Publications by authors named "Jack J Jiang"

189 Publications

The integrity and barrier function of porcine vocal fold epithelium: its susceptibility to damage by deoxycholic acid compared with pepsin.

Eur Arch Otorhinolaryngol 2021 Jul 22. Epub 2021 Jul 22.

The Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Purpose: In this study, we aim to systematically evaluate the damaging role of gastric (pepsin and acid) and duodenal ingredients (bile acids) on vocal fold epithelium in excised porcine larynges.

Methods: Fresh ex vivo porcine larynges were exposed to one of five experimental conditions for 1 h. These conditions will be referred to as alkaline deoxycholic acid, acidic pepsin, acid pH3 only, acid pH5 only, and control, respectively. A Franz diffusing cell was used to evaluate the barrier function of vocal fold epithelium by measuring the permeability to fluorescein isothiocyanate dextran of 4 kDa. Histological changes were observed using transmission electron microscopy.

Results: After immersing the fresh porcine larynges in the five solution groups, we found that the vocal fold epithelium in the deoxycholic acid group had more permeability to FD4 than the pepsin group (P < 0.001). Fragmentation and desquamation of dead cell layers were observed in both the pepsin and deoxycholic acid groups, but were more severe in the deoxycholic acid group than the pepsin group. The thickness of the dead epithelial cell layer gradually increased with increasing acid concentration (P < 0.05). Additionally, the thickness of the dead epithelial cell layer in the deoxycholic acid group was significantly higher than that in the pepsin group (P < 0.01).

Conclusion: Deoxycholic acid in a weakly acidic condition is more likely than pepsin to induce apoptosis in ex vivo porcine vocal fold epithelium, destroy the link proteins between epithelial cells, and affect their integrity and barrier function.
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http://dx.doi.org/10.1007/s00405-021-06997-xDOI Listing
July 2021

Evaluating the Voice Type Component Distributions of Excised Larynx Phonations at Three Subglottal Pressures.

J Speech Lang Hear Res 2021 05 22;64(5):1447-1456. Epub 2021 Apr 22.

Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health.

Purpose The excised canine larynx provides an advantageous experimental framework in the study of voice physiology. In recent years, signal processing methods have been applied to analyze phonations in excised canine larynx experiments. However, phonations have a highly complex and nonstationary nature corresponding to different proportions of regular and chaotic signal elements. Current nonlinear dynamic methods that are used to assess the degree of irregularity in the voice fail to recognize the distribution of voice type components (VTCs). Method Based on measures of intrinsic dimension, this article presents a method to analyze the VTC distribution of phonations in excised canine larynx experiments. Thirty-nine phonation samples from 13 excised canine larynges at three different subglottal pressures were analyzed. Results Phonation produced with subglottal pressures above phonation instability pressure (PIP) and below phonation threshold pressure (PTP) resulted in high proportions of Voice Types 3 and 4, characterized by chaotic and noisy signals. Phonation produced with pressure between PTP and PIP contained mostly Type 1 voice, characterized by a regular and nearly periodic signal. Mean proportions of all VTCs varied significantly in comparisons of phonations produced with Sub-PTP and PTP as well as in comparisons of phonations produced with PTP and PIP. Conclusions Across all VTCs, the VTC profiles of normal and abnormal phonation differ significantly. Normal phonation is strongly associated with VTC (Voice Type Component 1), whereas abnormal phonation exhibits increased VTC (Voice Type Component 4). The study further demonstrates the ability of intrinsic dimension to successfully detect multiple voice types in an acoustic signal and highlights the need for expanded use of intrinsic dimension in human voice. Supplemental Material https://doi.org/10.23641/asha.14417585.
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http://dx.doi.org/10.1044/2021_JSLHR-20-00429DOI Listing
May 2021

Spectral arc length as a method to quantify pharyngeal high-resolution manometric curve smoothness.

Neurogastroenterol Motil 2021 Apr 20:e14122. Epub 2021 Apr 20.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Background: Pharyngeal high-resolution manometry (HRM) has emerged over the last decade as a valuable assessment tool for oropharyngeal dysphagia. Data analysis thus far has focused primarily on measures of pressure and duration within key anatomic regions. We apply spectral arc length (SPARC), a dimensionless metric for quantifying smoothness felt to indirectly reflect neuromuscular coordination, as a new method of describing manometric curves. We then use it to distinguish swallows from healthy subjects and those with dysphagia related to stroke.

Methods: Previously collected pharyngeal HRM data from eight subjects with history of stroke and eight age- and sex-matched controls were reviewed. Receiver operating characteristic (ROC) analysis was used to optimize SPARC inputs. SPARC was then computed for the velopharynx, tongue base, hypopharynx, and upper esophageal sphincter (UES), and the values were compared between the two subject groups.

Results: Optimized parameter settings yielded an ROC curve with area under the curve (AUC) of 0.953. Mean SPARC values differed between control and stroke subjects for the velopharynx (t = 3.25, p = 0.0058), tongue base (t = 4.77, p = 0.0003), and hypopharynx (t = 2.87, p = 0.0124). Values were similar for the UES (t = 0.43, p = 0.671).

Conclusions: In this preliminary study, SPARC analysis was applied to distinguish control from post-stroke subjects. Considering alternative methods of analyzing pharyngeal HRM data may provide additional insight into the pathophysiology of dysphagia beyond what can be gleaned from measures of pressure and duration alone.
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http://dx.doi.org/10.1111/nmo.14122DOI Listing
April 2021

The Influence of Voice Training on Vocal Learner's Objective Acoustic Voice Components.

J Voice 2021 Feb 27. Epub 2021 Feb 27.

Department of Voice, Xiamen University Zhongshan Hospital, Xiamen, Fujian, China. Electronic address:

Objective: Acoustic parameters of voice were studied in music majors throughout 18 months of training to understand the influence of voice training on voice.

Methods: Twenty-three students from Xiamen Music School between 12 and 15 years old were enrolled. Acoustic examination was performed three times- every 6 months for 18 months. Various traditional acoustic parameters were measured, including dysphonia severity index (DSI), jitter, and D-value of vocal range. Nonlinear dynamic measures were also measured, including diffusive chaos to construct voice type component profiles (VTCPs), spectrum convergence ratio, and nonlinear energy difference ratio. The results were analyzed by multivariate analysis of variance.

