Modification of velopharyngeal closure pressures during phonation by neuromuscular electrical stimulation in healthy individuals.

Introduction: Rhinophonia aperta may result from velopharyngeal insufficiency. Neuromuscular electrical stimulation (NMES) has been discussed in the context of muscle strengthening. The aim of this study was to evaluate in healthy subjects whether NMES can change the velopharyngeal closure pattern during phonation and increase muscle strength. Method: Eleven healthy adult volunteers (21-57 years) were included. Pressure profiles were measured by high resolution manometry (HRM): isolated sustained articulation of /a/ over 5 s (protocol 1), isolated NMES applied to soft palate above motor threshold (protocol 2) and combined articulation with NMES (protocol 3). Mean activation pressures (MeanAct), maximum pressures (Max), Area under curve (AUC) and type of velum reactions were compared. A statistical comparison of mean values of protocol 1 versus protocol 3 was carried out using the Wilcoxon signed rank test. Ordinally scaled parameters were analyzed by cross table. Results: MeanAct values measured: 17.15±20.69 mmHg (protocol 1), 34.59±25.75 mmHg (protocol 3) on average, Max: 37.86±49.17 mmHg (protocol 1), 87.24±59.53 mmHg (protocol 3) and AUC: 17.06±20.70 mmHg.s (protocol 1), 33.76±23.81 mmHg.s (protocol 3). Protocol 2 produced velum reactions on 32 occasions. These presented with MeanAct values of 13.58±12.40 mmHg, Max values of 56.14±53.14 mmHg and AUC values of 13.84±12.78 mmHg.s on average. Statistical analysis comparing protocol 1 and 3 showed more positive ranks for MeanAct, Max and AUC. This difference reached statistical significance (p=0.026) for maximum pressure values. Conclusions: NMES in combination with articulation results in a change of the velopharyngeal closure pattern with a pressure increase of around 200% in healthy individuals. This might be of therapeutic benefit for patients with velopharyngeal insufficiency.

Differences in velopharyngeal pressures during speech sound production in patients with unilateral cleft lip and palate (UCLP) and healthy individuals.

Background: During articulation the velopharynx needs to be opened and closed rapidly and a tight closure is needed. Based on the hypothesis that patients with cleft lip and palate (CLP) produce lower pressures in the velopharynx than healthy individuals, this study compared pressure profiles of the velopharyngeal closure during articulation of different sounds between healthy participants and patients with surgically closed unilateral CLP (UCLP) using high resolution manometry (HRM). Materials and methods: Ten healthy adult volunteers (group 1: 20-25.5 years) and ten patients with a non-syndromic surgically reconstructed UCLP (group 2: 19.1-26.9 years) were included in this study. Pressure profiles during the articulation of four sounds (/i:/, /s/, /ʃ/ and /n/) were measured by HRM. Maximum, minimum and average pressures, time intervals as well as detection of a previously described 3-phase-model were compared. Results: Both groups presented with similar pressure curves for each phoneme with regards to the phases described and pressure peaks, but differed in total pressures. An exception was noted for the sound /i:/, where a 3-phase-model could not be seen for most patients with UCLP. Differences in velopharynx pressures of 50% and more were found between the two groups. Maximum and average pressures in the production of the alveolar fricative reached statistical significance. Conclusions: It can be concluded that velopharyngeal pressures of patients with UCLP are not sufficient to eliminate nasal resonance or turbulence during articulation, especially for more complex sounds. These results support a general understanding of hypernasality during speech implying a (relative) velopharyngeal insufficiency.

[Prevalence of mucosal injuries during flexible endoscopic evaluation of swallowing in the presence of a nasogastric tube]. / Prävalenz von Schleimhautläsionen bei Durchführung der transnasalen endoskopischen Dysphagiediagnostik und angelegter Nasogastralsonde.

