Bio


Dr. Ted Mau is a board-certified, fellowship-trained laryngologist with Stanford Health Care Ear, Nose, and Throat. He is also a professor in the Department of Otolaryngology – Head & Neck Surgery and chief of the Division of Laryngology at Stanford University School of Medicine. Dr. Mau came to Stanford in 2025 following 17 years at the University of Texas Southwestern Medical Center in Dallas, Texas, where he was director of the Voice Center and vice chair of research for the Department of Otolaryngology – Head and Neck Surgery.

Dr. Mau’s clinical practice focuses on disorders of the voice, airway, and swallowing. He has particular interest in vocal fold and laryngeal lesions, voice problems, vocal fold paralysis, recurrent laryngeal nerve injuries, and laryngeal dystonia. He is an expert in microlaryngeal surgeries, including laser surgeries of the larynx and airway. He also has extensive experience with laryngeal framework surgery for the treatment of vocal fold paralysis, as well as in-office procedures for vocal fold and larynx lesions.

As a physician-scientist, Dr. Mau engages in clinical and laboratory research in voice science and voice disorders. He has served as principal investigator or co-investigator on several National Institutes of Health (NIH)-funded projects, including computational voice simulation, development of ultrafast laser microlaryngeal surgery, sensory contributions to voice disorders, and central neuromodulation as a treatment for recurrent laryngeal nerve injuries. Dr. Mau was a site investigator for a DNA therapeutic vaccine clinical trial for recurrent respiratory papillomatosis. He has served on several NIH study sections.

Dr. Mau served as associate editor of laryngology for The Laryngoscope, a leading journal in the field of otolaryngology. He has published articles in peer-reviewed journals such as the Journal of Voice, The Laryngoscope, and Otolaryngology – Head and Neck Surgery.

Dr. Mau is a fellow of the American Laryngological Association (ALA) and the Triological Society. He is also a member of the American Broncho-Esophagological Association and the secretary of the ALA Council.

Clinical Focus


  • Otolaryngology

Academic Appointments


  • Professor - University Medical Line, Otolaryngology (Head and Neck Surgery)

Administrative Appointments


  • Chief, Division of Laryngology (2025 - Present), Department of Otolaryngology, Stanford University School of Medicine (2025 - Present)
  • Professor - University Medical Line, Otolaryngology (Head and Neck Surgery), Stanford University School of Medicine (2025 - Present)

Honors & Awards


  • Phi Beta Kappa, Harvard College (1990)
  • Distinction in Teaching, Department of Mathematics, Harvard University (1991)
  • Henderson Prize for Outstanding Undergraduate Thesis in Biochemical Sciences, Harvard University (1992)
  • Howard Hughes Medical Institute Predoctoral Fellowship, University of California, San Francisco (1992-1997)
  • Young Faculty/Practitioner Award, American Laryngological Association (2010)
  • Honor Award, American Academy of Otolaryngology – Head and Neck Surgery (2016)
  • Casselberry Award, American Laryngological Association (2017)
  • Steven D. Gray Memorial Endowed Lectureship in Otolaryngology, University of Utah (2017)
  • Casselberry Award, American Laryngological Association (2021)
  • Honor Award, American Academy of Otolaryngology – Head and Neck Surgery (2021)
  • H. Bryan Neel, III, MD, PhD Lectureship in Otolaryngology, Mayo Clinic (2024)

Boards, Advisory Committees, Professional Organizations


  • Chair, Research Committee, American Laryngological Association (2017 - 2023)
  • Member, Nominating Committee, American Laryngological Association (2016 - 2017)
  • Member, Casselberry Award Committee, American Laryngological Association (2021 - 2024)
  • Member, Voice Committee, American Academy of Otolaryngology-Head and Neck Surgery (2009 - 2015)
  • Member, American Broncho-Esophagological Association (2011 - Present)
  • Fellow, Triological Society (2012 - Present)
  • Fellow, American Laryngological Association (2015 - Present)
  • Member, Research Grants Committee, American Laryngological Association (2015 - Present)
  • Editorial Board, Journal of Voice (2016 - Present)
  • Member, NIH/CSR Motor Function, Speech and Rehabilitation Study Section (2020 - 2024)
  • Associate Editor, The Laryngoscope (2020 - 2024)
  • Council, American Laryngological Association (2024 - Present)

Professional Education


  • Board Certification: American Board of Otolaryngology, Otolaryngology (2008)
  • Fellowship: Vanderbilt University Dept of Otolaryngology (2008) TN
  • Residency: UCSF Dept of Otolaryngology Head and Neck Surgery (2007) CA
  • Internship: UCSF Dept of General Surgery (2003) CA
  • Medical Education: Harvard Medical School (2002) MA

All Publications


  • Clinical Characteristics and Effects of Vocal Demands in Occupational Voice Users With and Without Primary Muscle Tension Dysphonia. Journal of voice : official journal of the Voice Foundation McDowell, S., Morrison, R., Mau, T., Shembel, A. C. 2025; 39 (2): 448-456

    Abstract

    The objectives of this study were to (1) compare laryngeal configuration patterns in occupational voice users with and without primary muscle tension dysphonia (pMTD), (2) characterize laryngeal configurations in relation to other clinical metrics (acoustic, perceptual), and (3) determine the effects of vocal demands (load) on these clinical parameters.Thirty subjects (15 pMTD, 15 control) were recruited for the study. Laryngoscopic examinations and voice samples for sustained /i/ were obtained before and after a half hour vocal load task. Subjects rated their vocal effort and discomfort before and after the vocal load. Laryngeal configurations were analyzed subjectively with dichotomous and categorical rating scales and hyper function severity quantified (endolaryngeal area outlets). Overall dysphonia severity and vocal instability of each voice sample was rated on 100mm visual analog scales and cepstral peak prominence (CPP) extracted from each voice sample.Laryngeal configurations between groups or vocal load condition were not distinguishable with any of the dichotomous, categorical, or quantitative laryngeal metrics. Vocal effort and discomfort ratings were significantly higher in the pMTD group compared to the control group. Vocal load also had significant effects across groups on vocal effort and vocal tract discomfort ratings. Although CPP values fell within the normal range in both groups, CPP was significantly lower in the pMTD group at both pre-load and post-load time points. Auditory-perceptual ratings were also significantly worse in the pMTD group. Vocal load did not have a significant effect on acoustic or auditory-perceptual measures.Similar laryngeal configurations between groups at both pre- and post-vocal load suggests classic patterns of laryngeal "hyperadduction" may occur variably in occupational voice users and may not be indicative of pMTD pathophysiology. Greater vocal effort, discomfort, instability, and perturbation within the vocal system may better define pMTD than laryngeal configuration in occupational voice users with pMTD.

    View details for DOI 10.1016/j.jvoice.2022.10.005

    View details for PubMedID 36334967

    View details for PubMedCentralID PMC10151438

  • Stereotactic Ablative Radiotherapy for T1 to T2 Glottic Larynx Cancer: Mature Results From the Phase 2 GLoTtic Larynx-SABR Trial. International journal of radiation oncology, biology, physics Sher, D. J., Avkshtol, V., Moon, D., Vo, D., Mau, T., Childs, L., Lin, M. H., Dubas, J., Ahn, C., Sumer, B. D. 2025; 121 (1): 137-144

    Abstract

    Traditional radiation therapy for early-stage larynx cancer irradiates the whole larynx over 5.5 to 6 weeks. Phase 1 data suggest that stereotactic ablative radiotherapy (SABR) is a viable strategy to reduce the irradiated volume and compress treatment time. This phase 2 study evaluated the efficacy of gLoTtic larynx-SABR in 5 or 16 fractions.Eligibility required stage 0 to II squamous cell carcinoma of the glottic larynx. The arytenoid cartilage could not be involved beyond the vocal process, and patients smoking more than one pack per day were excluded. The treatment volume consisted of the gross tumor volume, with a 3 mm margin (5 mm craniocaudal) to create the planning target volume. Patients without active smoking and planning target volume <10 cc received 4250 cGy in 5 fractions, twice per week; other patients received 58.08 Gy in 16 daily fractions. The primary endpoint was the 2-year incidence of local failure.Twenty-five patients were accrued to this study, with 21 and 4 treated with 5 and 16 fractions, respectively. The stage distribution was in situ (n = 1, 4%), T1a/b (n = 16/5, 64%/20%), and T2 (n = 3, 12%). The median age was 72 years, with a prior smoking history in 16 (64%) and active smoking in 1 (4%). At a median follow-up for surviving patients of 3.7 years (IQR, 3.1-4.4 years), there have been 2 in-field recurrences (1 in each dose cohort). The cumulative incidences of local failure were 4% (90% CI, 0.8%-20%) and 8% (90% CI, 3%-24%) at 1 and 2 years, respectively. There have been no acute or late grade 3+ toxicities in disease-free patients. The median baseline, 1, 6, 12, and 24 months Voice Handicap Index scores were 57 (IQR, 32-69), 28.5 (8-48), 4 (0-12), 7.5 (0-12), and 5 (0-24), respectively.Highly conformal stereotactic radiation therapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes. These results need to be interpreted with caution given the small sample size and large noninferiority margin. Additional follow-up and ultimately comparative studies are necessary to validate this paradigm.

    View details for DOI 10.1016/j.ijrobp.2024.07.2147

    View details for PubMedID 39038521

    View details for PubMedCentralID PMC12147862

  • Voice Therapy Expectations for Injured Singers. Journal of voice : official journal of the Voice Foundation Childs, L. F., D'Oto, A., Harris, A., Rao, A., Mau, T. 2024; 38 (6): 1465-1470

    Abstract

    Voice therapy is a mainstay treatment modality in the management of phonotrauma in singers. However, the typical duration of therapy an injured singer undergoes is unknown. The primary aims of the study were to determine (1) the number of therapy sessions preceding a decision for surgery and (2) the number of sessions and length of time to achieve improvement in singers who did not undergo surgery. Whether specific singer factors were associated with the length of therapy was also investigated.Retrospective.Records of singers with phonotraumatic vocal fold lesions seen over a 9-year period at a tertiary care voice center were reviewed.Sixty singers who underwent surgery and 183 singers who did not undergo surgery were included in the final analysis. In nearly ¾ of the surgical patients, five or fewer voice therapy sessions were completed prior to the decision for surgery. Singers who did not undergo surgery required on average 3-4 sessions before noting improvement. Over 60% of the non-surgical singers improved within 3 months and 84% were judged to be improved by 6 months. Lesion type, professional/amateur status, formal voice training, and having a current voice teacher/coach were not associated with the length of voice therapy.The length of voice therapy prior to decision for surgery was limited, and so was the length of therapy leading to initial improvement in singers who did not require surgery. These findings provide a framework for voice therapy expectations and could be reassuring for this unique population.

    View details for DOI 10.1016/j.jvoice.2022.04.014

    View details for PubMedID 35688766

  • Laryngeal and Global Somatosensation in Primary Muscle Tension Dysphonia. Journal of voice : official journal of the Voice Foundation Shembel, A. C., Mau, T., Zafereo, J., Morrison, R., Crocker, C., Moore, A., Khan, A. 2024

    Abstract

    Primary muscle tension dysphonia (pMTD) is a functional voice disorder that reduces communicative abilities and adversely impacts occupational productivity and quality of life. Patients with pMTD report increased vocal effort, fatigue, discomfort, and odynophonia. Although laryngeal and paralaryngeal muscle tension and hyperfunction are the most commonly proposed mechanisms underlying these symptoms, recent studies suggest pMTD may have more to do with the somatosensory system. However, relationships between voice symptoms and somatosensory mechanisms are poorly understood, creating challenges for mechanistic-based pMTD management. The first objective was to compare laryngeal, paralaryngeal, and global somatosensation between subjects with and without pMTD. The second was to determine relationships between pMTD symptoms and somatosensation.Fifty-two (20 pMTD and 32 control) subjects underwent laryngeal sensory testing with aesthesiometers, as well as peripheral mechanosensory and dynamic temporal summation testing to paralaryngeal and limb regions. Voice symptom severities (vocal effort, fatigue, discomfort, and odynophonia) were collected on 100-mm visual analog scales before and after laryngeal sensory testing. Participants also completed the Central Sensitization Inventory.Patients with pMTD reported significantly higher laryngeal sensations (P = 0.0072) and voice symptom severities (P < 0.001) compared with the control group, and had significantly more vocal tract discomfort postlaryngeal sensory testing compared with the prelaryngeal sensory testing timepoint (P = 0.0023). However, there were no significant group differences in laryngeal airway protection responses suggestive of peripheral laryngeal hypersensitivities (P = 0.444). There were also no significant group differences on paralaryngeal or global sensitivities (P > 0.05), and no correlations between severity of voice symptoms and perceptual laryngeal sensations or hypersensitivities (P > 0.05).Patients with pMTD perceive more sensitivities in the larynx and feel more sensations related to the voice (vocal effort, fatigue, discomfort, and pain). However, in general, patients with pMTD do not have abnormal peripheral laryngeal hypersensitivities, increased global somatosensation, or heightened central sensitivity. The lack of significant correlations between peripheral laryngeal hypersensitivities and voice symptom severity ratings suggests these outcome variables target distinct mechanistic constructs.

    View details for DOI 10.1016/j.jvoice.2024.08.003

    View details for PubMedID 39217085

  • Optical Flow Analysis of Paralaryngeal Muscle Movement. The Laryngoscope Morrison, R. A., Fetzer, D. T., Patterson-Lachowicz, A., McDowell, S., Smeltzer, J. C., Mau, T., Shembel, A. C. 2024; 134 (4): 1792-1801

    Abstract

    The paralaryngeal muscles are thought to be hyperfunctional with phonation in patients with primary muscle tension dysphonia (pMTD). However, objective, quantitative tools to assess paralaryngeal movement patterns lack. The objectives of this study were to (1) validate the use of optical flow to characterize paralaryngeal movement patterns with phonation, (2) characterize phonatory optical flow velocities and variability of the paralaryngeal muscles before and after a vocal load challenge, and (3) compare phonatory optical flow measures to standard laryngoscopic, acoustic, and self-perceptual assessments.Phonatory movement velocities and variability of the paralaryngeal muscles at vocal onsets and offsets were quantified from ultrasound videos and optical flow methods across 42 subjects with and without a diagnosis of pMTD, before and after a vocal load challenge. Severity of laryngoscopic mediolateral supraglottic compression, acoustic perturbation, and ratings of vocal effort and discomfort were also obtained at both time points.There were no significant differences in optical flow measures of the paralaryngeal muscles with phonation between patients with pMTD and controls. Patients with pMTD had significantly more supraglottic compression, higher acoustic perturbations, and higher vocal effort and vocal tract discomfort ratings. Vocal load had a significant effect on vocal effort and discomfort but not on supraglottic compression, acoustics, or optical flow measures of the paralaryngeal muscles.Optical flow methods can be used to study paralaryngeal muscle movement velocity and variability patterns during vocal productions, although the role of the paralaryngeal in pMTD diagnostics (e.g., vocal hyperfunction) remains suspect.2 Laryngoscope, 134:1792-1801, 2024.