Results: Over the study duration, there was an improvement of DSI (P = 0.002), and D-value of vocal range (P = 0.000). Among nonlinear parameters, only voice type component data demonstrated significant changes during the study duration. Both Voice Type Component 1(VTC1) and VTC3 values differed from Time 1 to Time 2 as well as from Time 1 to Time 3. The proportion of VTC1 in samples generally decreased, while VTC3, representative of aperiodicity, increased. Both nonlinear energy difference ratio and spectrum convergence ratio exhibited no significant changes throughout the study.

Conclusion: Professional voice training can improve DSI and D-value of vocal range in singers' voices. These parameters have potential to be used for voice training evaluation and screening. Many nonlinear parameters did not detect differences in the healthy voices studied, but VTCPs created using intrinsic dimension present a valuable new method, visualizing increases in aperiodicity of the speaking voices after professional voice training.
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http://dx.doi.org/10.1016/j.jvoice.2021.01.011DOI Listing
February 2021

Age and Sex Comparison of Aerodynamic Phonation Measurements Using Noninvasive Assessment.

J Speech Lang Hear Res 2021 03 19;64(3):776-791. Epub 2021 Feb 19.

Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison.

Purpose The goal of this study was to present vocal aerodynamic measurements from pediatric and adult participant pools. There are a number of anatomical changes involving the larynx and vocal folds that occur as children age and become adults. Data were collected using two methods of noninvasive aerodynamic assessment: mechanical interruption and labial interruption. Method A total of 154 participants aged 4-24 years old took part in this study. Ten trials were performed for both methods of airway interruption. To perform mechanical interruption, participants phonated /α/ for 10 s trials while a balloon valve interrupted phonation 5 times. For labial interruption, participants said /pα/ 5 times at comfortable and quiet volumes. Aerodynamic measures included subglottal pressure, phonation threshold pressure, mean airflow, laryngeal resistance, and others. Results One hundred one participants (51 females) successfully completed testing with both methods. Eight out of 20 measurements were found to have a statistically significant effect of participant age on measurements. Sex alone had a significant effect on vocal efficiency for the labial quiet method. Conclusions The data discussed here can be used to view age and sex trends in vocal aerodynamic measurements. When using either method of mechanical or labial interruption, participant age needs to be taken into account to properly interpret several aerodynamic parameters. A participant's sex is not as important when using these methods.
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http://dx.doi.org/10.1044/2020_JSLHR-20-00501DOI Listing
March 2021

Laryngopharyngeal Reflux and Inflammatory Responses in Mucosal Barrier Dysfunction of the Upper Aerodigestive Tract.

J Inflamm Res 2020 5;13:1291-1304. Epub 2021 Jan 5.

Otorhinolaryngology Department, ENT Institute, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200032, People's Republic of China.

The upper aerodigestive tract (UAT) is the first line of defense against environmental stresses such as antigens, microbes, inhalants, foods, etc., and mucins, intracellular junctions, epithelial cells, and immune cells are the major constituents of this defensive mucosal barrier. Laryngopharyngeal reflux (LPR) is recognized as an independent risk factor for UAT mucosal disorders, and in this review, we describe the components and functions of the mucosal barrier and the results of LPR-induced mucosal inflammation in the UAT. We discuss the interactions between the refluxate and the mucosal components and the mechanisms through which these damaging events disrupt and alter the mucosal barriers. In addition, we discuss the dynamic alterations in the mucosal barrier that might be potential therapeutic targets for LPR-induced disorders.
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http://dx.doi.org/10.2147/JIR.S282809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801919PMC
January 2021

To Explore the Changes and Differences of Microstructure of Vocal Fold in Vocal Fold Paralysis and Cricoarytenoid Joint Dislocation by Diffusion Tensor Imaging.

J Voice 2020 Dec 31. Epub 2020 Dec 31.

Department of Voice, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, China. Electronic address:

Objective: The diffusion characteristics of water molecules were measured in the vocal folds of canines exhibiting unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation. These characteristics were used in conjunction with a histological examination of the microstructural changes of vocal fold muscle fibers to explore the feasibility of diffusion tensor imaging (DTI) in distinguishing unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation as well as evaluating microstructural changes.

Methods: Ten beagles were randomly divided into three groups: four in the unilateral vocal fold paralysis group, four in the unilateral cricoarytenoid joint dislocation group, and two in the normal group. Unilateral recurrent laryngeal nerve resection was performed in the vocal fold paralysis group. Unilateral cricoarytenoid joint dislocation surgery was performed in the dislocation group. No intervention was performed in the normal group. Four months postintervention, the larynges were excised and put into a magnetic resonance imaging (MRI) system (9.4T BioSpec MRI, Bruker, German) for scanning, followed by an analysis of diffusion parameters among the different groups for statistical significance. After MRI scanning, the vocal folds were cut into sections, stained with hematoxylin and eosin, and scanned digitally. The mean cross-sectional area of muscle fibers, and the mean diameter of muscle fibers in the vocal folds were calculated by target detection and extraction technology. Mean values of each measurement were used to compare the differences among the three groups. Pearson correlation analysis was performed on the DTI parameters and the results from histological section extraction.

Results: The paralysis group had significantly higher Fractional Anisotropy (FA) compared to the dislocation group and normal group (P = 0.004). The paralysis group also had a significantly lower Tensor Trace value compared to the dislocation group and normal group (P = 0.000). The average cross-sectional area of vocal fold muscle fibers in the paralysis group was significantly smaller than the dislocation group and normal group (P = 0.000). Pearson correlation analysis yielded values of, r = -0.785, P = 0.01 between the average cross-sectional area of vocal muscle fibers and FA, and values of r = 0.881, P = 0.00 between Tensor Trace and the average cross-sectional area of vocal muscle.

Conclusion: FA and Tensor Trace can be used as effective parameters to reflect the changes of microstructure in vocal fold paralysis and cricoarytenoid joint dislocation. DTI is an objective and quantitative method to effectively evaluate unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation, also capable of noninvasively evaluating vocal fold muscle fiber microstructure.
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http://dx.doi.org/10.1016/j.jvoice.2020.12.016DOI Listing
December 2020

Study of spatiotemporal liquid dynamics in a vibrating vocal fold by using a self-oscillating poroelastic model.