BACKGROUND: The flexible endoscopic evaluation of swallowing (FEES) is an established low-risk examination method to assess the risk of penetration or aspiration in patients with dysphagia. FEES might be more difficult or of higher-risk when a nasogastric tube is in place. OBJECTIVE: This study aims to identify whether the prevalence of mucosal lesions is higher when the endoscopy is carried out with a nasogastric tube in place. Pre-existing mucosal lesions were also documented. METHODS: In a retrospective, monocentric study, a total of 918 FEES procedures routinely performed in hospitalized patients of a university hospital from January 2014 to March 2019 were evaluated. Mucosal lesions were identified and characterized for descriptive statistics. RESULTS: In the video material analysed here, no endoscopy-related injuries were identified. However, pre-existing mucosal lesions, which often occurred as multiple lesions, were detected in 48.6% of the endoscopies. Further analysis showed that these pre-existing lesions were not worsened by the endoscopy performed. CONCLUSION: The results demonstrate that transnasal flexible endoscopy is a safe, low-risk examination method, even in patients with a nasogastric tube. A very high number of pre-existing mucosal lesions were found, which is probably related to the previous insertion of the nasogastric tube. Due to the high number of pre-existing lesions, strategies should be developed to minimize injuries when placing nasogastric tubes.

Phonation-induced Upper Esophageal Sphincter Contraction Caused by Different Phonation Types.

INTRODUCTION: The upper esophageal sphincter (UES) has been reported to show activity during phonation. As it is still unknown whether the phonation-induced UES contraction represents a reflex or a simultaneous activation phenomenon, i.e. co-innervation, this study aims to investigate and characterize the phonation-induced contraction of the UES in healthy individuals by analyzing the influence of various phonation tasks on pressure parameters of the UES. METHODS: Twenty-five healthy volunteers produced the German neutral vowel [ə] in five different phonation tasks (modal voice, whispering, voiceless speech, creaky voice, and whispery voice). Simultaneously, they underwent high resolution manometry and electroglottography for measurement of pressure parameters in the region of the UES and latencies between larynx and UES activation. RESULTS: During all types of phonation, the maximum pressures of the UES increased significantly (maximum pressure increases of 72%-132%). With regard to mean pressures this was valid for modal voice and whispering (mean pressure increases of 20%-25%). Differences concerning total pressure changes reached statistical significance when comparing whispering and voiceless speech as well as whispery voice. However, differences concerning the total pressure change between modal voices on the one hand and voiceless speech and whispery voice on the other hand turned out to be small. The averaged time delay between larynx and UES activation ranged from approximately -15 ms (whispery voice) to +15 ms (whispering). CONCLUSION: A phonation induced pressure increase of the UES was confirmed in this study and did exist for different types of phonation. The extent of total pressure changes in the UES increases in relation with laryngeal muscle activity necessary for the phonation type. Next to varying effects of different types of phonation on UES activation, very short latencies indicate that a phonation induced contraction of the UES exists most likely due to co-innervation of UES and laryngeal muscles by the vagus nerve.

Studying effects of neuromuscular electrostimulation therapy in patients with dysphagia: which pitfalls may occur? A translational phase I study.

Background: Previous results of clinical studies suggest that neuromuscular electrostimulation (NMES) therapy, especially in combination with traditional dysphagia therapy, may be helpful in patients with neurogenic swallowing disorders. In these studies, repetitive application of a rectangular current impulse was used to increase muscle strength of the anterior neck. However, according to sports physiological findings, an increase of muscle strength can be better achieved by using different NMES stimulation protocols, e.g. KOTS. The aim of the translational investigator-initiated, non-commercial pilot study presented here was to provide data and insights for the planning of subsequent phase II and III studies on the effectiveness of such stimulation protocols in dysphagia therapy. Methods: 30 post-stroke patients with oropharyngeal dysphagia were included in this prospective pilot study and randomly allocated to either neuromuscular electrostimulation (NMES) or sham stimulation in combination with traditional dysphagia therapy (TDT), a pre- and post-therapeutic fiberoptic-endoscopic evaluation of swallowing (FEES) with the Dysphagia Outcome and Severity Scale (DOSS) (primary outcome measure), Secretion Scale by Murray, Penetration and Aspiration Scale (PAS) and throat clearance (TC) abilities. Recruitment rate, interrater comparison and number of relevant adverse events were recorded as metadata. Results: Despite a recruiting time of over 24 months, only twelve patients could be included. Moreover, clinical data indicated a significant variance of clinical pictures. Significant differences in verum versus sham therapy were not observed. DOSS values in both study groups showed general improvements at the end of the trial. Interrater reliability was low. No adverse events were reported. Discussion: When planning further dysphagia therapy studies, it must be taken into account that it can be problematic to recruit sufficiently large study collectives within an appropriate study period. This is especially important since a possible additional benefit of NMES to TDT is probably rather small or may only occur in certain deficit constellations. The low interrater reliability observed here must be improved by appropriate training measures. Fortunately, no relevant undesirable side effects occurred. This could have a positive effect on the acceptance of volunteers to participate in the study.

