Michael Jungheim

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

Abstract. 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 135  μm 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.

Electrical Stimulation in Treatment of Pharyngolaryngeal Dysfunctions

Objective: Neuromuscular electrical stimulation (NMES) has been proposed in the treatment of laryngopharyngeal dysfunctions (dysphonia, dyspnoea, dysphagia) for more than 40 years. Several studies have investigated possible therapeutic effects. Some researchers described favourable results, whereas others did not find relevant benefits. This article aims to review available studies to give an overview regarding the current state of knowledge. Methods: We conducted a selective literature search using PubMed. Results: In total, 356 papers were identified: 6 case reports, 11 reviews, 43 prospective clinical trials and 3 retrospective trials were found. Conclusion: Due to different stimulation protocols, electrode positioning and various underlying pathological conditions, summarizing the present studies appears to be difficult. However, there is evidence that NMES is a valuable adjunct in patients with dysphagia and in patients with vocal fold paresis. Nevertheless, more empirical data is needed to fully understand the benefits provided by NMES. Further research suggestions are put forward.

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.

A boy with mild mental retardation, mild sensorineural hearing loss and mild facial dysmorphism caused by a 19p13.2 deletion: A case report and review of the literature

The investigation of patients with congenital anomalies and/or intellectual disability with modern genetic methods allows the recognition of an increasing number of cases with these chromosomal rearrangements. Here, we present a mildly mentally retarded boy with mild facial dysmorphism, language development delay, mild sensorineural hearing loss due to a deletion of 1,14 Mb on chromosome 19p 13.2. The deletion was de novo and familial history negative for this disorder. To our knowledge this is the first description of a patient with symptoms mentioned above associated with a 19p13.2-p13.2 deletion.

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

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.

Event Prediction in Pharyngeal High-Resolution Manometry

A prolonged phase of increased pressure in the upper esophageal sphincter (UES) after swallowing might result in globus sensation. Therefore, it is important to evaluate restitution times of the UES in order to distinguish physiologic from impaired swallow associated activities. Estimating the event \(t^{\star }\) where the UES has returned to its resting pressure after swallowing can be accomplished by predicting if swallowing activities are present or not. While the problem, whether a certain swallow is pathologic or not, is approached in Mielens (J Speech Lang Hear Res 55:892–902, 2012), the analysis conducted in this paper advances the understanding of normal pharyngoesophageal activities.

Towards Fully Automated Determination of Laryngeal Adductor Reflex Latencies through High-Speed Laryngoscopy Image Processing

Protective reflexes of the larynx help to avoid intrusion of foreign particles into the lower airways, which can lead to aspiration pneumonia. These protective mechanisms include the Laryngeal Adductor Reflex (LAR), a rapid adduction of the vocal folds. Up to now, the LAR latency could only be determined manually by visually assessing laryngoscopic high-speed video sequences obtained during and after stimulation of the larynx by water droplet impact. Here, we present a novel image processing algorithm based on difference image calculation and optical flow analysis for a more objective LAR latency determination. To evaluate our prototype algorithm, we compared the results obtained for a set of example sequences with the values given by two expert phoniatricians. The results show a very good LAR stimulation detection performance. LAR onset detection remains challenging for our algorithmic approach as well as for the human perceptive system, as demonstrated by a low inter-rater reliability.

Towards microprocessor-based control of droplet parameters for endoscopic laryngeal adductor reflex triggering

Abstract The so-called Laryngeal Adductor Reflex (LAR) protects the respiratory tract from particle intrusion by quickly approximating the vocal folds to close the free glottal space. An impaired LAR may be associated with an increased risk of aspiration and other adverse conditions. To evaluate the integrity of the LAR, we recently developed an endoscopic prototype for LAR triggering by shooting accelerated droplets onto a predefined laryngeal target region. We now modified the existing droplet-dispensing system to adapt the fluid system pressure as well as the valve opening time to user-chosen values autonomously. This has been accomplished using a microcontroller board connected to a pressure sensor and a mechatronic syringe pump. For performance validation, we designed a measurement setup capable of tracking the droplet along a vertical trajectory. In addition to the experimental setup, the influence of parameters such as system pressure and valve opening time on the micro-droplet formation is presented. Further development will enable the physician to adjust the droplet momentum by setting a single input value on the microcontroller-based setup, thus further increasing usability of the diagnostic device.