J Acoust Soc Am 2020 10;148(4):2161

Department of Surgery, Division of Otolaryngology - Head & Neck Surgery, University of Wisconsin Medical School of Medicine and Public Health, Madison, Wisconsin 53792-7375, USA.

The main purpose of this study is to investigate the spatiotemporal interstitial fluid dynamics in a vibrating vocal fold. A self-oscillating poroelastic model is proposed to study the liquid dynamics in the vibrating vocal folds by treating the vocal fold tissue as a transversally isotropic, fluid-saturated, porous material. Rich spatiotemporal liquid dynamics have been found. Specifically, in the vertical direction, the liquid is transported from the inferior side to the superior side due to the propagation of the mucosal wave. In the longitudinal direction, the liquid accumulates at the anterior-posterior midpoint. However, the contact between the two vocal folds forces the accumulated liquid out laterally in a very short time span. These findings could be helpful for exploring etiology of some laryngeal pathologies, optimizing laryngeal disease treatment, and understanding hemodynamics in the vocal folds.
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http://dx.doi.org/10.1121/10.0002163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575330PMC
October 2020

Simulation of Pediatric Endoscopic Cricoid Reduction and Expansion.

OTO Open 2020 Jul-Sep;4(3):2473974X20946268. Epub 2020 Jul 31.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.

Endoscopic cricoid expansion and reduction are newer approaches to the management of pediatric bilateral vocal fold immobility and postlaryngotracheal reconstruction glottic insufficiency, respectively. These procedures offer a less invasive, endoscopic alternative to procedures that typically required open management with a more prolonged recovery. These technically demanding procedures are currently performed only in select centers, and there is no currently described training model for practicing them. We present a modification to a laryngeal dissection station that allows for simulation of endoscopic cricoid reduction and expansion with excised larynges. The model allows trainees to practice endoscopic posterior cricoid exposure, incision of the cricoid cartilage, placement of a simulated costal cartilage graft for expansion, and endoscopic suturing for reduction. Development of simulators for procedures that are infrequently performed have the potential to help trainees reach surgical competency faster and more safely.
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http://dx.doi.org/10.1177/2473974X20946268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416139PMC
July 2020

Probability-Based Best Sample Selection for Acoustic Analysis of Normal and Disordered Voices.

J Voice 2020 May 29. Epub 2020 May 29.

University of Wisconsin-Madison School of Medicine and Public Health, Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Madison, Wisconsin. Electronic address:

Purpose: Acoustic analysis is a commonly used method for quantitatively measuring vocal fold function. The accuracy of acoustic analysis depends upon the operator selecting a stable segment of the voice sample to analyze. This paper proposes a novel method to more accurately and reliably select a stable voice segment.

Study Design: Four selection methods were implemented to evaluate each raw audio signal and determine the most stable segment of each signal: The proposed modal periodogram method, the moving window method, the midvowel method, and the whole vowel method. Acoustic parameters of interest-namely perturbation (jitter), correlation dimension (D2), and spectrum convergence ratio (SCR)-were calculated for 48 phonation samples to evaluate each method.

Methods: The proposed modal periodogram method utilizes a minimum mean-square error based approach to calculate a stable modal periodogram and obtain the most stable segment. The Wilcoxon Signed-Rank test was used to compare jitter, D2, and SCR values acquired using the modal periodogram method against the current standard segment selection methods.

Results: The modal periodogram method yielded significantly lower D2 values, and a significantly higher SCR for both normal and disordered voice samples (P < 0.01). This indicates that the modal periodogram method is more apt for selecting a stable audio segment than the other selection methods.
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http://dx.doi.org/10.1016/j.jvoice.2020.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704568PMC
May 2020

Retest Reliability for Complete Airway Interruption Systems of Aerodynamic Measurement.

J Voice 2020 Apr 3. Epub 2020 Apr 3.

University of Wisconsin School of Medicine and Public Health, Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Madison, Wisconsin. Electronic address:

Introduction: Measures of subglottal pressure (Ps), phonation threshold pressure (PTP), and laryngeal resistance (LR) can be used as indicators of vocal cord disorders. The gold standard non-invasive measurement uses labial interruption, which has been shown to have reliability inconsistencies. Mechanical interruption methods have demonstrated promise in measurement reliability. The goal of the present study is to compare retest reliability of labial and mechanical interruption methods.

Methods: 55 subjects aged 18-69 participated. Ten trials were performed for each method. For labial interruption, subjects produced five labial plosives at comfortable and quiet volumes. For mechanical interruption, subjects produced a sustained /α/ while a balloon valve interrupted phonation five times. Thirty subjects completed a second study visit identical to the first approximately two weeks (15 days ± 3.76) after the first visit. Ps, PTP, mean airflow rate, and LR were determined for each subject and retest reliability for each was analyzed.

Results: The percent difference in measurement results for test-retest of Ps were 12.88% ± 10.15 for mechanical interruption and 27.56% ± 17.14 for labial interruption (P = 0.0003). The percent difference for PTP measurements were 21.46% ± 16.01 for mechanical and 17.04% ± 14.62 (P = 0.3372) for labial. Intra-subject coefficients of variation of Ps were 0.086 ± 0.046 for mechanical and 0.161 ± 0.078 for labial (P < 0.0001). For PTP, the coefficients were 0.177 ± 0.083 for mechanical and 0.186 ± 0.091 for labial (P = 0.5402). Lastly, for LR (Ps divided by mean airflow rate) the percent differences were 14.33% ± 10.06 for mechanical and 53.87% ± 43.19 for labial (P < 0.0001) with intra-subject variability of 0.115 ± 0.050 for mechanical and 0.287 ± 0.222 for labial (P < 0.0001).

Conclusions: Ps and LR measured using mechanical interruption showed more consistency for both retesting across separate study visits and intra-subject variability. PTP was similar in retesting and intra-subject variability. Continued work to improve mechanical interruption techniques is warranted as these methods offer higher reliability and consistency than the labial interruption methods.
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http://dx.doi.org/10.1016/j.jvoice.2020.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541393PMC
April 2020

The Therapeutic Effects of Straw Phonation on Vocal Fatigue.