    View details for DOI 10.1002/lary.31063

    View details for PubMedID 37772838

    View details for PubMedCentralID PMC10947946

  • Management of Bilateral Vocal Fold Paralysis: A Systematic Review. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Lechien, J. R., Hans, S., Mau, T. 2024; 170 (3): 724-735

    Abstract

    To review the current literature about epidemiology, etiologies and surgical management of bilateral vocal fold paralysis (BVFP).PubMED, Scopus, and Cochrane Library.A systematic review of the literature on epidemiology, etiologies, and management of adult patients with BVFP was conducted through preferred reporting items for systematic reviews and meta-analyses statements by 2 investigators.Of the 360 identified papers, 245 were screened, and of these 55 were considered for review. The majority (76.6%) of BVFP cases are iatrogenic. BVFP requires immediate tracheotomy in 36.2% of cases. Laterofixation of the vocal fold was described in 9 studies and is a cost-effective alternative procedure to tracheotomy while awaiting potential recovery. Unilateral and bilateral posterior transverse cordotomy outcomes were reported in 9 and 7 studies, respectively. Both approaches are associated with a 95.1% decannulation rate, adequate airway volume, but voice quality worsening. Unilateral/bilateral partial arytenoidectomy data were described in 4 studies, which reported lower decannulation rate (83%) and better voice quality outcome than cordotomy. Revision rates and complications vary across studies, with complications mainly involving edema, granuloma, fibrosis, and scarring. Selective posterior cricoarytenoid reinnervation is being performed by more surgeons and should be a promising addition to the BVFP surgical armamentarium.Depending on techniques, the management of BVFP may be associated with several degrees of airway improvements while worsened or unchanged voice quality. The heterogeneity between studies, the lack of large-cohort controlled randomized studies and the confusion with posterior glottic stenosis limit the draw of clear conclusion about the superiority of some techniques over others.

    View details for DOI 10.1002/ohn.616

    View details for PubMedID 38123531

  • Extrinsic Laryngeal Muscle Tension in Primary Muscle Tension Dysphonia with Shear Wave Elastography. The Laryngoscope Shembel, A. C., Morrison, R. A., Fetzer, D. T., Patterson-Lachowicz, A., McDowell, S., Comstock Smeltzer, J. C., Mau, T. 2023; 133 (12): 3482-3491

    Abstract

    It has been assumed that patients with primary muscle tension dysphonia (pMTD) have more extrinsic laryngeal muscle (ELM) tension, but tools to study this phenomenon lack. Shear wave elastography (SWE) is a potential method to address these shortcomings. The objectives of this study were to apply SWE to the ELMs, compare SWE measures to standard clinical metrics, and determine group differences in pMTD and typical voice users before and after vocal load.SWE measurements of the ELMs from ultrasound examinations of the anterior neck, supraglottic compression severities from laryngoscopic images, cepstral peak prominences (CPP) from voice recordings, and self-perceptual ratings of vocal effort and discomfort were obtained in voice users with (N = 30) and without (N = 35) pMTD, before and after a vocal load challenge.ELM tension significantly increased from rest-to-voiced conditions in both groups. However, the groups were similar in their ELM stiffness levels at SWE at baseline, during vocalization, and post-vocal load. Levels of vocal effort and discomfort and supraglottic compression were significantly higher and CPP was significantly lower in the pMTD group. Vocal load had a significant effect on vocal effort and discomfort but not on laryngeal or acoustic patterns.SWE can be used to quantify ELM tension with voicing. Although the pMTD group reported significantly higher levels of vocal effort and vocal tract discomfort and, on average, exhibited significantly more severe supraglottic compression and lower CPP values, there were no group differences in levels of ELM tension using SWE.2 Laryngoscope, 133:3482-3491, 2023.

    View details for DOI 10.1002/lary.30830

    View details for PubMedID 37334857

    View details for PubMedCentralID PMC10728340

  • Quantification of False Vocal Fold Hyperfunction During Quiet Breathing in Muscle Tension Dysphonia. The Laryngoscope Han, J., Morrison, R., Mau, T., Shembel, A. C. 2023; 133 (12): 3449-3454

    Abstract

    False vocal fold (FVF) hyperfunction during phonation is thought to be a diagnostic sign of primary muscle tension dysphonia (pMTD). However, hyperfunctional patterns with phonation are also observed in typical speakers. This study tested the hypothesis that FVF posturing during quiet breathing, as measured by the curvature of FVF, could differentiate patients with pMTD from typical speakers.Laryngoscopic images were collected prospectively in 30 subjects with pMTD and 33 typical speakers. Images were acquired at the end of expiration and maximal inspiration during quiet breathing, during sustained /i/, and during loud phonation before and after a 30-min vocal loading task. The FVF curvature (degree of concavity/convexity) was quantified using a novel curvature index (CI, >0 for hyperfunctional/convex, <0 for "relaxed"/concave) and compared between the two groups.At end-expiration, the pMTD group adopted a convex FVF contour, whereas the control group adopted a concave FVF contour (mean CI 0.123 [SEM 0.046] vs. -0.093 [SEM 0.030], p = 0.0002) before vocal loading. At maximal inspiration, the pMTD group had a neutral/straight FVF contour, whereas the control group had a concave FVF contour (mean CI 0.012 [SEM 0.038] vs. -0.155 [SEM 0.018], p = 0.0002). There were no statistically significant differences in FVF curvature between groups in either the sustained voiced or loud conditions. Vocal loading did not change any of these relationships.A hyperfunctional posture of the FVFs during quiet breathing especially at end-expiration may be more indicative of a hyperfunctional voice disorder than supraglottic constriction during voicing.3 Laryngoscope, 133:3449-3454, 2023.

    View details for DOI 10.1002/lary.30814

    View details for PubMedID 37314219

    View details for PubMedCentralID PMC10719413

  • Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis. The Laryngoscope Mau, T., Amin, M. R., Belafsky, P. C., Best, S. R., Friedman, A. D., Klein, A. M., Lott, D. G., Paniello, R. C., Pransky, S. M., Saba, N. F., Howard, T., Dallas, M., Patel, A., Morrow, M. P., Skolnik, J. M. 2023; 133 (11): 3087-3093

    Abstract

    To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433).Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses.An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential.The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP.3 Laryngoscope, 133:3087-3093, 2023.

    View details for DOI 10.1002/lary.30749

    View details for PubMedID 37204106

  • Characteristics of Idiopathic Subglottic Stenosis in the Elderly. The Laryngoscope D'Oto, A., Baker, H., Mau, T., Childs, L. F., Tibbetts, K. M. 2023; 133 (11): 3075-3079

    Abstract

    To compare characteristics of patients ≥65 years presenting with idiopathic subglottic stenosis (iSGS) to patients diagnosed at <65 years. We hypothesize that the groups have similar comorbidities and disease courses.Medical records of patients treated for iSGS at a tertiary care institution from January 2005-September 2022.Patient demographics, time from symptom onset to diagnosis, medical history and comorbidities, and treatment modalities/intervals were recorded and analyzed. Characteristics of patients ≥65 and <65 years at presentation were compared using Chi-square analysis for non-numeric values and the Mann-Whitney U-test for numeric values.One hundred seven patients with iSGS were identified and 16 (15%) were aged ≥65 years (mean age 72.6, 15 female) at presentation. These patients were compared to 91 patients aged <65 years (mean age = 47.6, 90 female). Patients ≥65 years had higher rates of type 2 diabetes mellitus (T2DM) (p = 0.004) and tobacco use (p = 0.004). There were no significant differences in body mass index, gastroesophageal reflux disease, hormone replacement therapy, time from symptom onset to presentation, or length of operative treatment intervals.Patients ≥65 years with iSGS have higher rates of tobacco use, suggesting that alterations in wound healing may play a role in the development of iSGS in this age group. Although rates of T2DM were higher in the elderly group, clinical significance may be limited given the overall higher rate of diabetes mellitus in the elderly population.4 Laryngoscope, 133:3075-3079, 2023.

    View details for DOI 10.1002/lary.30742

    View details for PubMedID 37166144

  • Ultrafast Laser Microlaryngeal Surgery for In Vivo Subepithelial Void Creation in Canine Vocal Folds. The Laryngoscope Andrus, L., Camli, B., Mau, T., Ben-Yakar, A. 2023; 133 (11): 3042-3048

    Abstract

    Tightly-focused ultrafast laser pulses (pulse widths of 100 fs-10 ps) provide high peak intensities to produce a spatially confined tissue ablation effect. The creation of sub-epithelial voids within scarred vocal folds (VFs) via ultrafast laser ablation may help to localize injectable biomaterials to treat VF scarring. Here, we demonstrate the feasibility of this technique in an animal model using a custom-designed endolaryngeal laser surgery probe.Unilateral VF mucosal injuries were created in two canines. Four months later, ultrashort laser pulses (5 ps pulses at 500 kHz) were delivered via the custom laser probe to create sub-epithelial voids of ~3 × 3-mm2 in both healthy and scarred VFs. PEG-rhodamine was injected into these voids. Ex vivo optical imaging and histology were used to assess void morphology and biomaterial localization.Large sub-epithelial voids were observed in both healthy and scarred VFs immediately following in vivo laser treatment. Two-photon imaging and histology confirmed ~3-mm wide subsurface voids in healthy and scarred VFs of canine #2. Biomaterial localization within a void created in the scarred VF of canine #2 was confirmed with fluorescence imaging but was not visualized during follow-up two-photon imaging. As an alternative, the biomaterial was injected into the excised VF and could be observed to localize within the void.We demonstrated sub-epithelial void formation and the ability to inject biomaterials into voids in a chronic VF scarring model. This proof-of-concept study provides preliminary evidence towards the clinical feasibility of such an approach to treating VF scarring using injectable biomaterials.N/A Laryngoscope, 133:3042-3048, 2023.

    View details for DOI 10.1002/lary.30713

    View details for PubMedID 37096749

    View details for PubMedCentralID PMC10754041

  • Relationships Between Laryngoscopic Analysis Metrics of Supraglottic Compression and Vocal Effort in Primary Muscle Tension Dysphonia. Journal of voice : official journal of the Voice Foundation Shembel, A. C., Morrison, R. A., McDowell, S., Smeltzer, J. C., Crocker, C., Bell, C., Mau, T. 2023

    Abstract

    Supraglottic compression is thought to underlie vocal effort in patients with primary muscle tension dysphonia (pMTD). However, the relationship between supraglottic compression and vocal effort in this clinical population remains unclear. Gold standard laryngoscopic assessment metrics for supraglottic compression are also lacking. The goals of this study were to identify metrics proposed in the literature that could distinguish patients diagnosed with pMTD from typical voice users and determine their relationships to the vocal effort.Flexible laryngeal endoscopy was performed on 50 participants (25 pMTD, 25 controls). The presence of supraglottic compression was characterized using a categorical (nominal) scale and severity was quantified on ordinal and continuous scales. The three laryngoscopic metrics were correlated with self-perceived ratings of vocal effort on a 100 mm visual analog scale.Inter-rater reliability was strongest for the continuous scale (P's < 0.0001) compared to categorical (P's < 0.001) and ordinal (P's < 0.001) scales. The presence of different supraglottic compression patterns varied in both groups, and there were no significant group differences on categorical (P's > 0.05) scales. Mediolateral (M-L) supraglottic compression was significantly greater in the pMTD group (P < 0.0001), and anteroposterior (A-P) compression was significantly greater in the control group (P = 0.001) using continuous scales. There were no significant relationships between any of the three laryngoscopic metric types and vocal effort ratings (P's > 0.05), except for a significantly positive relationship between anterior-posterior compression on the ordinal scale and vocal effort in the control group (P = 0.047).Continuous scales are reliable and valid for distinguishing individuals with pMTD from those without voice disorders, especially occupational voice users. M-L supraglottic compression may be a better indicator of pMTD than A-P compression. However, the poor correlation between supraglottic compression and vocal effort suggests that one may not influence the other. Future studies should focus on other mechanisms underlying vocal effort in patients with pMTD.

    View details for DOI 10.1016/j.jvoice.2023.06.011

    View details for PubMedID 37865541

  • Association of Genre of Singing and Phonotraumatic Vocal Fold Lesions in Singers. The Laryngoscope Childs, L. F., D'Oto, A., Beams, D. R., Hynan, L., Mau, T. 2023; 133 (7): 1683-1689

    Abstract

    To determine if (1) the likelihood of presenting with phonotraumatic lesions differs by singing genre in treatment-seeking singers and (2) if the distribution of phonotraumatic lesion types differs by singing genre.Retrospective.Records of singers who presented with a voice complaint over the course of 2.5 years (June 2017-December 2019) were reviewed to determine the proportion of those with phonotraumatic lesions as a function of genre (Study 1). Separately, the lesion types and genres of singers diagnosed with phonotraumatic lesions over a 9-year period (July 2011-March 2020) were determined (Study 2).In Study 1, 191 of 712 (26.8%) dysphonic singers were diagnosed with phonotraumatic lesions. Country/folk, gospel/jazz, and musical theater singers were more likely to present with phonotraumatic lesions. In Study 2, in 443 singers with phonotraumatic lesions, polyps and pseudocysts, but not nodules, were found to be distributed unequally across genres (χ2 p = 0.006, p < 0.0001, p = 0.064, respectively). Praise/worship singers had significantly higher proportions of polyps compared to choral singers (OR 4.8 [95% CI 1.9-12.5]) or compared to musical theater singers (OR 7.2 [95% CI 2.5-20.8]). Opera singers had significantly higher proportions of pseudocysts than choral singers (OR 3.1 [95% CI 1.5-6.1]) or musical theater singers (OR 3.7 [95% CI 1.8-7.6]).The higher incidence of polyps in praise/worship singers likely reflects the more emphatic nature of singing and the tendency for acute injury. The higher incidence of pseudocysts in opera singers may reflect a more chronic nature of injury.4 Laryngoscope, 133:1683-1689, 2023.