Effect of Capsaicinoids on Neurophysiological, Biochemical, and Mechanical Parameters of Swallowing Function.

Oropharyngeal dysphagia is prevalent in age-related neurological disorders presenting with impaired efficacy and safety of swallowing due to a loss of muscle force and sensory deficits. Stimulating the oropharynx with capsaicin that mediates Substance P release is an emerging pharmacological treatment option which needs further scientific evidence. Our aim was to comprehensively evaluate the effect of capsaicin on biochemical, neurophysiological, and biomechanical parameters of swallowing function. In a randomized study on healthy individuals, the impact of orally administered capsaicinoids at different dosages and application durations in comparison to non-carbonated water was evaluated. Time course and magnitude of salivary Substance P increase were monitored. Magnetoencephalography was used to detect cortical swallowing network alterations. Modifications in swallowing biomechanics were measured applying high-resolution pharyngeal manometry. Capsaicinoids at 10 µmol/L improved swallowing efficacy as seen by a significant increase of pharyngeal contractile integral and upper esophageal sphincter activation and relaxation times in manometry. Significant improvement of precision in a challenging swallow task accompanied by a reduction in swallowing-related submental electromyographic power was observed with capsaicinoids preconditioning at 10 µmol/L over 5 min, but not with continuous stimulation. The cortical activation pattern remained unchanged after any intervention. A significant increase of salivary Substance P was not detected with 10 µmol/L but with 50 µmol/L and lasted for 15 min after application. Capsaicinoids mediate dose-dependent Substance P release and positively alter swallowing biomechanics in healthy subjects. The results provide supportive evidence for the value of natural capsaicinoids to improve swallowing function.

Upper Esophageal Sphincter Response to Laryngeal Adductor Reflex Elicitation in Humans.

OBJECTIVE: The laryngeal adductor reflex (LAR) is an important mechanism to secure the airways from potential foreign body aspiration. An involvement of the upper esophageal sphincter (UES) in terms of a laryngo-UES contractile reflex has been identified after laryngeal mucosa stimulation. However, the LAR-UES relationship has not yet been fully explained. This study aimed to determine the magnitude, latency, and occurrence rate of the UES pressure response when the LAR is triggered in order to elucidate the functional relationship between the larynx and the UES. METHODS: This prospective study included seven healthy volunteers (5 female, 2 male, age 22-34 years). Laryngeal penetration was simulated by eliciting the LAR 20 times in each individual by applying water-based microdroplets onto the laryngeal mucosa. UES pressures were measured simultaneously using high-resolution manometry. RESULTS: Two distinct pressure phases (P1, P2) associated with the LAR were identified. P1 corresponded with a short-term UES pressure decrease in two subjects and a pressure increase in five subjects occurring 200 to 500 ms after the stimulus. In P2, all subjects experienced an increase in UES pressure with a latency time of approximately 800 to 1700 ms and an average of 40 to 90 mmHg above the UES resting tone. CONCLUSION: Foreign bodies penetrating the laryngeal inlet lead to a reflex contraction of the UES. Phase P1 could be a result of vocal fold activity caused by the LAR, leading to pressure changes in the UES. The constriction during P2 could strengthen the barrier function of the UES in preparation to a subsequent cough that may be triggered to clear the airways. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1778-E1784, 2021.

Influence of Acid Swallows on the Dynamics of the Upper Esophageal Sphincter.

Mechanisms of the upper esophageal sphincter (UES) when exposed to acid are still incompletely understood. The presented work investigated the reaction of the UES to acid exposure during swallowing. Ten healthy individuals swallowed ten 2 ml neutral water boli of pH 7, followed by 10 swallows each of different levels of acidity (pH 1.8, pH 3 and pH 5). Effects were analyzed by high-resolution manometry (HRM) for the primary parameter Restitution Time, as well as Resting Pressures, maximal, minimal pressures and time intervals. Restitution Times measured mean values of 12.67 s (SD ± 7.03 s) for pH 1.8, pH 7 = 8.69 s (SD ± 2.72 s), pH 3 = 7.56 s (SD ± 2.23 s) and pH 5 = 7.29 s (SD ± 2.55 s), showing prolonged Restitution Times in the UES when exposed to strong bolus acidity. This difference was significant towards the neutral bolus, but also to less acidic boli (pH 5: p = 0.006, pH 3: p = 0.009, pH 7: p = 0.038). Considerable differences of mean values were found for Post-Swallow Maximum and Period of Sphincter Activity. Also, Pre-Swallow Maximum values were found to be highest with the strongest acid. Relaxation Times showed a slight trend of prolongation for the highest bolus acidity. Prolonged Restitution Times may represent a reflexive protective mechanism triggered by receptors in the pharyngeal mucosa or the UES preventing regurgitation of acid into the pharynx and larynx, besides representing ongoing attempts of acid clearance. Exposure to high levels of acidity by a swallowed bolus does influence UES functions during swallowing.