Laryngoscope 2020 11 23;130(11):E674-E679. Epub 2020 Jan 23.

Department of Otolaryngology-Head and Neck Surgery, Eye and Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Objectives: Straw phonation has been investigated for its vocal warm-up effects on healthy populations and therapeutic effects on voice patients. The purpose of this article was to determine whether it is beneficial for vocal fatigue.

Study Design: Prospective cohort study METHODS: Twenty-five healthy participants were recruited into 1-hour vocal loading tasks followed by 10-minute vocal rest or straw phonation on 2 different days. Various parameters including phonation threshold pressure (PTP), mean airflow, closed quotient (CQ), current speaking effort level (EFFT), and laryngeal discomfort (DISC) were acquired at baseline, after vocal load, and after the intervention.

Results: Increased PTP, EFFT, and DISC were observed after vocal load. Decreased PTP, EFFT, and DISC were then acquired after both vocal rest or straw phonation. More significant improvements were obtained in straw phonation when compared with vocal rest. Additionally, significantly increased mean flow and decreased CQ were obtained after straw phonation when compared to vocal rest.

Conclusions: Straw phonation has the potential to adjust aerodynamics within the vocal tract leading to improved vocal efficiency, optimized vibration mode, and attenuated vocal fatigue. This study provided a promising treatment for vocal fatigue that could have wide clinical relevance to voice users with high voice demands.

Level Of Evidence: 4 Laryngoscope, 130:E674-E679, 2020.
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http://dx.doi.org/10.1002/lary.28498DOI Listing
November 2020

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

Laryngoscope 2020 11 24;130(11):E646-E653. Epub 2019 Dec 24.

Department of Physics, Xiamen University, Xiamen, Fujian, China.

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.
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http://dx.doi.org/10.1002/lary.28468DOI Listing
November 2020

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

J Voice 2021 Mar 22;35(2):328.e23-328.e28. Epub 2019 Oct 22.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.

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 χ 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.
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http://dx.doi.org/10.1016/j.jvoice.2019.09.010DOI Listing
March 2021

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

Ear Nose Throat J 2021 May 24;100(4):NP177-NP184. Epub 2019 Sep 24.

Department of ENT, Zhongshan Hospital, 12466Xiamen University, Xiamen, China.

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, < .05. In the lamina propria, the FA of the unilateral RLN injury group was lower than that of the control group, > .05, and the Tensor Trace was lower than that of the control group, < .05. The muscle fiber cross-sectional area of the RLN injury group was significantly smaller than the control group with statistical significance, < .05, and the density of muscle fibers was lower, < .05. The correlation coefficient between FA and the cross-sectional area was -0.838, = .002, and .726; = .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.
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http://dx.doi.org/10.1177/0145561319874721DOI Listing
May 2021

Dynamically Monitoring Vocal Fatigue and Recovery Using Aerodynamic, Acoustic, and Subjective Self-Rating Measurements.

J Voice 2019 Sep 29;33(5):809.e11-809.e18. Epub 2018 Jun 29.

Department of Otolaryngology-Head and Neck Surgery, EENT Hospital of Fudan University, Shanghai, China. Electronic address:

Objectives: This study aimed to quantify the effects of vocal loading and vocal rest using aerodynamic, acoustic, and self-rating measurements.

Methods: Ten participants were recruited to perform vocal loading tasks lasting 60 minutes, followed by 30 minutes of vocal rest. Objective parameters (phonation threshold pressure, fundamental frequency, jitter, shimmer, and noise-to-harmonics ratio) and subjective parameters (current speaking effort level and laryngeal discomfort) were taken at different time intervals: before vocal loading (baseline), after 15 minutes (L15), 30 minutes (L30), 45 minutes (L45), and 60 minutes (L60) of vocal loading, as well as after 5 minutes (R5), 10 minutes (R10), 20 minutes (R20), and 30 minutes (R30) of vocal rest.

Results: Phonation threshold pressure was found to increase significantly within the first 15 minutes of the vocal loading task (P = 0.032), followed by a relatively gentle increase in the subsequent 45 minutes. Subjective self-ratings increased significantly after 30 minutes of loud reading (P < 0.05). Phonation threshold pressure recovered faster than subjective parameters after the vocal loading activity had finished. Fundamental frequency was found to consistently increase during vocal loading but return to baseline rapidly within 5 minutes of vocal rest. However, no significant changes in jitter, shimmer, and noise-to-harmonics ratio were observed after vocal loading.

Conclusions: Phonation threshold pressure and self-ratings may have the potential to track vocal fatigue and recovery. Furthermore, a dynamic monitor of vocal fatigue was presented, which may further provide a guide for appropriate voice use.
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http://dx.doi.org/10.1016/j.jvoice.2018.03.014DOI Listing
September 2019

The Effects of Photobiomodulation on Vocal Fold Wound Healing: and Studies.

Photobiomodul Photomed Laser Surg 2019 Sep;37(9):532-538

The Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Photobiomodulation (PBM) is increasingly used in dermatology and dentistry due to its benefit of promoting wound healing and relieving pain; however, there is no corresponding research report on the application of PBM to vocal fold wound healing. To assess the potential wound-healing effects of PBM on the vocal folds via and experiments. In study, vocal fold fibroblasts (VFFs) were irradiated under a diode laser with wavelength of 635 nm at energy density of 8 J/cm. The Cell Counting Kit-8 (CCK-8) assay was used to study the viability of VFFs, and the gene expressions of , , , , and were investigated by real-time polymerase chain reaction (RT-PCR). In study, 15 rabbits were used. Lamina propria of the left vocal folds of 12 rabbits was unilaterally stripped, and 6 of them were treated with PBM. The remaining three rabbits served as normal controls. After 3 months, all animals were sacrificed to obtain histological results. We used laryngoscope to record images of the healing phase. Irradiation with energy density of 8 J/cm resulted in a 2.8% increase in cell proliferation ( < 0.05). However, the difference between the experimental and the control group became larger after 48 and 72 h of subsequent irradiation. RT-PCR results showed that the expression of , , and was higher, and the expression of and was lower. Histological examination showed that, compared with the injury group, hyaluronic acid (HA) increased significantly, collagen deposition decreased, and the configuration of collagen was more organized after PBM treatment. PBM can inhibit inflammatory reaction and promote the secretion of HA to decrease the deposition of collagen and regenerate vocal fold tissue without scar.
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http://dx.doi.org/10.1089/photob.2019.4641DOI Listing
September 2019

Effects of Varying Lengths and Diameters During Straw Phonation on an Excised Canine Model.