    View details for DOI 10.1002/lary.30414

    View details for PubMedID 36196907

  • Ingredients in the Visual Perception of Hypomobile Vocal Fold Motion Impairment. The Laryngoscope Han, J., George, S. S., Mau, T. 2023; 133 (4): 866-874

    Abstract

    The clinical determination of vocal fold (VF) hypomobility based on laryngoscopy is subjective. Previous studies point to VF motion anomaly as the most commonly reported factor in the diagnosis of hypomobility. This study tested the hypotheses that VF angular velocities and angular range of motion (ROM) differ between the two VFs in cases of unilateral VF hypomobility.Retrospective.Semi-automated analysis of laryngoscopic videos of 18 subjects diagnosed with unilateral VF hypomobility and 13 subjects with normal VF mobility was performed to quantify/compare the VF angular velocity and ROM between the two VFs during /i/-sniff and laugh.In the hypomobile VF group, 7 out of 15 (47%) videos with /i/-sniff and 5 out of 8 (63%) with laugh had a statistically significant difference in the angular velocities between the VFs in either abduction or adduction. For VF ROM, 8 out of 15 (53%) /i/-sniff videos and 4 out of 8 (50%) with laughter had a statistically significant difference between VFs. In the group without the diagnosis of VF hypomobility, 9 out of 13 subjects (69%) had no difference in VF angular velocity and ROM during either /i/-sniff or laugh.Differences in VF angular velocity or ROM are measurable in a substantial subset of subjects diagnosed with unilateral VF hypomobility. Clinicians' ability to gauge VF motion goes beyond what can be extracted from frame-by-frame analysis. Other visual cues, in addition to VF angular velocity and ROM, likely contribute to the perception of unilateral VF hypomobility.3 Laryngoscope, 133:866-874, 2023.

    View details for DOI 10.1002/lary.30290

    View details for PubMedID 35822396

  • Ultrafast laser surgery probe for sub-surface ablation to enable biomaterial injection in vocal folds. Scientific reports Andrus, L., Jeon, H., Pawlowski, M., Debord, B., Gerome, F., Benabid, F., Mau, T., Tkaczyk, T., Ben-Yakar, A. 2022; 12 (1): 20554

    Abstract

    Creation of sub-epithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable therapeutic biomaterials towards an improved treatment for vocal fold scarring. Several ultrafast laser surgery probes have been developed for precise ablation of surface tissues; however, these probes lack the tight beam focusing required for sub-surface ablation in highly scattering tissues such as vocal folds. Here, we present a miniaturized ultrafast laser surgery probe designed to perform sub-epithelial ablation in vocal folds. The requirement of high numerical aperture for sub-surface ablation, in addition to the small form factor and side-firing architecture required for clinical use, made for a challenging optical design. An Inhibited Coupling guiding Kagome hollow core photonic crystal fiber delivered micro-Joule level ultrashort pulses from a high repetition rate fiber laser towards a custom-built miniaturized objective, producing a 1/e2 focal beam radius of 1.12 ± 0.10 μm and covering a 46 × 46 μm2 scan area. The probe could deliver up to 3.8 μJ pulses to the tissue surface at 40% transmission efficiency through the entire system, providing significantly higher fluences at the focal plane than were required for sub-epithelial ablation. To assess surgical performance, we performed ablation studies on freshly excised porcine hemi-larynges and found that large area sub-epithelial voids could be created within vocal folds by mechanically translating the probe tip across the tissue surface using external stages. Finally, injection of a model biomaterial into a 1 × 2 mm2 void created 114 ± 30 μm beneath the vocal fold epithelium surface indicated improved localization when compared to direct injection into the tissue without a void, suggesting that our probe may be useful for pre-clinical evaluation of injectable therapeutic biomaterials for vocal fold scarring therapy. With future developments, the surgical system presented here may enable treatment of vocal fold scarring in a clinical setting.

    View details for DOI 10.1038/s41598-022-24446-5

    View details for PubMedID 36446830

    View details for PubMedCentralID PMC9708667

  • Profile of Injured Singers: Expectations and Insights. The Laryngoscope Childs, L. F., Rao, A., Mau, T. 2022; 132 (11): 2180-2186

    Abstract

    To discover patterns of phonotraumatic lesions in singers and investigate factors that differentiate those who underwent surgery from those who did not. We hypothesized that 1) lesion type distribution differs by age, sex, singer classification (professional/amateur), and history of formal voice training; 2) the likelihood of surgery is associated with singer classification and voice training.Retrospective.Retrospective review of 438 singers with phonotraumatic lesions over a 9-year period. Lesion type distribution was analyzed with respect to sex, age, singer classification, and voice training. The association of eventual surgery with these factors was also analyzed.Nodules accounted for over half of the cohort (58%), followed by pseudocysts (20%), polyps (14%), and cysts (4%). Nearly two of every three injured female singers, but fewer than one out of every three injured male singers, had nodules. In contrast, over half of the injured males had polyps, whereas only 6% of injured females had polyps. In females, polyps occurred at a later age, and in males, nodules occurred at a younger age compared to other lesion types. Only 14% of the total cohort eventually underwent surgery. Professional singers without formal voice training were almost eight times more likely to have undergone surgery than amateur singers with voice training.Professional singers were more likely to undergo surgery than amateurs, and formal voice training was associated with a lower likelihood of surgery. The observation that polyps tended to occur in older women may have implications for the pathogenesis of vocal fold polyps.4 Laryngoscope, 132:2180-2186, 2022.

    View details for DOI 10.1002/lary.30015

    View details for PubMedID 35023577

  • Multicenter Development and Validation of the Vocal Cord Paralysis Experience (CoPE), a Patient-Reported Outcome Measure for Unilateral Vocal Fold Paralysis-Specific Disability. JAMA otolaryngology-- head & neck surgery Fernandes-Taylor, S., Damico-Smith, C., Arroyo, N., Wichmann, M., Zhao, J., Feurer, I. D., Francis, D. O. 2022; 148 (8): 756-763

    Abstract

    Unilateral vocal fold paralysis (UVFP) is a common and life-changing complication of cancer, trauma, and an estimated 500 000 head, neck, and chest surgeries performed annually in the US, among other causes (eg, idiopathic). Consequent disabilities are profound and often permanent and can include severe voice, swallowing, and breathing dysfunction and concomitant anxiety, isolation, and fear. Physiological measures often correlate poorly with patient-reported disability. The measure described herein was designed to be a comprehensive, psychometrically sound UVFP-specific patient-reported outcome measure (PROM) for use in clinical trials or at point of care.To evaluate the reliability and validity of the CoPE (vocal Cord Paralysis Experience) PROM in a nationally representative sample for both clinical and research use.This survey validation study was performed at 34 tertiary care centers across the US and included English-speaking adults with unilateral vocal fold immobility confirmed via laryngoscopy.Reliability (internal consistency, alternate form, and test-retest) and validity (convergent and known-group).In total, 613 patients (mean [SD] age, 58 [15.3] years; 394 [64.5%] women) were recruited, and 555 (92.3%) completed surveys for all time points. Internal consistency was high in the overall 22-item PROM and psychosocial, swallow, and voice subscales (Cronbach α > 0.91). Intraclass correlations for individuals between the baseline and 2-week administrations were moderate for the overall score and subscales (intraclass correlations range, 0.66-0.80). There were significant differences between the online and 2-week paper administrations for the overall score and voice and psychosocial subscales (overall scale mean: 54.4 [95% CI, 49.7-59.1] vs 48.9 [95% CI, 43.7-54.0] at 2 weeks). The confirmatory model was found to be suitably fitted based on average r2 values 0.5 or greater for subscale and overall scores. Correlations between subscales and existing PROMs (Voice-Related Quality of Life, Eating Assessment Tool, and Communication Participation Item Bank) were all greater than 0.69, and mean PROM subscale scores were significantly different across known quartiles of existing PROMs.The findings of this survey validation study suggest that the CoPE PROM could serve as a psychometrically sound, comprehensive measure of UVFP-attributed disability suitable for use in clinical and research settings to assess within-person changes. The results will inform a user manual to facilitate use in clinical trials comparing the effectiveness and durability of treatments including behavioral (speech therapy), temporary (eg, injection augmentation), and permanent surgical treatments for UVFP.

    View details for DOI 10.1001/jamaoto.2022.1545

    View details for PubMedID 35797026

    View details for PubMedCentralID PMC9264235

  • Combining Voice Rest and Steroids to Improve Diagnostic Clarity in Phonotraumatic Vocal Fold Injury. Journal of voice : official journal of the Voice Foundation Childs, L. F., Mau, T. 2022; 36 (3): 403-409

    Abstract

    (1) To describe a combination voice rest and steroid regimen to clarify ambiguous diagnoses in singers who present with phonotraumatic lesions and (2) to determine which videostroboscopic parameters show the most consistent response to this regimen.Chart review.Singers with phonotraumatic vocal fold lesions seen at a tertiary care voice center over a 10-year period were identified. Those who had uncertain diagnoses on initial presentation, completed a combination regimen including voice rest and steroids, and had follow-up examinations were included in the analysis. The effect of this combination regimen was assessed by ratings of pre- and postregimen videostroboscopy examinations and by auditory perceptual ratings. Whether the combination regimen clarified the diagnosis was noted.Twenty-nine singers were prescribed the combination regimen with the intent to clarify the diagnosis. In 79% (23/29) of these singers, the regimen helped clarify diagnosis, for example, ruling in or ruling out specific lesions, confirming areas of scar, or distinguishing acute from chronic phonotraumatic injury. Stroboscopic exams were improved in 86% (25/29). The most common stroboscopic finding was a reduction in the lesion size (66%). Auditory perceptual ratings improved in 48% (14/29) of patients.A "cool down" combination of voice rest and steroids can improve diagnostic clarity in a subset of singers with phonotraumatic lesions. This combination regimen can be considered, with both the side effect profile of steroids and possible financial ramifications of strict voice rest in mind, when the initial diagnosis is unclear.

    View details for DOI 10.1016/j.jvoice.2020.06.003

    View details for PubMedID 32654865

  • Data Augmentation for End-to-end Silent Speech Recognition for Laryngectomees Cao, B., Teplansky, K., Sebkhi, N., Bhaysar, A., Inan, O. T., Samlan, R., Mau, T., Wang, J., Int Speech Commun Assoc ISCA-INT SPEECH COMMUNICATION ASSOC. 2022: 3653-3657
  • Surgical Anatomy of the Nose: A Foundation for Rhinoplasty Bailey’s Head and Neck Surgery-Otolaryngology Polacco, M. A., Kim, D. W., Mau, T. 2022
  • Patterns of Recurrence of Phonotraumatic Vocal Fold Lesions Suggest Distinct Mechanisms of Injury. The Laryngoscope Lee, M., Mau, T., Sulica, L. 2021; 131 (11): 2523-2529

    Abstract

    To examine patterns of recurrence of benign phonotraumatic vocal fold lesions over time for insights into pathophysiology.Case series with mathematical modeling.Medical records and stroboscopic exams of adults who underwent microlaryngoscopic resection of phonotraumatic vocal fold lesions over a 13-year period were reviewed for time to recurrence after surgery. Uniform and log-normal probability distributions were fitted to the time to recurrence curves for vocal fold polyps, midfold masses, and pseudocysts. Model fits were compared using the Akaike information criterion corrected, a standard measure of the goodness of fit. Stochastic simulations were used to verify that the mechanistic hypotheses were concordant with the selected probability distributions and empiric data.Of 567 patients who underwent microlaryngoscopic resection, 65 had a recurrence (16 polyps, 14 midfold masses, and 35 pseudocysts). Midfold mass and pseudocyst recurrences were predominantly seen in younger women. Polyps were best fit by a uniform distribution rather than log-normal, whereas midfold masses and pseudocysts were better fit by log-normal rather than uniform. Stochastic simulations suggest that polyps recur sporadically according to a paroxysmal-developmental model, whereas midfold mass and pseudocyst recurrences follow a force-multiplication, damage-accumulation process.Vocal fold polyps are acute lesions evenly distributed by age and gender that recur uniformly over time, suggesting they arise from sudden tissue reactions to phonotraumatic stress. Pseudocysts and midfold fibrous masses are chronic lesions predominantly found in young women that recur with log-normal distribution over time, suggesting gradual damage accumulation in larynges predisposed to enhanced phonotrauma.4 Laryngoscope, 131:2523-2529, 2021.

    View details for DOI 10.1002/lary.29531

    View details for PubMedID 33835504

  • Understanding Risk and Recovery in Vocal Fold Paralysis CURRENT OTORHINOLARYNGOLOGY REPORTS Mau, T. 2021; 9 (2): 95-100
  • Impact of Patient Factors and Management Strategies on Outcomes After Transverse Posterior Cordotomy. The Laryngoscope Qazi, S., Mau, T., Tibbetts, K. M. 2021; 131 (5): 1066-1070

    Abstract

    Carbon dioxide laser transverse posterior cordotomy (TPC) aims to improve airway aperture in patients with glottic obstruction. Postoperative complications may worsen airway compromise and necessitate additional interventions. We sought to identify factors impacting outcomes after TPC.Retrospective chart review.Medical records of patients who underwent TPC for glottic airway obstruction at a tertiary-care medical center between 2008 and 2018 were reviewed. Demographics, comorbidities, and intra- and postoperative management strategies were analyzed.Twenty patients who underwent TPC for glottic airway obstruction met inclusion criteria. The mean age was 57 years, and 13 patients were female. Mean follow-up time was 442 days. Seven patients had posterior glottic stenosis, and 13 had bilateral vocal fold paralysis. Twelve patients developed postoperative complications including granuloma formation (four patients), hospital readmission for dyspnea due to glottic edema (five patients), need for revision surgery (nine patients), or failure to decannulate tracheotomy (five patients). Eight patients had an uncomplicated recovery with improved dyspnea, with two patients with tracheotomies decannulated. Patients with a history of smoking tobacco were more likely to experience complications (P = .035). There were no significant differences in outcomes with respect to history of head and neck radiation or gastroesophageal reflux disease. Steroid injection at the surgical site and postoperative medications did not significantly impact outcomes. With respect to granuloma formation, none of the variables analyzed reached significance.History of tobacco use increases complication rates after TPC. Other patient comorbidities and intra- and postoperative management strategies do not impact outcomes.4 Laryngoscope, 131:1066-1070, 2021.

