020.