J Voice 2021 Jan 25;35(1):85-93. Epub 2019 Jul 25.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address:

Objective/background: Straw phonation, a well-established method of vocal exercise, started over 100 years ago. However, some of the most basic questions about best practices remain including the ideal extension length and the ideal restriction (semiocclusion) diameter. This study aims to help answer these questions by looking at both separately, with all other variables controlled.

Methods: Four (4) straws with lengths of 5, 25, 50, and 75 centimeters and 4 restrictions with diameters of 3, 9, 15, and 21 mm were tested, separately. They were attached to the end of a simulated vocal tract which was then affixed to an excised canine larynx. Airflow was increased until the larynges achieved self-sustained phonation then aerodynamic, acoustic, and electroglottographic data were collected.

Results: There was a significant decrease in the phonation threshold pressure using the 5 and 25 cm straw lengths and the 9 and 15 mm restrictions. The phonation threshold flow and contact quotient saw insignificant changes, except in the case of the 3 mm restriction.

Discussion: It is theorized that the increased inertive reactance helps to decrease phonation threshold pressure. By controlling for all other variables, the effects of the length or diameter of the straw can be analyzed in isolation. These results narrow the significant range of lengths and diameters used in straw phonation.
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http://dx.doi.org/10.1016/j.jvoice.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981038PMC
January 2021

Measurement Reliability of Laryngeal Resistance and Mean Flow Rate in Pediatric Subjects.

J Voice 2020 Jul 19;34(4):590-597. Epub 2019 Feb 19.

University of Wisconsin School of Medicine and Public Health, Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Madison, Wisconsin. Electronic address:

Objective: Mean flow rate (MFR) and laryngeal resistance (R) are sensitive to changes in glottal configuration and biomechanics. There is little reported on aerodynamic parameters in children. We conducted a pilot study to evaluate MFR and R measurement reliability in a pediatric population using labial and mechanical interruption methods.

Method: Thirty-nine subjects aged 4-17 performed 10 trials per method. For labial interruptions, subjects produced five labial plosives at a comfortable amplitude. For mechanical interruptions, subjects maintained a steady /α/ while a balloon valve interrupted their airflow five times for 250 milliseconds each. MFR was measured as the flow through the interruption device between interruptions. R was calculated by dividing subglottal pressure (P) by MFR. The primary outcome measures of this study were the coefficients of variation of MFR and R. Paired t tests were used to compare each variable between the two methods. Pearson's correlation was used to analyze the relationship between each parameter and subject age.

Results: Mean P (t(38) = 2.966, P < 0.01) and R (t(38)=3.563, P < 0.01) were higher for labial interruptions while mean MFR (t(38) = -2.036, P < 0.05) was lower. Intrasubject coefficients of variation were higher for the labial technique for both MFR (t(38) = 4.939, P < 0.001) and R (t(38) = 3.439, P < 0.01) while there was no difference in P variability (P = 0.260). Mean MFR and R were related to age for both the labial (MFR: r = 0.588, P < 0.001; R: r = -0.468, p = 0.003) and mechanical trials (MFR: r = 0.534, P < 0.001; R: r = -0.496, P = 0.001). The coefficients of variation for R were negatively correlated with age for both labial (r = -0.415, P = 0.009) and mechanical trials (r = -0.471, P = 0.002). MFR was only correlated in the labial trials (r = -0.514, P = 0.001) and P was only correlated in the mechanical trials (r = -0.519, P = 0.001).

Conclusions: Differences in means and intrasubject variation are likely due to differences in task and measurement timing. Precision of MFR and R measurement in pediatric subjects was higher for mechanical interruption; further exploration of this method and its clinical utility is warranted. Measurement of aerodynamic parameters may be a useful addition to pediatric voice assessment.
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http://dx.doi.org/10.1016/j.jvoice.2019.02.005DOI Listing
July 2020

Effects of a simulated system of straw phonation on the complete phonatory range of excised canine larynges.

Eur Arch Otorhinolaryngol 2019 Feb 10;276(2):473-482. Epub 2019 Jan 10.

Department of Otolaryngology-Head and Neck Surgery, EENT Hospital of Fudan University, Shanghai, 200031, China.

Purpose: This study investigated the effects of straw phonation therapy on the aerodynamic and acoustic parameters of the vocal folds at different levels of elongation and subglottal pressure.

Methods: 20 excised canine larynges were used in both experimental (straw phonation therapy simulation) and control conditions. Aerodynamic parameters, including phonation threshold pressure (PTP), phonation instability pressure (PIP), phonation pressure range (PPR), phonation threshold flow (PTF), phonation instability flow (PIF), phonation flow range (PFR), were obtained at different levels of vocal fold elongation (0%, 10%, 20%). Acoustic parameters, including fundamental frequency (F0), jitter, shimmer, signal noise ratio (SNR) were detected at different levels of vocal fold elongation (0%, 10%, 20%) and subglottal pressure (15 cmHO, 20 cmHO, 25 cmHO).

Results: Significant decreases in PTP and PTF and significant increases in PIP, PIF, PPR, and PFR occurred in experimental condition at all levels of elongation when compared with control condition. However, no significant changes of acoustic parameters were obtained between conditions at all levels.

Conclusion: At different levels of vocal fold elongation, straw phonation not only lowered the onset of normal voice, but also elevated the onset of chaotic voice, indicating a better voice economy and voice control. Moreover, the improved phonatory range demonstrated that straw phonation had the potential to prevent voice users who have high voice demand from voice fatigue and vocal damage.
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http://dx.doi.org/10.1007/s00405-018-5247-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541208PMC
February 2019

Quantitative second harmonic generation imaging of leporine, canine, and porcine vocal fold collagen.

Laryngoscope 2019 11 9;129(11):2549-2556. Epub 2019 Jan 9.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A.

Objectives/hypothesis: Vocal fold collagen composition is an important determinant of material properties and mucosal wave propagation. Collagen alignment and straightness are quantitatively characterized by second harmonic generation (SHG) imaging. We examined leporine, canined and porcine vocal folds showing collagen composition variation that is species, location, and strain specific.