    View details for DOI 10.1002/lary.28931

    View details for PubMedID 32678917

  • Vocal Tradeoffs in Anterior Glottoplasty for Voice Feminization. The Laryngoscope Titze, I. R., Palaparthi, A., Mau, T. 2021; 131 (5): 1081-1087

    Abstract

    Anterior (Wendler) glottoplasty has become a popular surgery for voice feminization. However, there has been some discrepancy between its theoretical pitch-raising potential and what is actually achievable, and downsides to shortening the glottis have not been fully explored. In addition, descriptions of the surgery are inconsistent in their treatment of the vocal ligament. This study aimed to determine 1) how fundamental frequency (fo ) is expected to vary with length of anterior glottic fixation, 2) the impact of glottic shortening on sound pressure level (SPL), and 3) the effect of including the ligament in fixation.Computational simulation.Voice production was simulated in a fiber-gel finite element computational model using canonical male vocal fold geometry incorporating a three-layer vocal fold composition (superficial lamina propria, vocal ligament, and thyroarytenoid muscle). Progressive anterior glottic fixation (0, 1/8, 2/8, 3/8, etc. up to 7/8 of membranous vocal fold length) was simulated. Outcome measures were fo , SPL, and glottal flow waveforms.fo increased from 110 Hz to 164 Hz when the anterior one-half vocal fold was fixed and continued to progressively rise with further fixation. SPL progressively decreased beyond 1/8 to 1/4 fixation. Inclusion of the vocal ligament in fixation did not further increase fo . Any fixation increased aperiodicity in the acoustic signal.The optimal length of fixation is a compromise between pitch elevation and reduction in output acoustic power. The simulation also provided a potential explanation for vocal roughness that is sometimes noted after anterior glottoplasty.NA Laryngoscope, 131:1081-1087, 2021.

    View details for DOI 10.1002/lary.28940

    View details for PubMedID 32840877

    View details for PubMedCentralID PMC9285120

  • Intraoperative Airway Management Considerations for Adult Patients Presenting With Tracheostomy: A Narrative Review. Anesthesia and analgesia Rosero, E. B., Corbett, J., Mau, T., Joshi, G. P. 2021; 132 (4): 1003-1011

    Abstract

    Tracheotomy is a surgical procedure through which a tracheostomy, an opening into the trachea, is created. Indications for tracheostomy include facilitation of airway management during prolonged mechanical ventilation, treatment of acute upper airway obstruction when tracheal intubation is unfeasible, management of chronic upper airway obstructive conditions, and planned airway management for major head and neck surgery. Patients who have a recent or long-term tracheostomy may present for a variety of surgical or diagnostic procedures performed under general anesthesia or sedation/analgesia. Airway management of these patients can be challenging and should be planned ahead of time. Anesthesia personnel should be familiar with the different components of cuffed and uncuffed tracheostomy devices and their connectivity to the anesthesia circuits. An appropriate airway management plan should take into account the indication of the tracheostomy, the maturity status of the stoma, the type and size of tracheostomy tube, the expected patient positioning, and presence of patient's concurrent health conditions. Management of the patient with a T-tube is highlighted. Importantly, there is a need for multidisciplinary care involving anesthesiologists, surgical specialists, and perioperative nurses. The aim of this narrative review is to discuss the anesthesia care of patients with a tracheostomy. Key aspects on relevant tracheal anatomy, tracheostomy tubes/devices, alternatives of airway management, and possible complications related to tracheostomy are summarized with a recommendation for an algorithm to manage intraoperative tracheostomy tube dislodgement.

    View details for DOI 10.1213/ANE.0000000000005330

    View details for PubMedID 33369928

  • Considerations in Vocal Fold Injection Patología Laríngea y Fonocirugía Mau, T., Childs, L. F. 2021
  • Investigating Speech Reconstruction for Laryngectomees for Silent Speech Interfaces Cao, B., Sebkhi, N., Bhaysar, A., Irian, O. T., Samlan, R., Mau, T., Wang, J., Int Speech Commun Assoc ISCA-INT SPEECH COMMUNICATION ASSOC. 2021: 651-655
  • Effect of Vocal Fold Implant Placement on Depth of Vibration and Vocal Output. The Laryngoscope Smith, S. L., Titze, I. R., Storck, C., Mau, T. 2020; 130 (9): 2192-2198

    Abstract

    Most type 1 thyroplasty implants and some common injectable materials are mechanically stiff. Placing them close to the supple vocal fold mucosa can potentially dampen vibration and adversely impact phonation, yet this effect has not been systematically investigated. This study aims to examine the effect of implant depth on vocal fold vibration and vocal output.Computational simulation.Voice production was simulated with a fiber-gel finite element computational model that incorporates a three-layer vocal fold composition (superficial lamina propria, vocal ligament, thyroarytenoid muscle). Implants of various depths were simulated, with a "deeper" or more medial implant positioned closer to the vocal fold mucosa and replacing more muscle elements. Trajectories of surface and within-tissue nodal points during vibration were produced. Outcome measures were the trajectory radii, fundamental frequency (F0 ), sound pressure level (SPL), and smoothed cepstral peak prominence (CPPS) as a function of implant depth.Amplitude of vibration at the vocal fold medial surface was reduced by an implant depth of as little as 14% of the total transverse vocal fold depth. Increase in F0 and decrease in CPPS were noted beyond 30% to 40% implant depth, and SPL decreased beyond 40% to 60% implant depth.Commonly used implants can dampen vibration "from a distance," ie, even without being immediately adjacent to vocal fold mucosa. Since implants are typically placed at depths examined in this study, stiff implants likely have a negative vocal impact in a subset of patients. Softer materials may be preferable, especially in bilateral medialization procedures.N/A Laryngoscope, 130:2192-2198, 2020.

    View details for DOI 10.1002/lary.28365

    View details for PubMedID 31643091

    View details for PubMedCentralID PMC7382902

  • Pathophysiology of iatrogenic and idiopathic vocal fold paralysis may be distinct. The Laryngoscope Mau, T., Husain, S., Sulica, L. 2020; 130 (6): 1520-1524

    Abstract

    Spontaneous vocal recovery from idiopathic vocal fold paralysis (VFP) appears to differ in time course from recovery in iatrogenic VFP. This study aimed to determine if this difference could be explained by differing mechanisms causing recurrent laryngeal nerve (RLN) dysfunction, specifically whether idiopathic VFP is consistent with a focal RLN axonal lesion.Case series with mathematical modeling.A review of 1267 cases of unilateral VFP over a 10-year period yielded 114 subjects (35 idiopathic, 79 iatrogenic) with a discrete onset of spontaneous vocal recovery. The time-to-recovery data were fit to a previously described two-phase model that incorporates the Seddon classification of neuropraxia and higher grades of axonal injury. Alternatively, the data were fit to a single phase model that does not assume a focal axonal lesion.Time to vocal recovery in iatrogenic VFP can be reliably modeled by the assumption of a focal axonal lesion, with an early recovery group corresponding to neuropraxia and a late recovery group with more severe nerve damage. Time to recovery in idiopathic VFP can be more simply modeled in a single phase, with a time course that mirrors those in diverse biological processes such as transcription and microtubule growth.Idiopathic VFP may not be caused by a focal axonal lesion. Neuritis may be a compatible mechanism. The iatrogenic VFP data lend further support to the concept that the severity of RLN injury, not the length of axon to regenerate, is the chief determinant of recovery time after iatrogenic injury.4 Laryngoscope, 130:1520-1524, 2020.

    View details for DOI 10.1002/lary.28281

    View details for PubMedID 31498451

  • Primary odynophonia: When pain is out of proportion to dysphonia. The Laryngoscope Kim, S. I., Atkinson, C., Harris, A. H., Tibbetts, K., Mau, T. 2020; 130 (4): E183-E189

    Abstract

    Odynophonia is generally regarded as a symptom of a voice disorder. However, a subset of patients with odynophonia have debilitating pain out of proportion to the relatively mild degree of dysphonia and are not responsive to voice therapy. The goals of this study were to 1) describe the symptomatology of this subset of patients and differentiate it from typical odynophonia, 2) propose alternate models to explain this phenomenon of primary odynophonia, and 3) present a new treatment paradigm based on the proposed models.Case series.Inclusion criteria were complaint of persistent pain associated with voicing, normal vocal fold mobility, complete glottic closure, and limited or lack of response of pain to voice therapy. Presenting symptoms, voice evaluation, and treatment outcomes were reviewed.Eleven patients fit the inclusion criteria. The degree of pain did not follow the trajectory of vocal improvement with therapy. The pain was stagnant or worsened with voice exercises. The most dramatic improvement came about in one patient who received false vocal fold Botox injections, and another who received thyrohyoid lidocaine/triamcinolone injection. We propose that these patients had developed primary odynophonia, in which the pain had become self-sustaining and no longer responded to correction of hyperfunctional vocal behavior. The mechanism of pain persistence may involve superior laryngeal neuralgia, cartilaginous or ligamentous inflammation, and/or central sensitization.A minority of patients have primary odynophonia distinct from typical odynophonia. Direct treatment of pain may be advisable prior to or in conjunction with voice therapy.4 Laryngoscope, 130:E183-E189, 2020.

    View details for DOI 10.1002/lary.28154

    View details for PubMedID 31237699

  • Tongue and Lip Motion Patterns in Alaryngeal Speech Teplansky, K. J., Wisler, A., Cao, B., Liang, W., Whited, C. W., Mau, T., Wang, J., Int Speech Commun Assoc ISCA-INT SPEECH COMMUNICATION ASSOC. 2020: 4576-4580
  • A tissue-specific, injectable acellular gel for the treatment of chronic vocal fold scarring. Acta biomaterialia Xu, C. C., Mau, T. 2019; 99: 141-153

    Abstract

    Gel-based injectable biomaterials have significant potential for treating vocal fold defects such as scarring. An ideal injectable for vocal fold lamina propria restoration should mimic the microenvironment of the lamina propria to induce scarless wound healing and functional tissue regeneration. Most current synthetic or natural injectable biomaterials do not possess the same level of complex, tissue-specific constituents as the natural vocal fold lamina propria. In this study we present a newly-developed injectable gel fabricated from decellularized bovine vocal fold lamina propria. Blyscan assay and mass spectrometry indicated that the vocal fold-specific gel contained a large amount of sulfated glycosaminoglycans and over 250 proteins. Gene Ontology overrepresentation analysis revealed that the proteins in the gel dominantly promote antifibrotic biological process. In vivo study using a rabbit vocal fold injury model showed that the injectable gel significantly reduced collagen density and decreased tissue contraction of the lamina propria in vocal folds with chronic scarring. Furthermore, this acellular gel only elicited minimal humoral immune response after injection. Our findings suggested that the tissue-specific, injectable extracellular matrix gel could be a promising biomaterial for treating vocal fold scarring, even after the formation of mature scar. STATEMENT OF SIGNIFICANCE: Vocal fold lamina propria scarring remains among the foremost therapeutic challenges in the management of patients with voice disorders. Surgical excision of scar may cause secondary scarring and yield inconsistent results. The present study reports an extracellular matrix-derived biomaterial that demonstrated antifibrotic effect on chronic scarring in vocal fold lamina propria. Its injectability minimizes the invasiveness of the delivery procedure and the degree of mucosal violation. In this work we also describe a new methodology which can more accurately identify proteins from the complex mixture of an acellular extracellular matrix gel by excluding interfering peptides produced during the enzymatic digestion in gel fabrication.

    View details for DOI 10.1016/j.actbio.2019.08.025

    View details for PubMedID 31425889

    View details for PubMedCentralID PMC6851489

  • Scattering properties and femtosecond laser ablation thresholds of human and canine vocal folds at 776-nm wavelength. Journal of biomedical optics Andrus, L., Mau, T., Ben-Yakar, A. 2019; 24 (8): 1-7

    Abstract

    Ultrafast laser ablation may provide a treatment for vocal fold (VF) scarring. Optical properties of VFs must be known prior to clinical implementation to select appropriate laser surgery conditions. We present scattering lengths of epithelium ℓs  ,  ep, superficial lamina propria ℓs  ,  SLP, and ablation thresholds Fth of human and canine VF tissues. Our experimental approach involves an image-guided, laser-ablation-based method that allows for simultaneous determination of ℓs and Fth in these multilayered tissues. Studying eight canine samples, we found ℓs  ,  ep  =  75.3  ±  5.7  μm, ℓs  ,  SLP  =  26.1  ±  1.2  μm, Fth  ,  ep  =  1.58  ±  0.06  J  /  cm2, and Fth  ,  SLP  =  1.55  ±  0.17  J  /  cm2. Studying five human samples, we found ℓs  ,  ep  =  42.8  ±  3.3  μm and Fth  ,  ep  =  1.66  ±  0.10  J  /  cm2. We studied the effects of cumulative pulse overlap on ablation threshold and found no significant variations beyond 12 overlapping pulses. Interestingly, our studies about the effect of sample storage on the scattering properties of porcine VF show a 60% increase in ℓs  ,  ep for fresh porcine VF when compared to the same sample stored in isotonic solution. These results provide guidelines for clinical implementation by enabling selection of optimal laser surgery parameters for subsurface ablation of VF tissues.

    View details for DOI 10.1117/1.JBO.24.8.085005

    View details for PubMedID 31468749

    View details for PubMedCentralID PMC6983523

  • Intervention Outcomes of Two Treatments for Muscle Tension Dysphonia: A Randomized Controlled Trial. Journal of speech, language, and hearing research : JSLHR Watts, C. R., Hamilton, A., Toles, L., Childs, L., Mau, T. 2019; 62 (2): 272-282

    Abstract

    Purpose The aim of this study was to test the hypothesis that stretch-and-flow voice therapy (SnF) is noninferior to resonant voice therapy (RVT) for speakers with muscle tension dysphonia. Method Participants with primary muscle tension dysphonia were randomly assigned to 1 of 2 treatment groups. Participants received 6 sessions of either SnF or RVT for 6 weeks (1 session per week). Pretreatment and posttreatment audio recordings of sustained vowels and connected speech were acquired. Response to treatment was assessed using the voice handicap index (VHI) as the primary outcome measure. Secondary outcome measures included the acoustic voice quality index, the smoothed cepstral peak prominence, and scales from the Consensus Auditory-Perceptual Evaluation of Voice instrument. Data were analyzed for 21 participants who completed the study (12 in the SnF group, 9 in the RVT group). Results Direction of change for the primary outcome measure and all 3 secondary outcome measures at posttreatment was in the direction of improvement for both SnF and RVT. Confidence intervals for VHI measures did not cross the null effect line on forest plots, suggesting significant effects for both treatments on the primary outcome measure. The effect sizes for pretreatment to posttreatment changes in VHI were large for both treatment groups. Similar results were found for the secondary acoustic outcome measures. There were statistically significant pretreatment to posttreatment changes in the primary and secondary outcome measures for patients receiving both treatments, indicating significant improvement in response to both RVT and SnF. There were no statistically significant differences in pretreatment to posttreatment changes in the primary outcome measure or any secondary outcome measure between the two groups. The within-group pretreatment to posttreatment changes in Consensus Auditory-Perceptual Evaluation of Voice scales did not reach statistical significance for either RVT or SnF. Conclusions Both SnF and RVT produced positive treatment response in speakers with muscle tension dysphonia, with no statistically significant difference in the outcome measures between the two treatments. This suggests that SnF is noninferior to RVT and that both are effective options for treating vocal hyperfunction. Results from this study also support previous findings documenting the sensitivity of multidimensional acoustic measurements to treatment response.

