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Summary The ability to provide absolute calibrated measurement of the laryngeal structures during phonation is of paramount importance to voice science and clinical practice. Calibrated three-dimensional measurement could provide essential information for modeling purposes, for studying the developmental aspects of vocal fold vibration, for refining functional voice assessment and treatment outcomes evaluation, and for more accurate staging and grading of laryngeal disease. Recently, a laser-calibrated transnasal fiberoptic endoscope compatible with high-speed videoendoscopy (HSV) and capable of providing three-dimensional measurements was developed. The optical principle employed is to project a grid of 7 × 7 green laser points across the field of view (FOV) at an angle relative to the imaging axis, such that (after calibration) the position of each laser point within the FOV encodes the vertical distance from the tip of the endoscope to the laryngeal tissues. The purpose of this study was to develop a precise method for vertical calibration of the endoscope. Investigating the position of the laser points showed that, besides the vertical distance, they also depend on the parameters of the lens coupler, including the FOV position within the image frame and the rotation angle of the endoscope. The presented automatic calibration method was developed to compensate for the effect of these parameters. Statistical image processing and pattern recognition were used to detect the FOV, the center of FOV, and the fiducial marker. This step normalizes the HSV frames to a standard coordinate system and removes the dependence of the laser-point positions on the parameters of the lens coupler. Then, using a statistical learning technique, a calibration protocol was developed to model the trajectories of all laser points as the working distance was varied. Finally, a set of experiments was conducted to measure the accuracy and reliability of every step of the procedure. The system was able to measure absolute vertical distance with mean percent error in the range of 1.7% to 4.7%, depending on the working distance.

The purpose of this paper is to report on the first in vivo application of a recently developed transoral, dual-sensor pressure probe that directly measures intraglottal, subglottal, and vocal fold collision pressures during phonation. Synchronous measurement of intraglottal and subglottal pressures was accomplished using two miniature pressure sensors mounted on the end of the probe and inserted transorally in a 78-year-old male who had previously undergone surgical removal of his right vocal fold for treatment of laryngeal cancer. The endoscopist used one hand to position the custom probe against the surgically medialized scar band that replaced the right vocal fold and used the other hand to position a transoral endoscope to record laryngeal high-speed videoendoscopy of the vibrating left vocal fold contacting the pressure probe. Visualization of the larynx during sustained phonation allowed the endoscopist to place the dual-sensor pressure probe such that the proximal sensor was positioned intraglottally and the distal sensor subglottally. The proximal pressure sensor was verified to be in the strike zone of vocal fold collision during phonation when the intraglottal pressure signal exhibited three characteristics: an impulsive peak at the start of the closed phase, a rounded peak during the open phase, and a minimum value around zero immediately preceding the impulsive peak of the subsequent phonatory cycle. Numerical voice production modeling was applied to validate model-based predictions of vocal fold collision pressure using kinematic vocal fold measures. The results successfully demonstrated feasibility of in vivo measurement of vocal fold collision pressure in an individual with a hemilaryngectomy, motivating ongoing data collection that is designed to aid in the development of vocal dose measures that incorporate vocal fold impact collision and stresses.