Study Design: Animal model.

Methods: Leporine (n = 5), canine (n = 5), and porcine (n = 5) larynges were harvested and fixed in situ. Samples were transversely sectioned, and SHG images were collected for two inferior-superior sections along five anterior-posterior locations. Additional porcine samples were fixed and imaged under tensile strain (0%, 5%, 10%, 15%, 20%, n = 5 per group). Two-way repeated measures (RM) analysis of variance (ANOVA) tested for section and location differences in each species. Multiway RM-ANOVA tested for section, location, and strain differences in porcine samples.

Results: Alignment and straightness were higher inferiorly in the porcine (P = .0047, P = .002) and canine (P = .0011, P < .001) vocal folds, but not in leporine samples (P = .67652, P = .4831). There were significant interactions between elongation and superior-inferior section for both alignment (P = .0047) and straightness (P = .0371).

Conclusions: Our results correspond well to findings in the literature that the inferior vocal fold lip is stiffer in porcine and canine larynges. The absence of a collagen gradient in the leporine vocal fold is notable because rabbits are less vocal animals, indicating the collagen gradient may be a result of voice use and an important consideration in model selection when extracellular matrix is of interest. Strain results were also consistent with the role of collagen in strain stiffening behavior of vocal fold tissue.

Level Of Evidence: NA Laryngoscope, 129:2549-2556, 2019.
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http://dx.doi.org/10.1002/lary.27782DOI Listing
November 2019

Establishment of a novel and effective reflux laryngitis model in rabbits: a preliminary study.

Eur Arch Otorhinolaryngol 2019 Jan 10;276(1):175-183. Epub 2018 Dec 10.

The Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200030, China.

Purpose: To establish a novel and effective reflux model with a modified nasogastric aspiration tube and to investigate the association between different types of nasogastric aspiration tubes and reflux laryngitis, we conducted this study.

Methods: Thirty-eight healthy New Zealand albino rabbits (2.5-3.5 kg) were divided into three groups: control (CTR, n = 6)-non-intubated; normal nasogastric intubation (NNI, n = 16)-intubated with 4#, 6#, 8#, and 10# normal nasogastric aspiration tubes; and modified nasogastric intubation (MNI, n = 16)-intubated with 4#, 6#, 8#, and 10# modified nasogastric aspiration tubes. The laryngoscopy, body weight, and pH values at the esophageal entrance were recorded before and 1, 2, and 4 weeks after intubation. After the final laryngoscopy, the animals in groups with a pH below 4 were sacrificed to obtain histological and gene expression analysis results.

Results: The reflux finding score (RFS) after 4 weeks showed that there was a statistically significant difference in the 8# NNI group (7 ± 0.816, P < 0.001), the 8# MNI group (11.5 ± 2.517, P < 0.001) and the 10# MNI (12.75 ± 1.893, P < 0.001) group compared with the control group (1.83 ± 1.602). The pH values of these three groups were lower than 4. However, the weight loss of the rabbits in the 10# NNI and 10# MNI groups was more obvious. Submucous gland hyperplasia and inflammation were significantly increased in the 8# NNI group, 8# MNI group and the 10# MNI group, but in the level of some pro-inflammatory cytokines and COX-2, the MNI group was significantly higher than the NNI group (8# NNI × 8# MNI, P < 0.01; 8# MNI × 10# MNI, P < 0.01).

Conclusion: This study showed that 8# modified nasogastric intubation (MNI) produces effective reflux laryngitis in the rabbits.
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http://dx.doi.org/10.1007/s00405-018-5234-7DOI Listing
January 2019

The effects of cryotherapy on vocal fold healing in a rabbit model.

Laryngoscope 2019 04 23;129(4):E151-E157. Epub 2018 Nov 23.

Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Objectives/hypothesis: Cryotherapy has been shown to be a scarless treatment modality for dermal lesions; however, there are limited data addressing the effect of cryotherapy on vocal fold tissue. The aim of this study was to clarify the effectiveness of cryotherapy for prevention of postsurgical vocal fold scarring.

Study Design: Prospective animal study in rabbits.

Methods: The lamina propria of 20 rabbit vocal folds was bilaterally stripped, followed by randomized unilateral cryotherapy. Five larynges were harvested for real-time polymerase chain reaction (RT-PCR) analysis at 1 day, 3 days, and 7 days postinjury. The remaining five were harvested for histologic analysis at 3 months. Images of the healing phase were recorded by laryngoscopy. Analyses of RT-PCR for cyclooxygenase (COX)-2, interleukin (IL)-6, collagen I, collagen III, matrix metallopeptidase 1 (MMP1), transforming growth factor β (TGFβ1), α smooth muscle actin (α-SMA), and hyaluronan synthase 1 (HAS1) were completed. Histological samples were completed for collagen and hyaluronic acid analysis.

Results: RT-PCR results revealed that higher expressions of HAS1 and MMP1 and lower expressions of COX-2, IL-6, collagen I, collagen III, TGFβ1, and α-SMA were observed, and histological examination showed significantly increased hyaluronic acid, decreased deposition, and more organized configuration of collagen in injury with the cryotherapy cohort compared with the injury cohort.

Conclusions: Cryotherapy can inhibit the inflammatory reaction and simulate a fetal healing environment in extracellular matrix synthesis to regenerate vocal fold tissue with less fibrosis. Histological results showed that cryotherapy achieves a mature healing result with less scar, which tends to return to normal. In summary, the findings of this study suggest that administration of cryotherapy at the time of injury has the potential to minimize vocal fold scarring.

Level Of Evidence: NA Laryngoscope, 129:E151-E157, 2019.
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http://dx.doi.org/10.1002/lary.27629DOI Listing
April 2019

Topical Application of 5-Aminolevulinic Acid Is Sufficient for Photodynamic Therapy on Vocal Folds.

Laryngoscope 2019 02 8;129(2):E80-E86. Epub 2018 Nov 8.

Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Objectives: To evaluate the feasibility of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) for vocal fold leukoplakia.

Study Design: Ex vivo and in vivo.