    View details for DOI 10.1044/2018_JSLHR-S-18-0118

    View details for PubMedID 30950698

  • A computational study of depth of vibration into vocal fold tissues. The Journal of the Acoustical Society of America Palaparthi, A., Smith, S., Mau, T., Titze, I. R. 2019; 145 (2): 881

    Abstract

    The effective depth of vocal fold vibration is self-regulated and generally not known a priori in vocalization. In this study, the effective depth was quantified systematically under various phonatory conditions using a fiber-gel finite element vocal fold model. The horizontal and vertical excursions of each finite element nodal point trajectory were recorded to compute trajectory areas. The extent of vibration was then studied based on the variation of trajectory radii as a function of depth in several coronal sections along the anterior-posterior direction. The results suggested that the vocal fold nodal trajectory excursions decrease systematically as a function of depth but are affected by the layered structure of the vocal folds. The effective depth of vibration was found to range between 15 and 55% of the total anatomical depth across all phonatory conditions. The nodal trajectories from the current study were compared qualitatively with the results from excised human hemi-larynx experiments published in Döllinger and Berry [(2006). J. Voice. 20(3), 401-413]. An estimate of the effective mass of a one-mass vocal fold model was also computed based on the effective depth of vibration observed in this study under various phonatory conditions.

    View details for DOI 10.1121/1.5091099

    View details for PubMedID 30823802

    View details for PubMedCentralID PMC6380906

  • Paired versus two-group experimental design for rheological studies of vocal fold tissues. Journal of biomechanics Xu, C. C., Li, D., Mau, T., McPherson, E., Du, M., Zhang, S. 2019; 83: 150-156

    Abstract

    Vibratory function of the vocal folds is largely determined by the rheological properties or viscoelastic shear properties of the vocal fold lamina propria. To date, investigation of the sample size estimation and statistical experimental design for vocal fold rheological studies is nonexistent. The current work provides the closed-form sample size formulas for two major study designs (i.e. paired and two-group designs) in vocal fold research. Our results demonstrated that the paired design could greatly increase the statistical power compared to the two-group design. By comparing the variance of estimated treatment effect, this study also confirms that ignoring within-subject and within-vocal fold correlations during rheological data analysis will likely increase type I errors. Finally, viscoelastic shear properties of intact and scarred rabbit vocal fold lamina propria were measured and used to illustrate theoretical findings in a realistic scenario and project sample size requirement for future studies.

    View details for DOI 10.1016/j.jbiomech.2018.11.040

    View details for PubMedID 30579579

  • Successful retrieval of a dislodged tracheoesophageal prosthesis distal to a neopharyngeal stricture Otolaryngology Case Reports Cleveland, P., Mau, T. 2019
  • Timing of Intervention for Unilateral Vocal Fold Paralysis Decision Making in Vocal Fold Paralysis: A Guide to Clinical Management Mau, T. 2019
  • Vocal Fold Lesion Case Studies in Otorhinolaryngology Head & Neck Surgery and Audiology: A Preparatory Review Mau, T., Childs, L. F. 2019
  • Spasmodic Dysphonia Case Studies in Otorhinolaryngology Head & Neck Surgery and Audiology: A Preparatory Review Childs, L. F., Mau, T. 2019
  • Vocal Fold Scar Laryngology: A Case-Based Approach Childs, L. F., Mau, T. 2019
  • Laryngeal Disorders: Benign Vocal Fold Pathologies The SAGE Encyclopedia of Human Communication Sciences and Disorders Mau, T., Kim, S. 2019
  • Individualized Patient Vocal Priorities for Tailored Therapy. Journal of speech, language, and hearing research : JSLHR Titze, I. R., Riede, T., Palaparthi, A., Hynan, L. S., Hamilton, A., Toles, L., Mau, T. 2018; 61 (12): 2884-2894

    Abstract

    The purposes of this study are to introduce the concept of vocal priorities based on acoustic correlates, to develop an instrument to determine these vocal priorities, and to analyze the pattern of vocal priorities in patients with voice disorders.Questions probing the importance of 5 vocal attributes (vocal clarity, loudness, mean speaking pitch, pitch range, vocal endurance) were generated from consensus conference involving speech-language pathologists, laryngologists, and voice scientists, as well as patient feedback. The responses to the preliminary items from 213 subjects were subjected to exploratory factor analysis, which confirmed 4 of the predefined domains. The final instrument consisted of a 16-item Vocal Priority Questionnaire probing the relative importance of clarity, loudness, mean speaking pitch, and pitch range.The Vocal Priority Questionnaire had high reliability (Cronbach's α = .824) and good construct validity. A majority of the cohort (61%) ranked vocal clarity as their highest vocal priority, and 20%, 12%, and 7% ranked loudness, mean speaking pitch, and pitch range, respectively, as their highest priority. The frequencies of the highest ranked priorities did not differ by voice diagnosis or by sex. Considerable individual variation in vocal priorities existed within these large trends.A patient's vocal priorities can be identified and taken into consideration in planning behavioral or surgical intervention for a voice disorder. Inclusion of vocal priorities in treatment planning empowers the patient in shared decision making, helps the clinician tailor treatment, and may also improve therapy compliance.

    View details for DOI 10.1044/2018_JSLHR-S-18-0109

    View details for PubMedID 30515514

    View details for PubMedCentralID PMC6440314

  • Articulation-to-Speech Synthesis Using Articulatory Flesh Point Sensors' Orientation Information Cao, B., Kim, M., Wang, J. R., van Santen, J., Mau, T., Wang, J., Int Speech Commun Assoc ISCA-INT SPEECH COMMUNICATION ASSOC. 2018: 3152-3156
  • Speaker-Independent Silent Speech Recognition from Flesh-Point Articulatory Movements Using an LSTM Neural Network. IEEE/ACM transactions on audio, speech, and language processing Kim, M., Cao, B., Mau, T., Wang, J. 2017; 25 (12): 2323-2336

    Abstract

    Silent speech recognition (SSR) converts non-audio information such as articulatory movements into text. SSR has the potential to enable persons with laryngectomy to communicate through natural spoken expression. Current SSR systems have largely relied on speaker-dependent recognition models. The high degree of variability in articulatory patterns across different speakers has been a barrier for developing effective speaker-independent SSR approaches. Speaker-independent SSR approaches, however, are critical for reducing the amount of training data required from each speaker. In this paper, we investigate speaker-independent SSR from the movements of flesh points on tongue and lip with articulatory normalization methods that reduce the inter-speaker variation. To minimize the across-speaker physiological differences of the articulators, we propose Procrustes matching-based articulatory normalization by removing locational, rotational, and scaling differences. To further normalize the articulatory data, we apply feature-space maximum likelihood linear regression and i-vector. In this paper, we adopt a bidirectional long short term memory recurrent neural network (BLSTM) as an articulatory model to effectively model the articulatory movements with long-range articulatory history. A silent speech data set with flesh points was collected using an electromagnetic articulograph (EMA) from twelve healthy and two laryngectomized English speakers. Experimental results showed the effectiveness of our speaker-independent SSR approaches on healthy as well as laryngectomy speakers. In addition, BLSTM outperformed standard deep neural network. The best performance was obtained by BLSTM with all the three normalization approaches combined.

    View details for DOI 10.1109/TASLP.2017.2758999

    View details for PubMedID 30271809

    View details for PubMedCentralID PMC6154510

  • Reducing sedation time for thyroplasty with arytenoid adduction with sequential anesthetic technique. The Laryngoscope Saadeh, C. K., Rosero, E. B., Joshi, G. P., Ozayar, E., Mau, T. 2017; 127 (12): 2813-2817

    Abstract

    To determine the extent to which a sequential anesthetic technique 1) shortens time under sedation for thyroplasty with arytenoid adduction (TP-AA), 2) affects the total operative time, and 3) changes the voice outcome compared to TP-AA performed entirely under sedation/analgesia.Case-control study.A new sequential anesthetic technique of performing most of the TP-AA surgery under general anesthesia (GA), followed by transition to sedation/analgesia (SA) for voice assessment, was developed to achieve smooth emergence from GA. Twenty-five TP-AA cases performed with the sequential GA-SA technique were compared with 25 TP-AA controls performed completely under sedation/analgesia. The primary outcome measure was the time under sedation. Voice improvement, as assessed by Consensus Auditory-Perceptual Evaluation of Voice, and total operative time were secondary outcome measures.With the conventional all-SA anesthetic, the duration of SA was 209 ± 26.3 minutes. With the sequential GA-SA technique, the duration of SA was 79.0 ± 18.9 minutes, a 62.3% reduction (P < 0.0001). There was no significant difference in the total operative time (209.5 vs. 200.9 minutes; P = 0.42) or in voice outcome. This sequential anesthetic technique has been easily adopted by multiple anesthesiologists and nurse anesthetists at our institution.TP-AA is effectively performed under sequential GA-SA technique with a significant reduction in the duration of time under sedation. This allows the surgeon to perform the technically more challenging part of the surgery under GA, without having to contend with variability in patient tolerance for laryngeal manipulation under sedation.3b. Laryngoscope, 127:2813-2817, 2017.

    View details for DOI 10.1002/lary.26743

    View details for PubMedID 28688211

  • The natural history of recoverable vocal fold paralysis: Implications for kinetics of reinnervation. The Laryngoscope Mau, T., Pan, H. M., Childs, L. F. 2017; 127 (11): 2585-2590

    Abstract

    Patients with unilateral vocal fold paralysis (UVFP) are commonly told to wait 12 months for spontaneous recovery. This study aims to 1) determine the time to vocal recovery in UVFP, 2) use that data to develop a neurophysiologically plausible model for recovery, and 3) use the model to generate meaningful predictions for patient counseling.Case series with de novo mathematical modeling.Patients with UVFP who could pinpoint a discrete onset of vocal improvement were identified. The time-to-recovery data were modeled by assuming an "early" recovery group with neuropraxia and a "late" recovery group with more severe nerve injury. For the late group, a two-stage model was developed to explain the time to recovery: regenerating axons must cross the site of injury in stage 1 (probabilistic), followed by unimpeded regrowth to the larynx in stage 2 (deterministic).Of 727 cases of UVFP over a 7-year period, 44 reported spontaneous recovery with a discrete onset of vocal improvement. A hybrid distribution incorporating the two stages (exponentially modified Gaussian) accurately modeled the time-to-recovery data (R2 = 0.918). The model predicts 86% of patients with recoverable UVFP will recover within 6 months, with 96% recovering within 9 months. Earlier vocal recovery is associated with recovery of vocal fold motion and younger age.Waiting 12 months for spontaneous recovery is probably too conservative. Repair across the site of injury, and not regrowth to larynx, is likely the rate-determining step in reinnervation, consistent with other works on peripheral nerve regeneration.4. Laryngoscope, 127:2585-2590, 2017.

    View details for DOI 10.1002/lary.26734

    View details for PubMedID 28608475

  • Factors Influencing Likelihood of Voice Therapy Attendance. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Misono, S., Marmor, S., Roy, N., Mau, T., Cohen, S. M. 2017; 156 (3): 518-524

    Abstract

    Objective To identify factors associated with the likelihood of attending voice therapy among patients referred for it in the CHEER (Creating Healthcare Excellence through Education and Research) practice-based research network infrastructure. Study Design Prospectively enrolled cross-sectional study. Setting CHEER network of community and academic sites. Methods Data were collected on patient-reported demographics, voice-related diagnoses, voice-related handicap (Voice Handicap Index-10), likelihood of attending voice therapy (VT), and opinions on factors influencing likelihood of attending VT. The relationships between patient characteristics/opinions and likelihood of attending VT were investigated. Results A total of 170 patients with various voice-related diagnoses reported receiving a recommendation for VT. Of those, 85% indicated that they were likely to attend it, regardless of voice-related handicap severity. The most common factors influencing likelihood of VT attendance were insurance/copay, relief that it was not cancer, and travel. Those who were not likely to attend VT identified, as important factors, unclear potential improvement, not understanding the purpose of therapy, and concern that it would be too hard. In multivariate analysis, factors associated with greater likelihood of attending VT included shorter travel distance, age (40-59 years), and being seen in an academic practice. Conclusions Most patients reported plans to attend VT as recommended. Patients who intended to attend VT reported different considerations in their decision making from those who did not plan to attend. These findings may inform patient counseling and efforts to increase access to voice care.

    View details for DOI 10.1177/0194599816679941

    View details for PubMedID 27879417

    View details for PubMedCentralID PMC5560903

  • A sequential anesthesia technique for surgical repair of unilateral vocal fold paralysis. Journal of anesthesia Rosero, E. B., Ozayar, E., Mau, T., Joshi, G. P. 2016; 30 (6): 1078-1081

    Abstract

    Thyroplasty with arytenoid adduction, a combined procedure for treatment of unilateral vocal fold paralysis, is typically performed under local anesthesia with sedation to allow for intraoperative voice assessment. However, the need for patient immobility and suppression of laryngeal responses to surgical manipulation can make sedation-analgesia challenging. We describe our first 26 consecutive cases undergoing thyroplasty and arytenoid adduction with a standardized technique consisting of a combination of general anesthesia with tracheal intubation followed by sedation-analgesia. Most patients (69 %) were women, with age of 53 ± 15 years (mean ± SD). Neck surgery was the cause of vocal fold paralysis in 50 % of patients. Initially, general anesthesia was maintained with desflurane and remifentanil with dexmedetomidine added just before tracheal extubation. During the sedation-analgesia phase, patients received infusions of remifentanil and dexmedetomidine. Duration of general anesthesia and sedation-analgesia phases was 162 ± 68.2 and 79 ± 18.3 min, respectively. Mean (SD) wake-up time was 8.0 ± 4.0 min after desflurane discontinuation. Extubation occurred without coughing, bucking, or agitation in 96 % of patients. All the patients were able to phonate appropriately and remained comfortable after emergence. This technique allowed improved surgical conditions with reduced patient discomfort and may be advantageous for other laryngeal and neck surgeries in which intraoperative patient feedback is required.