OBJECTIVES/HYPOTHESIS We previously developed an instrument called the Aerodynamic Vocal Fold Driver (AVFD) for intraoperative magnified assessment of vocal fold (VF) vibration during microlaryngoscopy under general anesthesia. Excised larynx testing showed that the AVFD could provide useful information about the vibratory characteristics of each VF independently. The present investigation expands those findings by testing new iterations of the AVFD during microlaryngoscopy in the canine model. STUDY DESIGN Animal model. METHODS The AVFD is a handheld instrument that is positioned to contact the phonatory mucosa of either VF during microlaryngoscopy. Airflow delivered through the AVFD shaft to the subglottis drives the VF into phonation-like vibration, which enables magnified observation of mucosal-wave function with stroboscopy or high-speed video. AVFD-driven phonation was tested intraoperatively (n = 26 VFs) using either the original instrument design or smaller and larger versions three-dimensionally printed from a medical grade polymer. A high-fidelity pressure sensor embedded within the AVFD measured VF contact pressure. Characteristics of individual VF phonation were compared with typical two-fold phonation and compared for VFs scarred by electrocautery (n = 4) versus controls (n = 22). RESULTS Phonation was successful in all 26 VFs, even when scar prevented conventional bilateral phonation. The 15-mm-wide AVFD fits best within the anteroposterior dimension of the musculo-membranous VF, and VF contact pressure correlated with acoustic output, driving pressures, and visible modes of vibration. CONCLUSIONS The AVFD can reveal magnified vibratory characteristics of individual VFs during microlaryngoscopy (e.g., without needing patient participation), potentially providing information that is not apparent or available during conventional awake phonation, which might facilitate phonosurgical decision making. LEVEL OF EVIDENCE NA Laryngoscope, 130: 1980-1988, 2020.

OBJECTIVES/HYPOTHESIS Photoangiolytic precision afforded by the 532-nm potassium-titanyl-phosphate (KTP) laser relies on predictable energy delivery. Inadequate energy output can cause vessel rupture, and excessive energy can cause thermal damage. The quality of the cleaved surface and carbon deposits from ablated tissue are two factors that could negatively impact fiber performance. The effects of these on energy output and blood vessel coagulation were assessed using a chorioallantoic membrane (CAM) model. STUDY DESIGN Comparative analysis. METHODS Laser fibers with carbon debris, optimal fiber cleaving, and suboptimal cleaving were inspected at three times magnification, and the light dispersion pattern of each fiber was rated. The average energy output from consecutive pulses through each fiber configuration was recorded. The effect of these fiber conditions on clinical efficacy was estimated by measuring vessel coagulation versus rupture in the CAM model. Repeated measures analysis of variance compared results. RESULTS Carbon debris and suboptimal cleaving resulted in decreased energy output in comparison to optimal cleaving ([-Δ244 mJ, d = 4.31, P

Objectives: Gels composed of carboxymethylcellulose (CMC) and cross-linked hyaluronic acid are commonly used as temporary or resorbable injectable materials for vocal fold medialization. However, there is limited information about tissue injection patterns, soft tissue reaction, degradation, and residence time, particularly for the newer CMC gels. Study Design: Prospective, laboratory. Methods: Ten canines underwent paraglottic (deep to the vocal ligament) microlaryngoscopic injection with about 100 µL (0.1 mL) of cross-linked hyaluronic acid (Restylane) in the right vocal fold and about 100 µl (0.1 mL) of CMC gel in the left vocal fold. Two commercial CMC gels of similar formulation (Prolaryn Gel and Renú Gel) were used in 5 animals each. Two subjects were sacrificed for histologic analysis at 3, 13, 29, 42, and 55 days. Results: Histology showed that injected Restylane formed cohesive ovoid-shaped aggregated implants with minimal dispersion, inflammation, or cellular invasion in all subjects. Approximately 86% of Restylane injected remained at 8 weeks, as estimated from postmortem, high-resolution magnetic resonance imaging scans. In contrast, histology showed that both CMC gels dispersed widely through fascial planes during and after injection within and outside the thyroarytenoid muscle fascicles. There was a robust macrophage and histiocyte phagocytic response, with moderate to severe inflammation noted around residual CMC gel at early time points, and at 6 to 8 weeks, very little free gel was observed. Conclusions: None of the studied materials induced a clinical inflammatory reaction on laryngoscopy such that they would be considered problematic or dangerous. Restylane demonstrated superior injection localization, tissue compatibility, and residence time. Both CMC gels did not localize well in the paraglottic region, and there was a robust inflammatory response, with clearance by macrophages and short residence time. These results suggest that CMC gels may have a more limited application than previously thought for vocal fold medialization in patients in whom the injection is being used to achieve voice enhancement while awaiting reinnervation. Level of Evidence: NA