Methods: 5-ALA was applied topically as a 20% solution to ex vivo canine vocal folds. The penetration depth and concentrations of 5-ALA in tissue were quantified using frozen sectioning and fluorescamine derivatization after 5-ALA contact incubation or topical spraying. Then, 5-ALA solution was sprayed on leporine vocal folds once, twice, or given systemically in vivo. Protoporphyrin IX (PPIX) location was visualized using fluorescence microscopy, and PPIX concentrations were measured using a fluorescent quantitative method. Hematoxylin and eosin (H&E) staining was performed to visualize the histological changes of vocal folds after PDT for each group.

Results: Topical incubation of 15 minutes with 5-ALA achieved a penetration depth of over 2 mm and similar concentrations within the superficial 500 μm of epithelium, compared with longer incubation times. Topical spraying of 5-ALA produced sufficient concentrations in vocal folds, but the retention time is short. An in vivo leporine model showed that laryngeal spraying of 20% 5-ALA induced similar penetration depth and concentrations of PPIX compared to systemic administration of 5-ALA. Two sprays of 20% 5-ALA solution with an interval of 30 minutes are needed to produce complete exfoliation of vocal fold epithelium.

Conclusion: Topical PDT with laryngeal spraying of 20% 5-ALA solution achieves sufficient therapeutic effects and is potentially applicable for the treatment of vocal fold leukoplakia.

Level Of Evidence: NA Laryngoscope, 129:E80-E86, 2019.
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http://dx.doi.org/10.1002/lary.27437DOI Listing
February 2019

Measurement reliability of phonation threshold pressure in pediatric subjects.

Laryngoscope 2019 07 8;129(7):1520-1526. Epub 2018 Nov 8.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A.

Objectives/hypothesis: Phonation threshold pressure (PTP), the minimum subglottal pressure (P ) required for phonation, is sensitive to changes in laryngeal biomechanics and is often elevated with pathology. Little is reported on PTP in children; challenges with task performance and measurement reliability represent barriers to routine clinical assessment.

Study Design: Pilot study evaluating PTP and P measurement reliability in children using labial and mechanical interruption.

Methods: Twenty-two subjects aged 4 to 17 years (10.7 ± 3.9 years) participated. Ten trials were performed for each method; task order was randomized. For labial interruption, subjects produced /pα/ five times at softest (onset PTP) and comfortable amplitude. For mechanical interruption, subjects produced a sustained /α/ while a balloon valve interrupted phonation five times for 250 ms each; mechanical interruption was performed with a mouthpiece and mask. PTP was recorded as the difference between P and supraglottal pressure at phonation cessation (offset PTP). Mean PTP and P and intrasubject coefficients of variation were compared. Correlations with age were evaluated.

Results: Mean PTP (P < .001) and P (P = .005) were higher for labial interruption. Intrasubject coefficients of variation for PTP (P = .554) and P (P = .305) were similar across methods. Coefficient of variation was related to age for mechanical-mask trials only (r = -0.628, P = .00175).

Conclusions: Differences in means are likely related to differences in task and PTP hysteresis effect. Reliability is comparable with all methods; using a mouthpiece may be preferable to a mask for mechanical interruption. Measurement of PTP is noninvasive, reliable, and may be a useful adjunct in pediatric voice assessment.

Level Of Evidence: 3b Laryngoscope, 129:1520-1526, 2019.
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http://dx.doi.org/10.1002/lary.27418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506412PMC
July 2019

Cryotherapy has antifibrotic and regenerative effects on human vocal fold fibroblasts.

Laryngoscope 2019 04 12;129(4):E143-E150. Epub 2018 Oct 12.

Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Objectives/hypothesis: Vocal fold scarring remains a major treatment challenge, and scar prevention without residual lesions remains a dilemma. Cryotherapy has shown cosmetic outcomes on skin lesions with minimal scarring. The aim of this study was to clarify the beneficial effects of cryotherapy for the prevention and the treatment of vocal fold scarring.

Study Design: In vitro.

Methods: Primary cultures of human vocal fold fibroblasts (VFFs) were used in this study. Myofibroblast differentiation was stimulated by transforming growth factor β1 (TGF-β1). We mimicked the cryotherapy effect on vocal fold healing in vivo by freezing VFFs ± TGF-β1 in vitro. The influence of freezing on cell viability, proliferation, migration, and contractile properties were analyzed. The expression of collagen I, collagen III, fibronectin, TGF-β1, matrix metallopeptidase 1 (MMP1), hyaluronan synthase 1 (HAS1) were investigated by real-time polymerase chain reaction (RT-PCR), and the expression of alpha smooth muscle actin (α-SMA) and decorin were investigated by RT-PCR and Western blot.

Results: Freezing was found to modify extracellular matrix (ECM) synthesis and differentiation of VFFs. Expression of collagen I, collagen III, fibronectin, α-SMA, and TGF-β1 was downregulated, and MMP1 was upregulated in VFFs + TGF-β1 (myofibroblast) by freezing. HAS1 and decorin were upregulated in both VFFs ± TGF-β1 by freezing. Freezing VFFs + TGF-β1 (myofibroblast) with fast thawing had a lower expression of α-SMA when compared with slow thawing. Freezing reduced the migration and collagen contraction of VFFs + TGF-β1 (myofibroblast).

Conclusion: Cryotherapy induces antifibrotic and regenerative ECM alterations in VFFs. These data provide insight into the prevention and the treatment of vocal fold scarring with cryotherapy in phonomicrosurgery.

Level Of Evidence: NA Laryngoscope, 129:E143-E150, 2019.
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http://dx.doi.org/10.1002/lary.27499DOI Listing
April 2019

Development of Excised Larynx.

J Voice 2020 Jan 24;34(1):38-43. Epub 2018 Sep 24.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; University of Wisconsin-Madison, School of Medicine and Public Health, Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Madison, Wisconsin. Electronic address:

The larynx is a complex organ which has a role in a variety of functions such as phonation, breathing, and swallowing. To research these functions, it is widely accepted that in vivo studies provide more anatomically and physiologically relevant findings. However, invasive procedures are generally needed to measure variables such a subglottal pressure, vocal fold tension and stiffness, and cricothyroid muscle stretch. Performing studies using excised larynges is a useful technique which makes it possible to not only measure phonation parameters but control them as well. Early studies using excised larynges mainly focused on controlling specific parameters and mathematical modeling simulations. The use of these studies has helped further research in laryngeal anatomy, imaging techniques, as well as aerodynamic, acoustic, and biomechanical properties. Here, we describe the progress of this research over the past 5 years. The number of accepted animal models has increased and ideas from excised larynx studies are starting to be applied to treatment methods for laryngeal disorders. These experiments are only valid for an excised situation and must continue to be combined with animal experimentation and clinical observations.
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http://dx.doi.org/10.1016/j.jvoice.2018.07.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431582PMC
January 2020

Wound-healing effects of 635-nm low-level laser therapy on primary human vocal fold epithelial cells: an in vitro study.