Three-dimensional analysis of the velopharyngeal region in patients with cleft palate and healthy individuals.

PURPOSE: This study aims to attain metric data of the velopharyngeal dimensions of healthy subjects as well as patients with velopharyngeal insufficiency using the example of cleft and lip palate (CLP) in order to determine possible differences in the volumes of both groups. METHODS: Volumes and distances of velopharyngeal areas were analyzed retrospectively using cone beam computed tomography data sets (n = 60). Group 1 included healthy patients receiving dental implants (n = 31). Group 2 was represented by patients with surgically closed cleft lip and palate (n = 29). RESULTS: Biggest differences among mean values of both groups were found for: minimum axial area (p = 0.000), airway area caudal (p = 0.000), distance between posterior nasal spine and posterior pharyngeal wall (PPW) (p = 0.014), mean distance between velum and PPW (p = 0.000), length of PPW (p = 0.000) and length of anterior pharyngeal wall (p = 0.000). CONCLUSION: Differences in the shape and geometry of the velopharyngeal area in subjects with a regular velopharyngeal structure and function and patients with cleft palate do exist. The significant differences found here can be categorized into two groups: one reflects distances between the anterior and posterior pharynx, presenting longer distances for patients with CLP. The second significant difference regards values of length in cranio-caudal direction, which is longer in healthy subjects. With regards to these values, one could conclude, that even though total volumes of both groups did not differ in size, group 1 shows three-dimensional velopharyngeal shapes that are longer and narrower, whereas shapes of patients of group 2 tend to be wider and shorter in general.

Deglutition in Patients With Hypernasality Associated With Unilateral Cleft Lip and Palate Evaluated With High-Resolution Manometry.

OBJECTIVE: To evaluate pharyngeal pressure profiles during swallowing in patients with unilateral cleft lip and palate (UCLP) and identify compensation mechanisms. DESIGN: Prospective experimental study. SETTING: University Hospital and Medical School. PARTICIPANTS: Ten volunteers and 10 patients with nonsyndromic repaired UCLP with hypernasality (age: 19-27 years, 5 females and 5 males per group) were included. INTERVENTIONS: All participants swallowed 2 and 10 mL of water and underwent high-resolution manometry (HRM). MAIN OUTCOME MEASURES: Pharyngeal and upper esophageal sphincter (UES) parameters were measured using HRM. Student t test was used for statistical intergroup comparisons. Additionally, the Sydney Swallowing Questionnaire (SSQ) was used as a subjective measure. RESULTS: Patients exhibited reduced velopharyngeal closing pressure and velopharyngeal and tongue base (TB) region contraction times, compared to volunteers (P < .05). The UES opening and closing functions did not change. The SSQ revealed nasal regurgitation in some patients. CONCLUSIONS: In patients with UCLP, velopharyngeal region alterations are caused by impaired muscle force and function. The reduced TB contraction time may be a compensation mechanism allowing bolus transportation without nasal regurgitation. However, deglutition is not completely altered since UES function remains normal. Future studies will need to reveal at which point a decrease in velopharyngeal closing pressure will result in velopharyngeal insufficiency.

Euclidean distances of laryngopharyngeal structures obtained from CT data for preclinical development of laryngoscopic devices.