    View details for DOI 10.1007/s00540-016-2231-0

    View details for PubMedID 27522215

  • A Measure of the Auditory-perceptual Quality of Strain from Electroglottographic Analysis of Continuous Dysphonic Speech: Application to Adductor Spasmodic Dysphonia. Journal of voice : official journal of the Voice Foundation Somanath, K., Mau, T. 2016; 30 (6): 770.e9-770.e21

    Abstract

    (1) To develop an automated algorithm to analyze electroglottographic (EGG) signal in continuous dysphonic speech, and (2) to identify EGG waveform parameters that correlate with the auditory-perceptual quality of strain in the speech of patients with adductor spasmodic dysphonia (ADSD).Software development with application in a prospective controlled study.EGG was recorded from 12 normal speakers and 12 subjects with ADSD reading excerpts from the Rainbow Passage. Data were processed by a new algorithm developed with the specific goal of analyzing continuous dysphonic speech. The contact quotient, pulse width, a new parameter peak skew, and various contact closing slope quotient and contact opening slope quotient measures were extracted. EGG parameters were compared between normal and ADSD speech. Within the ADSD group, intra-subject comparison was also made between perceptually strained syllables and unstrained syllables.The opening slope quotient SO7525 distinguished strained syllables from unstrained syllables in continuous speech within individual subjects with ADSD. The standard deviations, but not the means, of contact quotient, EGGW50, peak skew, and SO7525 were different between normal and ADSD speakers. The strain-stress pattern in continuous speech can be visualized as color gradients based on the variation of EGG parameter values.EGG parameters may provide a within-subject measure of vocal strain and serve as a marker for treatment response. The addition of EGG to multidimensional assessment may lead to improved characterization of the voice disturbance in ADSD.

    View details for DOI 10.1016/j.jvoice.2015.11.005

    View details for PubMedID 26739857

    View details for PubMedCentralID PMC4925315

  • Recognizing Whispered Speech Produced by an Individual with Surgically Reconstructed Larynx Using Articulatory Movement Data. Workshop on Speech and Language Processing for Assistive Technologies Cao, B., Kim, M., Mau, T., Wang, J. 2016; 2016: 80-86

    Abstract

    Individuals with larynx (vocal folds) impaired have problems in controlling their glottal vibration, producing whispered speech with extreme hoarseness. Standard automatic speech recognition using only acoustic cues is typically ineffective for whispered speech because the corresponding spectral characteristics are distorted. Articulatory cues such as the tongue and lip motion may help in recognizing whispered speech since articulatory motion patterns are generally not affected. In this paper, we investigated whispered speech recognition for patients with reconstructed larynx using articulatory movement data. A data set with both acoustic and articulatory motion data was collected from a patient with surgically reconstructed larynx using an electromagnetic articulograph. Two speech recognition systems, Gaussian mixture model-hidden Markov model (GMM-HMM) and deep neural network-HMM (DNN-HMM), were used in the experiments. Experimental results showed adding either tongue or lip motion data to acoustic features such as mel-frequency cepstral coefficient (MFCC) significantly reduced the phone error rates on both speech recognition systems. Adding both tongue and lip data achieved the best performance.

    View details for DOI 10.21437/SLPAT.2016-14

    View details for PubMedID 29423453

    View details for PubMedCentralID PMC5800526

  • Nomenclature proposal to describe vocal fold motion impairment. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Rosen, C. A., Mau, T., Remacle, M., Hess, M., Eckel, H. E., Young, V. N., Hantzakos, A., Yung, K. C., Dikkers, F. G. 2016; 273 (8): 1995-9

    Abstract

    The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold impairment. Overarching terms of vocal fold immobility and hypomobility are rigorously defined. This includes assessment techniques and inclusion and exclusion criteria for determining vocal fold immobility and hypomobility. In addition, criteria for use of the following terms have been outlined in detail: vocal fold paralysis, vocal fold paresis, vocal fold immobility/hypomobility associated with mechanical impairment of the crico-arytenoid joint and vocal fold immobility/hypomobility related to laryngeal malignant disease. This represents the first rigorously defined vocal fold motion impairment nomenclature system. This provides detailed definitions to the terms vocal fold paralysis and vocal fold paresis.

    View details for DOI 10.1007/s00405-015-3663-0

    View details for PubMedID 26036851

    View details for PubMedCentralID PMC4930794

  • Multi-institutional Study of Voice Disorders and Voice Therapy Referral: Report from the CHEER Network. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Misono, S., Marmor, S., Roy, N., Mau, T., Cohen, S. M. 2016; 155 (1): 33-41

    Abstract

    To assess perspectives of patients with voice problems and identify factors associated with the likelihood of referral to voice therapy via the CHEER (Creating Healthcare Excellence through Education and Research) practice-based research network infrastructure.Prospectively enrolled cross-sectional study of CHEER patients seen for a voice problem (dysphonia).The CHEER network of community and academic sites.Patient-reported demographic information, nature and severity of voice problems, clinical diagnoses, and proposed treatment plans were collected. The relationship between patient factors and voice therapy referral was investigated.Patients (N = 249) were identified over 12 months from 10 sites comprising 30 otolaryngology physicians. The majority were women (68%) and white (82%). Most patients reported a recurrent voice problem (72%) and symptom duration >4 weeks (89%). The most commonly reported voice-related diagnoses were vocal strain, reflux, and benign vocal fold lesions. Sixty-seven percent of enrolled patients reported receiving a recommendation for voice therapy. After adjusting for sociodemographic and other factors, diagnoses including vocal strain/excessive tension and vocal fold paralysis and academic practice type were associated with increased likelihood of reporting a referral for voice therapy.The CHEER network successfully enrolled a representative sample of patients with dysphonia. Common diagnoses were vocal strain, reflux, and benign vocal fold lesions; commonly reported treatment recommendations included speech/voice therapy and antireflux medication. Recommendation for speech/voice therapy was associated with academic practice type.

    View details for DOI 10.1177/0194599816639244

    View details for PubMedID 27371624

    View details for PubMedCentralID PMC5370168

  • Predicting Achievable Fundamental Frequency Ranges in Vocalization Across Species. PLoS computational biology Titze, I., Riede, T., Mau, T. 2016; 12 (6): e1004907

    Abstract

    Vocal folds are used as sound sources in various species, but it is unknown how vocal fold morphologies are optimized for different acoustic objectives. Here we identify two main variables affecting range of vocal fold vibration frequency, namely vocal fold elongation and tissue fiber stress. A simple vibrating string model is used to predict fundamental frequency ranges across species of different vocal fold sizes. While average fundamental frequency is predominantly determined by vocal fold length (larynx size), range of fundamental frequency is facilitated by (1) laryngeal muscles that control elongation and by (2) nonlinearity in tissue fiber tension. One adaptation that would increase fundamental frequency range is greater freedom in joint rotation or gliding of two cartilages (thyroid and cricoid), so that vocal fold length change is maximized. Alternatively, tissue layers can develop to bear a disproportionate fiber tension (i.e., a ligament with high density collagen fibers), increasing the fundamental frequency range and thereby vocal versatility. The range of fundamental frequency across species is thus not simply one-dimensional, but can be conceptualized as the dependent variable in a multi-dimensional morphospace. In humans, this could allow for variations that could be clinically important for voice therapy and vocal fold repair. Alternative solutions could also have importance in vocal training for singing and other highly-skilled vocalizations.

    View details for DOI 10.1371/journal.pcbi.1004907

    View details for PubMedID 27309543

    View details for PubMedCentralID PMC4911068

  • Effect of resection depth of early glottic cancer on vocal outcome: an optimized finite element simulation. The Laryngoscope Mau, T., Palaparthi, A., Riede, T., Titze, I. R. 2015; 125 (8): 1892-9

    Abstract

    To test the hypothesis that subligamental cordectomy produces superior acoustic outcome than subepithelial cordectomy for early (T1-2) glottic cancer that requires complete removal of the superficial lamina propria but does not involve the vocal ligament.Computer simulation.A computational tool for vocal fold surgical planning and simulation (the National Center for Voice and Speech Phonosurgery Optimizer-Simulator) was used to evaluate the acoustic output of alternative vocal fold morphologies. Four morphologies were simulated: normal, subepithelial cordectomy, subligamental cordectomy, and transligamental cordectomy (partial ligament resection). The primary outcome measure was the range of fundamental frequency (F0 ) and sound pressure level (SPL). A more restricted F0 -SPL range was considered less favorable because of reduced acoustic possibilities given the same range of driving subglottic pressure and identical vocal fold posturing.Subligamental cordectomy generated solutions covering an F0 -SPL range 82% of normal for a rectangular vocal fold. In contrast, transligamental and subepithelial cordectomies produced significantly smaller F0 -SPL ranges, 57% and 19% of normal, respectively.This study illustrates the use of the Phonosurgery Optimizer-Simulator to test a specific hypothesis regarding the merits of two surgical alternatives. These simulation results provide theoretical support for vocal ligament excision with maximum muscle preservation when superficial lamina propria resection is necessary but the vocal ligament can be spared on oncological grounds. The resection of more tissue may paradoxically allow the eventual recovery of a better speaking voice, assuming glottal width is restored. Application of this conclusion to surgical practice will require confirmatory clinical data.N/A.

    View details for DOI 10.1002/lary.25267

    View details for PubMedID 26010240

    View details for PubMedCentralID PMC4512909

  • A randomized controlled trial of stretch-and-flow voice therapy for muscle tension dysphonia. The Laryngoscope Watts, C. R., Hamilton, A., Toles, L., Childs, L., Mau, T. 2015; 125 (6): 1420-5

    Abstract

    To investigate the effect of stretch-and-flow voice therapy on vocal function and handicap.Randomized controlled trial.Participants with primary muscle tension dysphonia were randomly assigned to experimental or control groups. Experimental participants received vocal hygiene education followed by 6 weeks of stretch-and-flow voice therapy. Control participants received vocal hygiene education only. Outcome variables consisted of a measure of vocal handicap (Voice Handicap Index [VHI]), maximum phonation time, s/z ratio, and acoustic measures. All measures were obtained at baseline prior to treatment and within 2 weeks posttreatment or at the end of the control period. The pre- to posttreatment measurement change (delta Δ) was applied to statistical analyses.A multivariate analysis of variance revealed significant group differences in pre-to-post changes on measures of VHI, maximum phonation time, and cepstral peak prominence (CPP) in connected speech and vowels (P = 0.003, 0.013, 0.025, and 0.017 respectively), with a significant reduction of VHI (Cohen's d = 1.6), increase in maximum phonation time (Cohen's d = 1.2), increase of CPP in connected speech (Cohen's d = 1.2), and increase of CPP in vowels (Cohen's d = 1.1) in the experimental group compared to the control group.This preliminary small sample randomized controlled trial found significantly greater improvement in vocal handicap, maximum phonation time, and acoustic measures of vocal function after participants received stretch-and-flow voice therapy compared to participants receiving vocal hygiene education alone. Additional research incorporating larger samples will be needed to confirm and further investigate these findings.1b.

    View details for DOI 10.1002/lary.25155

    View details for PubMedID 25641591

  • The effect of stretch-and-flow voice therapy on measures of vocal function and handicap. Journal of voice : official journal of the Voice Foundation Watts, C. R., Diviney, S. S., Hamilton, A., Toles, L., Childs, L., Mau, T. 2015; 29 (2): 191-9

    Abstract

    To investigate the efficacy of stretch-and-flow voice therapy as a primary physiological treatment for patients with hyperfunctional voice disorders.Prospective case series.Participants with a diagnosis of primary muscle tension dysphonia or phonotraumatic lesions due to hyperfunctional vocal behaviors were included. Participants received stretch-and-flow voice therapy structured once weekly for 6 weeks. Outcome variables consisted of two physiologic measures (s/z ratio and maximum phonation time), an acoustic measure (cepstral peak prominence [CPP]), and a measure of vocal handicap (voice handicap index [VHI]). All measures were obtained at baseline before treatment and within 2 weeks posttreatment.The s/z ratio, maximum phonation time, sentence CPP, and VHI showed statistically significant (P < 0.05) improvement through therapy. Effect sizes reflecting the magnitude of change were large for s/z ratio and VHI (d = 1.25 and 1.96 respectively), and moderate for maximum phonation time and sentence CPP (d = 0.79 and 0.74, respectively).This study provides supporting evidence for preliminary efficacy of stretch-and-flow voice therapy in a small sample of patients. The treatment effect was large or moderate for multiple outcome measures. The data provide justification for larger, controlled clinical trials on the application of stretch-and-flow voice therapy in the treatment of hyperfunctional voice disorders.

    View details for DOI 10.1016/j.jvoice.2014.05.008

    View details for PubMedID 25311595

  • Randomized controlled trial of supplemental augmentative and alternative communication versus voice rest alone after phonomicrosurgery. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Rousseau, B., Gutmann, M. L., Mau, T., Francis, D. O., Johnson, J. P., Novaleski, C. K., Vinson, K. N., Garrett, C. G. 2015; 152 (3): 494-500

    Abstract

    This randomized trial investigated voice rest and supplemental text-to-speech communication versus voice rest alone on visual analog scale measures of communication effectiveness and magnitude of voice use.Randomized clinical trial.Multicenter outpatient voice clinics.Thirty-seven patients undergoing phonomicrosurgery.Patients undergoing phonomicrosurgery were randomized to voice rest and supplemental text-to-speech communication or voice rest alone. The primary outcome measure was the impact of voice rest on ability to communicate effectively over a 7-day period. Pre- and postoperative magnitude of voice use was also measured as an observational outcome.Patients randomized to voice rest and supplemental text-to-speech communication reported higher median communication effectiveness on each postoperative day compared to those randomized to voice rest alone, with significantly higher median communication effectiveness on postoperative days 3 (P=.03) and 5 (P=.01). Magnitude of voice use did not differ on any preoperative (P>.05) or postoperative day (P>.05), nor did patients significantly decrease voice use as the surgery date approached (P>.05). However, there was a significant reduction in median voice use pre- to postoperatively across patients (P<.001) with median voice use ranging from 0 to 3 throughout the postoperative week.Supplemental text-to-speech communication increased patient-perceived communication effectiveness on postoperative days 3 and 5 over voice rest alone. With the prevalence of smartphones and the widespread use of text messaging, supplemental text-to-speech communication may provide an accessible and cost-effective communication option for patients on vocal restrictions.