Lasers Med Sci 2019 Apr 22;34(3):547-554. Epub 2018 Sep 22.

The Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200030, China.

Low-level laser therapy (LLLT) has been promoted for its beneficial effects on tissue healing and pain relief for skin and oral applications. However, there is no corresponding literature reporting on vocal fold wound healing. Our purpose was to assess the potential wound-healing effects of LLLT on primary human vocal fold epithelial cells (VFECs). In this study, normal vocal fold tissue was obtained from a 58-year-old male patient who was diagnosed with postcricoid carcinoma without involvement of the vocal folds and underwent total laryngectomy. Primary VFECs were then cultured. Cells were irradiated at a wavelength of 635 nm with fluences of 1, 4, 8, 12, 16, and 20 J/cm (50 mW/cm), which correspond to irradiation times of 20, 80, 160, 240, 320, and 400 s, respectively. Cell viability of VFECs in response to varying doses of LLLT was investigated by the Cell Counting Kit-8 (CCK-8) method. The most effective irradiation dose was selected to evaluate the cell migration capacity by using the scratch wound-healing assay. Real-time polymerase chain reaction (RT-PCR) was used to detect the gene expression of TGF-β1, TGF-β3, EGF, IL-6, and IL-10. Irradiation with doses of 8 J/cm resulted in 4% increases in cell proliferation differing significantly from the control group (p < 0.05). With subsequent doses at 48 and 72 h after irradiation, the differences between the experimental and the control groups became greater, up to 9.8% (p < 0.001) and 19.5% (p < 0.001), respectively. It also increased cell migration and the expression of some genes, such as EGF, TGF-β1, TGF-β3, and IL-10, involved in the tissue healing process. This study concludes that LLLT at the preset parameters was capable of stimulating the proliferation and migration of human vocal fold epithelial cells in culture as well as increase the expression of some genes involved in tissue healing process. Additionally, successive laser treatments at 24 h intervals have an additive beneficial effect on the healing of injured tissues.
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http://dx.doi.org/10.1007/s10103-018-2628-0DOI Listing
April 2019

Study on Normal Laryngeal Electromyography of Thyroarytenoid Muscle, Cricothyroid Muscle, and Posterior Cricoarytenoid Muscle.

Ann Otol Rhinol Laryngol 2018 Nov 6;127(11):806-811. Epub 2018 Sep 6.

2 Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.

Objective: The aim of this study was to investigate the physiological activity of intrinsic laryngeal muscle under different functional states of larynx by measuring the normal laryngeal electromyography parameters.

Methods: Laryngeal electromyography (EMG) was performed in 112 patients with unilateral vocal cord movement disorder. The duration and amplitude of the motor unit potential (MUP) of the thyroarytenoid muscle (TA), posterior cricoarytenoid muscle (PCA), and cricothyroid muscle (CT) were measured when patients were asked to make a deep inspiration and phonate /i/. The normal side of the patients' vocal chords was used as the research object.

Results: (1) The motor unit potential of TA, CT, and PCA were measured when inspiration and phonating /i/. Waveforms were normal. (2) There were significant differences in duration of TA between inspiration and phonating /i/ in comfortable tone. (3) When comparing the duration and amplitude of any 2 of TA, CT, and PCA during inspiration and phonating /i/, there were significant differences in duration between CT and PCA when phonating /i/ only. There were no significant differences in any other comparisons.

Conclusions: Under either deep inspiration or pronunciation, the TA, CT, and PCA muscles were activated. The TA may play a major role in phonating. The PCA may play a major role in the action of deep inspiration.
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http://dx.doi.org/10.1177/0003489418796525DOI Listing
November 2018

Quantitative Measurement of the Three-dimensional Structure of the Vocal Folds and Its Application in Identifying the Type of Cricoarytenoid Joint Dislocation.

J Voice 2019 Sep 23;33(5):611-619. Epub 2018 Aug 23.

Division of Otolaryngology, Xiamen University Zhongshan Hospital, Xiamen, Fujian, China. Electronic address:

Objective: The objective of this study was to quantitatively measure the three-dimensional (3D) structure of the vocal folds in normal subjects and in patients with different types of cricoarytenoid dislocation. We will analyze differences in parameters between the groups and also determine if any morphologic parameters possess utility in distinguishing the type and the degree of cricoarytenoid dislocation.

Study Design: This retrospective study was conducted using university hospital data.

Methods: Subjects' larynges were scanned using dual-source computed tomography (CT). The normal subjects were divided into deep-inhalation and phonation groups, and patients with cricoarytenoid joint dislocation were divided into anterior-dislocation and posterior-dislocation groups. Membranous vocal fold length and width were measured directly on the thin-section CT images. Vocal fold and airway 3D models were constructed using Mimics software and used in combination to measure vocal fold thickness, subglottal convergence angle, and oblique angle of the vocal folds.

Results: The phonation group displayed a greater vocal fold width, greater oblique angle, thinner vocal folds, and a smaller subglottal convergence angle than those of the deep-inhalation group (P < 0.05). The anterior-dislocation group displayed a smaller oblique angle and subglottal convergence angle than the posterior-dislocation group (P < 0.05).

Conclusions: The 3D structure of the vocal folds during deep inhalation and phonation can be accurately measured using dual-source CT and laryngeal 3D reconstruction. As the anterior-dislocation group yielded negative values for the oblique angle and the posterior-dislocation group yielded positive values, the oblique angle of the vocal folds may possess utility for distinguishing the type and for quantitatively determining the degree of cricoarytenoid dislocation.
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http://dx.doi.org/10.1016/j.jvoice.2018.02.024DOI Listing
September 2019
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