PURPOSE: This study aims to determine Euclidean distances between landmark structures in the larynx and pharynx to optimize endoscope shaft designs with regard to gentle and patient-oriented handling. METHODS: Four Euclidean distances between landmarks in the larynx and pharynx were analyzed based on CT data of 66 patients. Distance (1): labium inferius oris-posterior pharyngeal wall at the cervical vertebra C1 (atlas), anterior edge of the tuberculum anterius atlantis. Distance (2): posterior pharyngeal wall adjacent to C1-entrance of pyriform sinus. Distance (3): inferior edge of the uvula-superior edge of the epiglottis. Distance (4): base of the vallecula-posterior pharyngeal wall. The minimum angular field of view α required to observe the glottis with a rigid transoral laryngoscope was derived trigonometrically from distances (2) and (4). RESULTS: Average Euclidean distances measured: Distance (1): 90.7 mm ± 6.9 mm in men and 86.9 mm ± 5.9 mm in women. (2): 73.7 mm ± 13.4 mm and 56.2 mm ± 7.6 mm. (3): 25.2 mm ± 8.6 mm and 18.5 mm ± 6.8 mm. (4): 20.8 mm ± 4.6 mm and 16.5 mm ± 3.4 mm. α: 16.0° ± 3.9° and 16.6 ± 4.3°. CONCLUSIONS: As expected, statistically significant sex-related differences could be observed for distances (1)-(4). The results indicate that the length of transoral laryngoscopes should not be below 110 mm and that a minimum angular field of view of α = 17° is required to fully observe the laryngeal inlet.

[Evaluation of velopharyngeal closing pressure during trumpet play with high-resolution manometry]. / Hochauflösungsmanometrische Evaluation des velopharyngealen Verschlussdrucks beim Trompetenspiel.

OBJECTIVE: In about one-third of brass instrumentalists, there are stress-related insufficiencies of velopharyngeal closure (VPC), i. e. the intraoral pressure exceeds the barrier formed by the VPC. Here, it was the aim to measure the VPC closing pressure while playing a trumpet and to evaluate the influence of a 30 minute stress sequence on the muscular activities in the VPC. MATERIAL AND METHODS: Sample: 6 healthy volunteers; task: to play the sound h1 for 5 seconds with 85 dB(A) and with 100 dB(A). METHODOLOGY: High-resolution manometry (HRM). SAMPLING: t0: measurement without warm up phase t1 after 30 min trumpet play; practice phase with predefined pieces of music. VARIABLES: mean (pmit), minimum (pmin) and maximum pressure (pmax) in the VPA at t0 and t1. STATISTICS: testing for normal distribution, t-test. RESULTS: All measured pressures in the VPC decreased from t0 to t1 for tones produced at 85 dB(A). For 100 dB(A) tones only the pmin decreased significantly. The pressures in the VPA were higher at 100 dB(A) tones overall compared to 85 dB(A) tones, significant differences were found for pmin and pmax at t0. CONCLUSION: Tones played at louder volumes require a stronger muscular contraction in the VPC. The lower VPC pressure after the exercise phase (t1) can either result from a physiological muscular adaptation to the pressure level necessary for a sufficient VPC or already be a sign of muscular fatigue. These findings may be important to assess the work ability of wind instrumentalists by HRM. As shown for the phonation, the VPC pressure profile for the trumpet play can also be described with a three-phase model consisting of an initiation, a stable phase and a termination.

Swallowing Function After Continuous Neuromuscular Electrical Stimulation of the Submandibular Region Evaluated by High-Resolution Manometry.

Although neuromuscular electrical stimulation (NMES) is increasingly used in dysphagia therapy, patient responses to NMES are inconsistent and conflicting results have been reported. This, together with a lack of information about the effects of NEMS on the swallowing process, has led to an ongoing debate about its impact on swallowing function. In order to address this, we set out to (i) collect baseline information on the physiological effects of NMES on the complex pharyngeal phase of swallowing and (ii) to compare two different stimulation protocols. In doing so, we provide information useful for evaluating the therapeutic effectiveness of NMES on the swallowing process. In a prospective study, 29 healthy participants performed water swallows after receiving continuous NMES for 10 min. The stimulus was applied in the submandibular region using one of two different stimulation protocols: low-frequency stimulation (LFS) and mid-frequency stimulation (MFS). Swallowing parameters of the pharynx and UES were measured using high-resolution manometry. Maximum tongue base pressure increased by 8.4% following stimulation with the MFS protocol. Changes in UES function were not found. LFS stimulation did not result in any significant changes in the parameters examined. The MFS protocol enhances tongue base retraction during swallowing in healthy volunteers. The magnitude of the effect, however, was small, possibly due to the ability of healthy subjects to compensate for external influences, such as NMES, and may actually prove to be much greater in patients with diminished tongue base retraction. Thus, further studies are needed to determine whether a similar effect is also achievable in dysphagic patients with impaired bolus propulsion, possibly allowing MFS stimulation of the tongue base region to be used as an additional treatment tool.