    View details for DOI 10.1177/0194599814566601

    View details for PubMedID 25605690

    View details for PubMedCentralID PMC4617180

  • Relationship between patient-perceived vocal handicap and clinician-rated level of vocal dysfunction. The Laryngoscope Childs, L. F., Bielinski, C., Toles, L., Hamilton, A., Deane, J., Mau, T. 2015; 125 (1): 180-5

    Abstract

    The relationship between patient-reported vocal handicap and clinician-rated measures of vocal dysfunction is not understood. This study aimed to determine if a correlation exists between the Voice Handicap Index-10 (VHI-10) and the Voice Functional Communication Measure rating in the National Outcomes Measurement System (NOMS).Retrospective case series.Four hundred and nine voice evaluations over 12 months at a tertiary voice center were reviewed. The VHI-10 and NOMS scores, diagnoses, and potential comorbid factors were collected and analyzed.For the study population as a whole, there was a moderate negative correlation between the NOMS rating and the VHI-10 (Pearson r = -0.57). However, for a given NOMS level, there could be considerable spread in the VHI-10. In addition, as the NOMS decreased stepwise below level 4, there was a corresponding increase in the VHI-10. However, a similar trend in VHI-10 was not observed for NOMS above level 4, indicating the NOMS versus VHI-10 correlation was not linear. Among diagnostic groups, the strongest correlation was found for subjects with functional dysphonia. The NOMS versus VHI-10 correlation was not affected by gender or the coexistence of a psychiatric diagnosis.A simple relationship between VHI-10 and NOMS rating does not exist. Patients with mild vocal dysfunction have a less direct relationship between their NOMS ratings and the VHI-10. These findings provide insight into the interpretation of patient-perceived and clinician-rated measures of vocal function and may allow for better management of expectations and patient counseling in the treatment of voice disorders.

    View details for DOI 10.1002/lary.24889

    View details for PubMedID 25123059

  • Developing a Voice Practice Sataloff’s Comprehensive Textbook Of Otolaryngology Head and Neck Surgery Mau, T., Garrett, C. G. 2015
  • A rabbit vocal fold laser scarring model for testing lamina propria tissue-engineering therapies. The Laryngoscope Mau, T., Du, M., Xu, C. C. 2014; 124 (10): 2321-6

    Abstract

    To develop a vocal fold scarring model using an ablative laser in the rabbit as a platform for testing bioengineered therapies for missing or damaged lamina propria.Prospective controlled animal study.An optimal laser energy level was first determined by assessing the depths of vocal fold injury created by a Holmium:YAG laser at various energy levels on fresh cadaveric rabbit larynges. The selected energy level was then used to create controlled unilateral injuries in vocal folds of New Zealand white rabbits, with the contralateral folds serving as uninjured controls. After 4 weeks, the larynges were harvested and subjected to excised-larynx phonation with high-speed imaging and immunohistochemical staining for collagen types I and III, elastin, and hyaluronic acid (HA) with quantitative histological analysis.A total of 1.8 joules produced full-thickness injury of the lamina propria without extensive muscle injury. After 4 weeks, the injured vocal folds vibrated with reduced amplitude (P = 0.036) in excised-larynx phonation compared to normal vocal folds. The injured vocal folds contained a higher relative density of collagen type I (P = 0.004), higher elastin (P = 0.022), and lower HA (P = 0.030) compared to normal controls. Collagen type III was unchanged.With its potential for higher precision of injury, this laser vocal fold scarring model may serve as an alternative to scarring produced by cold instruments for studying the effects of vocal fold lamina propria bioengineered therapies.

    View details for DOI 10.1002/lary.24707

    View details for PubMedID 24715695

    View details for PubMedCentralID PMC4436966

  • Mucosa-associated lymphoid tissue (MALT) lymphoma presenting as subglottic stenosis: single-agent treatment using rituximab. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Bielinski, C., Luu, H. S., Mau, T. 2014; 150 (2): 334-5

    View details for DOI 10.1177/0194599813515632

    View details for PubMedID 24334958

  • Benign Lesions of the Larynx Total Otolaryngology Mau, T. 2014
  • Anatomy of the Male Voice Brothers, Sing On!: Conducting the Tenor-Bass Choir Mau, T., Childs, L. F., Hamilton, A., Palant, J. 2014
  • Ibid Bailey’s Head and Neck Surgery-Otolaryngology Kim, D. W., Mau, T. 2013
  • Modulating phonation through alteration of vocal fold medial surface contour. The Laryngoscope Mau, T., Muhlestein, J., Callahan, S., Chan, R. W. 2012; 122 (9): 2005-14

    Abstract

    1) To test whether alteration of the vocal fold medial surface contour can improve phonation and 2) to demonstrate that implant material properties affect vibration even when implantation is deep to the vocal fold lamina propria.Induced phonation of excised human larynges.Thirteen larynges were harvested within 24 hours postmortem. Phonation threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA). Small-volume injections (median, 0.0625 mL) were targeted to the inferomedial aspect of the thyroarytenoid muscle. Implant locations were assessed histologically.The effect of implantation on PTP was material dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP (Wilcoxon test, P = .00013 for onset). In contrast, the effect of implantation on PTF was similar, with both materials tending to decrease PTF (P = .16 for onset). Histology confirmed implant presence in the inferior half of the vocal fold vertical thickness.Taken together, these data suggested the implants may have altered the vocal fold medial surface contour, potentially resulting in a less convergent or more rectangular glottal geometry as a means to improve phonation. An implant with a closer viscoelastic match to vocal fold cover is desirable for this purpose, as material properties can affect vibration even when the implant is not placed within the lamina propria. This result is consistent with theoretical predictions and implies greater need for surgical precision in implant placement and care in material selection.

    View details for DOI 10.1002/lary.23451

    View details for PubMedID 22865592

    View details for PubMedCentralID PMC3461279

  • Three-dimensional morphometric analysis of cricoarytenoid subluxation. Journal of voice : official journal of the Voice Foundation Mau, T. 2012; 26 (2): 133-6

    Abstract

    To create a high-resolution three-dimensional (3D) reconstruction of a case of cricoarytenoid subluxation and perform quantitative analysis to understand its anatomy and functional consequence.Computational, with image processing and analysis.High-resolution axial computed tomography images of the larynx of a patient with an anteriorly subluxed arytenoid were processed with custom MATLAB routines to create a versatile 3D reconstruction. The geometries of the subluxed and nonsubluxed arytenoids were quantitatively compared.The anteriorly subluxed arytenoid has an inferoposteriorly displaced vocal process (VP), resulting in an elongated and inferiorly positioned vocal fold. The paradoxical posterior displacement of the VP with elongation of the vocal fold has not been described previously. Quantitative analysis reveals significant rotational components and a unidirectional translational component in anterior arytenoid subluxation.Quantitative 3D analysis yielded insight into the biomechanics of anterior arytenoid subluxation. Subluxation in this case appeared to involve more pure rotational than translational motion. Overrocking of the subluxed arytenoid can produce paradoxical elongation of the involved vocal fold.

    View details for DOI 10.1016/j.jvoice.2010.12.004

    View details for PubMedID 21550775

  • Phonation threshold pressure and flow in excised human larynges. The Laryngoscope Mau, T., Muhlestein, J., Callahan, S., Weinheimer, K. T., Chan, R. W. 2011; 121 (8): 1743-51

    Abstract

    To determine the phonation threshold pressure (PTP) and phonation threshold flow (PTF) in excised human larynges; determine the effects of posterior glottal width, glottal area, and gender on PTP and PTF; test the hypothesis that hysteresis is present in excised human laryngeal phonation; and compare these results to those from canine experiments and human subject measurements.Induced phonation of excised human larynges in the laboratory.Nine human larynges were harvested within 24 hours postmortem. PTP and PTF at phonation onset and offset were measured on a bench apparatus. The effects of posterior glottal width, glottal area, and gender were examined.Large intersubject variability was observed in PTP and PTF. PTP was comparable to those measured in vivo, whereas PTF was substantially higher. One-way ANOVA showed no significant dependence of PTP and PTF on posterior glottal width. Hysteresis was observed, with offset PTP and PTF lower than onset values. Offset measurements had significantly less variability than onset measurements (P = .012 for PTP, P = .0001 for PTF).This study is one of the first to report onset and offset PTP and PTF in fresh excised human larynges. The high PTF observed likely reflects a large direct current flow component due to vocal fold bowing. Offset PTP and PTF values may be intrinsically more reliably measured than onset values. The large intersubject variability in PTP and PTF may have implication for the clinical application of these aerodynamic parameters of phonation.

    View details for DOI 10.1002/lary.21880

    View details for PubMedID 21792964

    View details for PubMedCentralID PMC3146025

  • Rheometric properties of canine vocal fold tissues: variation with anatomic location. Auris, nasus, larynx Kimura, M., Mau, T., Chan, R. W. 2011; 38 (3): 367-72

    Abstract

    To evaluate the in vitro rheometric properties of the canine vocal fold lamina propria and muscle at phonatory frequencies, and their changes with anatomic location.Six canine larynges were harvested immediately postmortem. Viscoelastic shear properties of anterior, middle, and posterior portions of the vocal fold cover (lamina propria) as well as those of the medial thyroarytenoid (TA) muscle (vocalis muscle) were quantified by a linear, controlled-strain simple-shear rheometer. Measurements of elastic shear modulus (G') and dynamic viscosity (η') of the specimens were conducted with small-amplitude sinusoidal shear deformation over a frequency range of 1-250Hz.All specimens showed similar frequency dependence of the viscoelastic functions, with G' gradually increasing with frequency and η' decreasing with frequency monotonically. G' and η' of the canine vocalis muscle were significantly higher than those of the canine vocal fold cover, and η' of the canine vocal fold cover was significantly higher than that of the human vocal fold cover. There were no significant differences in G' and in η' between different portions of the canine vocal fold cover.These preliminary data based on the canine model suggested that the vocalis muscle, while in a relaxed state in vitro, is significantly stiffer and more viscous than the vocal fold cover during vibration at phonatory frequencies. For large-amplitude vocal fold vibration involving the medial portion of the TA muscle, such distinct differences in viscoelastic properties of different layers of the vocal fold should be taken into account in multi-layered biomechanical models of phonation.

    View details for DOI 10.1016/j.anl.2010.09.006

    View details for PubMedID 21035291

    View details for PubMedCentralID PMC3033979

  • Three-dimensional conformation of the injected bolus in vocal fold injections in a cadaver model. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Mau, T., Brewer, J. M., Gatzert, S. T., Courey, M. S. 2011; 144 (4): 552-7

    Abstract

    To determine the 3-dimensional (3D) conformation of the injected bolus in the larynx in vocal fold injections, to understand how the bolus interacts spatially with elements of the laryngeal framework, and to relate the above to clinical observations in performing vocal fold injections.Excised cadaveric larynx study.Laboratory.Vocal folds of 12 human excised cadaveric larynges were injected with calcium hydroxylapatite. High-resolution computed tomography scans were obtained of the injected larynges. Densities corresponding to the injected bolus and the laryngeal framework were extracted and processed with MATLAB routines to generate selective 3D reconstructions of the injected bolus within the laryngeal framework. Histology analysis was also performed to correlate with observations from the 3D reconstructions.Boluses injected into the lateral aspect of the thyroarytenoid muscle tended to be irregularly shaped, appeared to fill up the paraglottic space, and were associated with significant muscle compression. The vertical thickness of the injected boluses averaged 9.5 mm for lateral boluses and 7.6 mm for medial boluses, which were comparable to the vertical thickness of uninjected vocal folds.Laterally injected boluses are shaped by spatial constraints imposed by elements of the laryngeal framework. Compression of vocal fold muscle may be a mechanism accounting for stiffness from overinjection. The irregular shapes of some boluses may affect the outcome of subsequent medialization attempts. Injections may enhance the vocal fold contact height as a favorable effect beyond simple medialization.

    View details for DOI 10.1177/0194599810395107

    View details for PubMedID 21493234

    View details for PubMedCentralID PMC3110832

  • Three-dimensional arytenoid movement induced by vocal fold injections. The Laryngoscope Mau, T., Weinheimer, K. T. 2010; 120 (8): 1563-8

    Abstract

    To quantitatively characterize arytenoid movement induced by vocal fold injection augmentation in an excised larynx model.: Laboratory and computational.Vocal folds of human cadaveric larynges were injected with calcium hydroxylapatite. High-resolution computed tomography scans were obtained before and after injection. Densities corresponding to the arytenoid and cricoid cartilages were extracted and processed with custom MATLAB routines to generate selective three-dimensional reconstructions of the larynx. Pre- and postinjection positions of the arytenoid were compared.Vocal fold injections resulted in predominantly small-magnitude medial rotation and medial translation of the arytenoid. Movements in other directions as would be expected in physiologic adduction were not observed.Vocal fold injection augmentation induced passive movement of the arytenoid that has not been described previously. This movement does not reproduce the trajectory of physiologic adduction. This finding has implications for the treatment of unilateral vocal fold paralysis without arytenoid repositioning maneuvers.

    View details for DOI 10.1002/lary.20973

    View details for PubMedID 20564669

  • Factors associated with voice therapy outcomes in the treatment of presbyphonia. The Laryngoscope Mau, T., Jacobson, B. H., Garrett, C. G. 2010; 120 (6): 1181-7

    Abstract

    Age, vocal fold atrophy, glottic closure pattern, and the burden of medical problems are associated with voice therapy outcomes for presbyphonia.Retrospective.Records of patients seen over a 3-year period at a voice center were screened. Inclusion criteria consisted of age over 55 years, primary complaint of hoarseness, presence of vocal fold atrophy on examination, and absence of laryngeal or neurological pathology. Videostroboscopic examinations on initial presentation were reviewed. Voice therapy outcomes were assessed with the American Speech-Language-Hearing Association National Outcomes Measurement System scale. Statistical analysis was performed with Spearman rank correlation and chi(2) tests.Sixty-seven patients were included in the study. Of the patients, 85% demonstrated improvement with voice therapy. The most common type of glottic closure consisted of a slit gap. Gender or age had no effect on voice therapy outcomes. Larger glottic gaps on initial stroboscopy examination and more pronounced vocal fold atrophy were weakly correlated with less improvement from voice therapy. A weak correlation was also found between the number of chronic medical conditions and poorer outcomes from voice therapy.The degree of clinician-determined improvement in vocal function from voice therapy is independent of patient age but is influenced by the degree of vocal fold atrophy, glottic closure pattern, and the patient's burden of medical problems.