CD24+ tumor-initiating cells from oral squamous cell carcinoma induce initial angiogenesis in vivo.

BACKGROUND: In oral squamous cell carcinoma (OSCC), a minor subset of cancer stem cells has been identified using the surface marker CD24. The CD24+ cell population is involved in initiating, maintaining, and expanding tumor growth, but has not been reported to be involved in angiogenesis to date. METHODS: NOD/SCID mice were equipped with dorsal skinfold chambers and gelatin sponges seeded with CD24+, CD24-, and unsorted cancer cells suspended in Matrigel® were implanted. Following intravital fluorescence microscopy, specimens were examined by immunohistology. RESULTS: Sponges seeded with CD24+ cells showed a significantly higher functional capillary density than those seeded with CD24- cells. The presence of endothelial cells was confirmed by immunohistochemistry for CD31. CONCLUSION: For the first time, CD24+ tumorigenic cells with angiogenic potential, which were isolated from OSCC, were characterized. Our findings provide a promising in vivo model to facilitate the development of therapeutic agents against cancer stem cells and their angiogenic pathways.

[Effect of Bolus Volume on Pharyngeal Swallowing Dynamics Evaluated with Small High-Resolution Manometry Catheters]. / Einfluss des Schluckvolumens auf die Pharynxdynamik, evaluiert mit dünnen Hochauflösungsmanometriesonden.

The bolus volume has a modulating effect on the swallowing dynamics, but previously reported adaptations of the pharyngeal function have been inconsistent. Therefore, the aim of this study was to comprehensively evaluate changes of pressure and time parameters in the pharynx and upper esophageal sphincter (UES) in relation to the swallowed bolus volume with high-resolution manometry (HRM). To examine the normal swallowing physiology, particularly thin HRM probes were used, which were expected to influence the investigated structures only minimally.10 healthy volunteers accomplished 10 swallows with 2 and 10 ml water respectively in an upright position, while an HRM-examination was performed. Pressure and time parameters of the velopharynx, the tongue base region and the UES were determined and analyzed for statistical differences with respect to the bolus volume.Swallowing larger bolus volumes resulted in both, a longer closure of the velopharynx and in a longer opening of the UES. Volume dependent pressure changes in the pharyngeal swallowing sequence were not detectable.Under the chosen test conditions, bolus volume had an impact on the time parameters of the pharyngeal phase, thus, temporal adaptations of the automated swallowing dynamics were detected. Changes in pharyngeal pressure parameters as shown in other studies cannot be confirmed. They may be due to HRM probes with a larger diameter, which take an effect on the pharyngeal structures themselves. With regard to diagnostic aspects, HRM studies should always be conducted with different bolus volumes in order to investigate the swallowing process completely.

Calculation of upper esophageal sphincter restitution time from high resolution manometry data using machine learning.

OBJECTIVE: After swallowing, the upper esophageal sphincter (UES) needs a certain amount of time to return from maximum pressure to the resting condition. Disturbances of sphincter function not only during the swallowing process but also in this phase of pressure restitution may lead to globus sensation or dysphagia. Since UES pressures do not decrease in a linear or asymptotic manner, it is difficult to determine the exact time when the resting pressure is reached, even when using high resolution manometry (HRM). To overcome this problem a Machine Learning model was established to objectively determine the UES restitution time (RT) and moreover to collect physiological data on sphincter function after swallowing. METHODS AND MATERIAL: HRM-data of 15 healthy participants performing 10 swallows each were included. After manual annotation of the RT interval by two swallowing experts, data were transferred to the Machine Learning model, which applied a sequence labeling modeling approach based on logistic regression to learn and objectivize the characteristics of all swallows. Individually computed RT values were then compared with the annotated values. RESULTS: Estimates of the RT were generated by the Machine Learning model for all 150 swallows. When annotated by swallowing experts mean RT of 11.16s±5.7 (SD) and 10.04s±5.74 were determined respectively, compared to model-generated values from 8.91s±3.71 to 10.87s±4.68 depending on model selection. The correlation score for the annotated RT of both examiners was 0.76 and 0.63 to 0.68 for comparison of model predicted values. CONCLUSIONS: Restitution time represents an important physiologic swallowing parameter not previously considered in HRM-studies of the UES, especially since disturbances of UES restitution may increase the risk of aspiration. The data presented here show that it takes approximately 9 to 11s for the UES to come to rest after swallowing. Based on maximal RT values, we demonstrate that an interval of 25-30s in between swallows is necessary until the next swallow is initiated. This should be considered in any further HRM-studies designed to evaluate the characteristics of individual swallows. The calculation model enables a quick and reproducible determination of the time it takes for the UES to come to rest after swallowing (RT). The results of the calculation are partially independent of the input of the investigator. Adding more swallows and integrating additional parameters will improve the Machine Leaning model in the future. By applying similar models to other swallowing parameters of the pharynx and UES, such as the relaxation time of the UES or the activity time during swallowing, a complete automatic evaluation of HRM-data of a swallow should be possible.

Effect of saline inhalation on vocal fold epithelial morphology evaluated by optical coherence tomography.

OBJECTIVES/HYPOTHESIS: Examination of tissue structures by optical coherence tomography (OCT) has been shown to be useful on mucous membranes of the vocal folds, but so far its application to the human larynx has been limited because it is technically cumbersome and usually needs to be performed with sedation. Here a newly developed, noninvasive combined laryngoscopy and OCT procedure is described and its suitability for ambulatory OCT studies evaluated. Because inhalation therapies utilizing saline solutions are commonly used as a treatment option for disorders of the airways, and vocal fold epithelium is most likely to be affected due to its superficial positioning, epithelial thickness was chosen as a relevant test parameter and evaluated before and after saline inhalation. METHODS: Seven vocally healthy participants performed a 10-minute inhalation of saline solution and underwent a combined laryngoscopy and OCT before and after the inhalation therapy. Endoscopy was performed using a newly developed combined laryngoscopy and OCT device. The OCT images were used to estimate the epithelial thickness of the vocal folds. RESULTS: Epithelial thickness measured in all participants before treatment was comparable in size reported in previous studies. Statistical differences before and after inhalation were not detected. CONCLUSION: The newly developed combined laryngoscopy and OCT procedure enables rapid investigation of the vocal fold epithelium. Inhalation of saline solution did not appear to affect the thickness of the epithelium of the vocal folds in vocally healthy subjects, as evaluated by OCT. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:E332-E336, 2016.

Automated working distance adjustment enables optical coherence tomography of the human larynx in awake patients.

Optical coherence tomography (OCT) provides structural information of laryngeal tissue which is comparable to histopathological analysis of biopsies taken under general anesthesia. In awake patients, movements impede clinically useful OCT acquisition. Therefore, an automatic compensation of movements was implemented into a swept source OCT-laryngoscope. Video and OCT beam path were combined in one tube of 10-mm diameter. Segmented OCT images served as distance sensor and a feedback control adjusted the working distance between 33 and 70 mm by synchronously translating the reference mirror and focusing lens. With this motion compensation, the tissue was properly visible in up to 88% of the acquisition time. During quiet respiration, OCT contrasted epithelium and lamina propria. Mean epithelial thickness was measured to be 109 and [Formula: see text] in female and male, respectively. Furthermore, OCT of mucosal wave movements during phonation enabled estimation of the oscillation frequency and amplitude. Regarding clinical issues, the OCT-laryngoscope with automated working distance adjustment may support the estimation of the depth extent of epithelial lesions and contribute to establish an indication for a biopsy. Moreover, OCT of the vibrating vocal folds provides functional information, possibly giving further insight into mucosal behavior during the vibratory cycle.

Impact of neuromuscular electrical stimulation on upper esophageal sphincter dynamics: a high-resolution manometry study.

OBJECTIVES: Beside traditional dysphagia therapy, neuromuscular electrical stimulation (NMES) has been proposed to treat patients with dysphagia. Considering the complexity of the nerve-muscle interaction during swallowing, the underlying physiology of NMES remains unclear. Here, we addressed the question of whether NMES can modify upper esophageal sphincter (UES) dynamics. METHODS: In a prospective study, 26 healthy volunteers performed water swallows with and without NMES. The stimulus was applied in a participant- and operator-initiated stimulation above, near, and below the motor threshold. Swallowing parameters were measured using high-resolution manometry. RESULTS: The UES relaxation time was found to be extended by 10%, indicating a modification in UES dynamics. CONCLUSIONS: The chosen NMES paradigm influenced the involuntary swallowing phase by extending relaxation time, providing more time for bolus passage into the esophagus. Future studies will have to evaluate if this effect can be found in patients with dysphagia and whether it is beneficial for treatment.