    View details for DOI 10.1002/lary.20890

    View details for PubMedID 20513037

  • Viscoelastic properties of phonosurgical biomaterials at phonatory frequencies. The Laryngoscope Kimura, M., Mau, T., Chan, R. W. 2010; 120 (4): 764-8

    Abstract

    The purpose of this study was to examine the functional biomechanical properties of several injectable biomaterials currently or potentially used for vocal fold augmentation.Rheometric investigation of phonosurgical materials in vitro.Linear viscoelastic shear properties of 3% bovine collagen (atelocollagen), micronized AlloDerm (Cymetra; LifeCell Corp., Branchburg, NJ), calcium hydroxylapatite (CaHA) (Radiesse; BioForm Medical, San Mateo, CA), and 2.4% cross-linked hyaluronic acid (HA) gel (Juvéderm; Allergan, Inc., Irvine, CA) were quantified as functions of frequency covering the phonatory range, and compared to those of the human vocal fold cover. Measurements of elastic shear modulus (G') and dynamic viscosity (eta') were made at up to 250 Hz with a controlled-strain simple-shear rheometer. Linear least-squares regression was conducted to curve-fit log G' and log eta' versus log frequency, and statistical analysis was performed with one-way analysis of variance.Radiesse and Cymetra were found to be the stiffest and the most viscous materials, followed by Juvéderm and atelocollagen. There were significant differences in the magnitudes of G' and eta' among the phonosurgical materials and the normal human vocal fold cover (p < .001), whereas there was no significant difference in the frequency dependence of G' and eta' among the materials. Post hoc Tukey tests revealed significant differences (p < .05) in pairwise comparisons of the magnitudes of G' and eta' among all materials and the vocal fold cover.These findings suggested that although these biomaterials may be injected lateral to the lamina propria for the treatment of glottic insufficiency, none of them are rheologically optimal for the functional reconstruction of the vocal fold lamina propria.

    View details for DOI 10.1002/lary.20816

    View details for PubMedID 20213661

    View details for PubMedCentralID PMC2919825

  • Diagnostic Evaluation and Management of Hoarseness Medical Clinics of North America Mau, T. 2010
  • Globus Extraesophageal Reflux Mau, T., Ekbom, D. C., Garrett, C. G. 2009
  • Influence of gender and injection site on vocal fold augmentation. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Mau, T., Courey, M. S. 2008; 138 (2): 221-5

    Abstract

    To determine the influence of gender and injection site on the amount of injectate needed to medialize an immobile vocal fold, and to describe the distribution patterns of the injected bolus.Surgical intervention in human cadaveric larynges in experimental setting.Cadaveric larynges were injected with calcium hydroxylapatite into the lateral or medial aspect of the vocal fold. High-resolution CT scans were obtained before and after injection.Males required 50% to 60% more material than females (P = 0.03). For both genders, lateral injections required more than medial injections (P < 0.001). Laterally injected boluses tended to distribute toward the cricothyroid space, with frank extrusions more common in females.The amount of injectate required to medialize male and female vocal folds is significantly different. The smaller size of the female larynx likely accounts for a higher incidence of extrusion through the cricothyroid space. These gender differences should be taken into consideration when performing injection laryngoplasty.

    View details for DOI 10.1016/j.otohns.2007.10.028

    View details for PubMedID 18241720

  • Cadaveric and engineering analysis of the septal L-strut. The Laryngoscope Mau, T., Mau, S. T., Kim, D. W. 2007; 117 (11): 1902-6

    Abstract

    To identify patterns of failure of the L-strut, to identify elements of the nasal framework that support the L-strut, and to investigate the effect of altering L-strut design on its stability.Laboratory study with human cadaveric heads and computational modeling.Directional forces were applied to cadaveric L-struts and patterns of failure with incremental force were noted. Computational modeling using the finite element method (FEM) was employed to determine quantitatively the effect of various modifications on the stability of the L-strut.The L-strut was found to respond to frontal force initially by buckling. This buckling was reversible until the force exceeded a certain threshold when the L-strut broke at the bony-cartilaginous junction. The threshold force varied depending on the length of the overlap with the bony vault. Intact mucoperichondrium provided significant stability. Modeling with FEM showed that the preservation of a triangular piece of cartilage at the dorsal anchor of a narrowed L-strut can offset some of the loss in mechanical stability.Intrinsic elasticity of the septal cartilage, the mucoperichondrial flap, and overlap with the bony vault all contribute to the stability of the L-strut, which is enhanced by preserving a small segment of cartilage at the bony-cartilaginous junction of the dorsal L-strut.

    View details for DOI 10.1097/MLG.0b013e3181255ec4

    View details for PubMedID 17721403

  • Minicricothyrotomy approach with fiberoptic guidance for management of posterior glottic stenosis. The Laryngoscope Mau, T., Pletcher, S. D., Cavanagh, P. W., Courey, M. S., Wang, S. J. 2007; 117 (8): 1488-90

    View details for DOI 10.1097/MLG.0b013e318063e88c

    View details for PubMedID 17762272

  • Complete bony syngnathia: Report of a case and review. Archives of otolaryngology--head & neck surgery Trigg, D. J., Mau, I. T., Rosbe, K. W. 2007; 133 (2): 187-90

    View details for DOI 10.1001/archotol.133.2.187

    View details for PubMedID 17309989

  • Surgical Anatomy of the Nose Head and Neck Surgery-Otolaryngology Kim, D. W., Mau, T. 2006
  • Voice and Speech Abnormalities in Systemic Neurodegenerative Disorders Textbook of Laryngology Mau, T., Courey, M. S. 2006
  • Management of cervical metastases in advanced squamous cell carcinoma of the tonsillar fossa following radiotherapy. Archives of otolaryngology--head & neck surgery Mau, T., Oh, Y., Bucci, M. K., Eisele, D. W. 2005; 131 (7): 600-4

    Abstract

    To assess the value of planned neck dissection in patients with a complete response to definitive radiotherapy for squamous cell carcinoma of the tonsillar fossa with advanced nodal disease.Case series.Academic tertiary care medical center.A consecutive series of 36 patients with squamous cell carcinoma of the tonsillar fossa with N2 or N3 nodal disease treated with primary radiation therapy with or without concurrent chemotherapy between January 1, 1992, and April 1, 2003, at the University of California, San Francisco, Comprehensive Cancer Center. Patients treated with primary surgery, those treated with palliative intent, or those with preexisting malignancies were excluded.Regional control and overall survival.Of the study group, 15 patients (42%) achieved a complete response, 17 (47%) achieved a partial response, and 1 (3%) was a nonresponder. The response in 3 patients (8%) could not be assessed. Of the 15 patients with a complete response, only 2 (13%) later developed regional recurrences, 1 of which was an isolated recurrence in the neck. Regional control and overall survival at 3 years were 78% and 48%, respectively.The rate of regional recurrence after a complete response to radiation therapy with or without concurrent chemotherapy for tonsillar squamous cell carcinoma with advanced cervical metastases is low. Our results support close surveillance of the neck in those who have achieved a complete response after radiation therapy with or without chemotherapy.

    View details for DOI 10.1001/archotol.131.7.600

    View details for PubMedID 16027282

  • The pro region N-terminal domain provides specific interactions required for catalysis of alpha-lytic protease folding. Biochemistry Cunningham, E. L., Mau, T., Truhlar, S. M., Agard, D. A. 2002; 41 (28): 8860-7

    Abstract

    The extracellular bacterial protease, alpha-lytic protease (alphaLP), is synthesized with a large, two-domain pro region (Pro) that catalyzes the folding of the protease to its native conformation. In the absence of its Pro folding catalyst, alphaLP encounters a very large folding barrier (DeltaG = 30 kcal mol(-1)) that effectively prevents the protease from folding (t(1/2) of folding = 1800 years). Although homology data, mutational studies, and structural analysis of the Pro.alphaLP complex suggested that the Pro C-terminal domain (Pro C-domain) serves as the minimum "foldase" unit responsible for folding catalysis, we find that the Pro N-terminal domain (Pro N-domain) is absolutely required for alphaLP folding. Detailed kinetic analysis of Pro N-domain point mutants and a complete N-domain deletion reveal that the Pro N-domain both provides direct interactions with alphaLP that stabilize the folding transition state and confers stability to the Pro C-domain. The Pro N- and C-domains make conflicting demands upon native alphaLP binding that are alleviated in the optimized interface of the folding transition state complex. From these studies, it appears that the extremely high alphaLP folding barrier necessitates the presence of both the Pro domains; however, alphaLP homologues with less demanding folding barriers may not require both domains, thus possibly explaining the wide variation in the pro region size of related pro-proteases.

    View details for DOI 10.1021/bi020214o

    View details for PubMedID 12102628

  • Partitioning roles of side chains in affinity, orientation, and catalysis with structures for mutant complexes: asparagine-229 in thymidylate synthase. Biochemistry Finer-Moore, J. S., Liu, L., Schafmeister, C. E., Birdsall, D. L., Mau, T., Santi, D. V., Stroud, R. M. 1996; 35 (16): 5125-36

    Abstract

    Thymidylate synthase (TS) methylates only dUMP, not dCMP. The crystal structure of TS.dCMP shows sCMP 4-NH2 excluded from the space between Asn-229 and His-199 by the hydrogen bonding and steric properties and Asn-229. Consequently, 6-C of dCMP is over 4 A from the active site sulfhydryl. The Asn-229 side chain is prevented from flipping 180 degrees to and orientation the could hydrogen bond to dCMP by a hydrogen bond network between conserved residues. Thus, the specific binding of dUMP by TS results from occlusion of competing substrates by steric and electronic effects of residues in the active site cavity. When Asn-229 is replaced by a cysteine, the Cys-229 S gamma rotates out of the active site, and the mutant enzyme binds both dCMP and dUMP tightly but does not methylate dCMP. Thus simply admitting dCMP into the dUMP binding site of TS is not sufficient for methylation of dCMP. Structures of nucleotide complexes of TS N229D provide a reasonable explanation for the preferential methylation of dCMP instead of dUMP by this mutant. In TS N229D.dCMP, Asp-229 forms hydrogen bonds to 3-N and 40NH2 of dCMP. Neither the Asp-229 carboxyl moiety nor ordered water appears to hydrogen bond to 4-O of dUMP. Hydrogen bonds to 4-O (or 4-NH2) have been proposed to stabilize reaction intermediates. If their absence in TS N229D.dUMP persists in the ternary complex, it could explain the 10(4)-fold decrease in kcat/Km for dUMP.

    View details for DOI 10.1021/bi952751x

    View details for PubMedID 8611496

  • Salt bridge relay triggers defective LDL receptor binding by a mutant apolipoprotein. Structure (London, England : 1993) Wilson, C., Mau, T., Weisgraber, K. H., Wardell, M. R., Mahley, R. W., Agard, D. A. 1994; 2 (8): 713-8

    Abstract

    Apolipoprotein-E (apo-E), a 34kDa blood plasma protein, plays a key role in directing cholesterol transport via its interaction with the low density lipoprotein (LDL) receptor. The amino-terminal domain of apo-E forms an unusually elongated four-helix bundle arranged such that key basic residues involved in LDL receptor binding form a cluster at the end of one of the helices. A common apo-E variant, apo-E2, corresponding to the single-site substitution Arg158-->Cys, displays minimal LDL receptor binding and is associated with significant changes in plasma cholesterol levels and increased risk of coronary heart disease. Surprisingly, the site of mutation in this variant is physically well removed (> 12A) from the cluster of LDL receptor binding residues.We now report the refined crystal structure of the amino-terminal domain of apo-E2, at a nominal resolution of 3.0A. This structure reveals significant conformational changes relative to the wild-type protein that may account for reduced LDL receptor binding. Removal of the Arg158 side chain directly disrupts a pair of salt bridges, causing a compensatory reorganization of salt bridge partners that dramatically alters the charge surface presented by apo-E to its receptor.It is proposed that the observed reorganization of surface salt bridges is responsible for the decreased receptor binding by apo-E2. This reorganization, essentially functioning as a mutationally induced electrostatic switch to turn off receptor binding, represents a novel mechanism for the propagation of conformational changes over significant distances.

    View details for DOI 10.1016/s0969-2126(00)00072-1

    View details for PubMedID 7994571

  • Recognition of DNA by GAL4 in solution: use of a monomeric protein-DNA complex for study by NMR. Biochemistry Baleja, J. D., Mau, T., Wagner, G. 1994; 33 (10): 3071-8

    Abstract

    The complex of a monomer of GAL4 with DNA has been investigated by two-dimensional 1H nuclear magnetic resonance (NMR) spectroscopy. Previous X-ray analysis has revealed a structure in which a dimer of the N-terminal 65-residue fragment of GAL4 forms a complex, 27 kDa in molecular mass, with a 19 base pair full-binding-site DNA [Marmorstein, R., Carey, M., Ptashne, M., & Harrison, S. C. (1992) Nature 356, 408-414]. We have developed a smaller system, half in molecular mass, which is amenable for detailed analysis using NMR. Titration of a 10 base pair half-binding-site DNA with GAL4-(65) shows 1:1 binding, illustrating that one monomer of the protein binds in a specific manner to half-site DNA. The components of the protein-DNA complex are mainly in fast exchange on the NMR chemical shift time scale, with an equilibrium dissociation constant of 161 +/- 12 microM. With a basis of chemical shift data for free GAL4 protein and for the free half-site DNA, the fast exchange facilitates 1H resonance assignments in the complex since cross-peak positions can be examined at different protein:DNA ratios. Chemical shift changes in the DNA reveal the base pairs that are important for recognition by GAL4. Intermolecular NOE cross-peaks are also observed in spectra of the protein-DNA complex. Their identification places the C-terminal end of the first alpha-helix (residues 12-17) in a position such that the amino acids are able to read the DNA sequence in a manner entirely consistent with the X-ray structure of the related complex.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for DOI 10.1021/bi00176a041

    View details for PubMedID 8130221

  • Effects of DNA binding and metal substitution on the dynamics of the GAL4 DNA-binding domain as studied by amide proton exchange. Protein science : a publication of the Protein Society Mau, T., Baleja, J. D., Wagner, G. 1992; 1 (11): 1403-12

    Abstract

    Backbone amide proton exchange rates in the DNA-binding domain of GAL4 have been determined using 1H-15N heteronuclear correlation NMR spectroscopy. Three forms of the protein were studied-the native Zn-containing protein, the Cd-substituted protein, and a Zn-GAL4/DNA complex. Exchange rates in the Zn-containing protein are significantly slower than in the Cd-substituted protein. This shows that Cd-substituted GAL4 is destabilized relative to the native Zn-containing protein. Upon DNA binding, global retardation of amide proton exchange with solvent was observed, indicating that internal fluctuations of the DNA-recognition module are significantly reduced by the presence of DNA. In all forms of the protein, the internal dyad symmetry of the DNA-recognition module of GAL4 is reflected by the backbone amide proton exchange rates.

    View details for DOI 10.1002/pro.5560011102

    View details for PubMedID 1303761

    View details for PubMedCentralID PMC2142116