Objective: The goal of this work was to create implantable stimulator systems that could be used in animal experiments on laryngeal paralysis, including “closed-loop” stimulation of impaired muscles triggered by electromyographic (EMG) potentials from healthy muscles. Study Design: Iterative device design and testing. Methods: A series of microcontroller-based implantable devices were built that incorporated increasingly sophisticated features for stimulation, EMG recording, and communication across the skin. Specific engineering challenges included minimizing power consumption, achieving charge-balanced and relatively high stimulation capacity, implementing noninvasive communication across the skin, providing real-time processing of EMG signals, and mitigating effects of shock artifacts. Bench testing was used to verify performance. Results: Two prototypes are described in detail. Each system is based on an “implant” and an external “communication adapter” that interfaces both with the implant and with external computers for adjustments and monitoring. The first version described is inductively powered and referred to as the “inductive laryngeal stimulator.” It uses inductive coupling for both power and communication and performs EMG processing in the communication adapter module. The second version, a “battery-powered laryngeal stimulator,” consists of an autonomous battery-powered implant with onboard EMG processing and artifact control; it communicates by infrared light with the external communication adapter for setup and monitoring. Conclusions: The devices met design and performance specifications and have proved useful in the animal experiments that are described in Part 2 of this series. Detailed descriptions of the circuits and their firmware are made available in the Appendix. Level of Evidence: NA

OBJECTIVES/HYPOTHESIS Lubricin/proteoglycan-4 (PRG4) lubricates connective tissues such as joints and tendon sheaths, enabling them to better withstand shearing and frictional forces during motion. We wondered whether PRG4 might play a role in phonation, as normal vocal folds withstand repetitive, high-velocity deformations remarkably well. As a first step, we tested whether PRG4 is expressed in vocal folds. STUDY DESIGN Laboratory study. METHODS Anatomical and molecular methods were applied to 47 larynges from humans, macaque (Macaca fascicularis), canines, pigs, calves, and rats. Immunohistochemistry (IHC), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) methods were used to test for the presence of PRG4. RESULTS In all species, the true vocal fold lamina propria (TVF-LP) was positive for PRG4 by IHC, whereas immunoreactivity of the false vocal fold was weak or absent, depending on the species. Human TVF-LP was strongly stained across all layers. Immunoreactivity was seen variably on the vocal fold surface and within the vocal fold epithelium, in the conus elasticus and thyroglottic ligament, and at the tip of vocal process. Western blots of four humans and six pigs demonstrated immunoreactivity at appropriate molecular weight. qRT-PCR of pig tissues confirmed PRG4 mRNA expression, which was highest in the TVF-LP. CONCLUSIONS PRG4 was found in phonatory tissues of six mammals. We suggest it might act as a lubricant within the lamina propria and possibly on the vocal fold surface, limiting phonation-related damage to vocal fold extracellular matrix and epithelium, and enhancing vocal efficiency by reducing internal friction (viscosity) within the vocal fold. LEVEL OF EVIDENCE NA Laryngoscope, 129:E229-E237, 2019.

Tracking recovery after nerve injury may require many intermittent assessments over long periods, preferably with non- or minimally invasive methods. We developed subcutaneous electrical connection ports (ECPs) for repeated connection to nerve cuff or intramuscular electrodes via transdermal needles and evaluated them during studies of laryngeal reinnervation.Animal experiment.Laboratory.ECPs were designed and 3-dimensionally printed for connection to bipolar electrodes with biocompatible polymers. Dual compartments filled with conductive silicone capped with nonconductive silicone were used to make the connections between electrode leads and transdermally inserted needles. Ten dogs (19-29 kg) were implanted with 22 ECPs. In 7 dogs, 11 electrodes were placed on recurrent laryngeal nerves proximal to transection and suture repair to track laryngeal reinnervation. In 6 dogs, 8 spinal accessory nerve cuff electrodes were used to stimulate neck muscle contraction. In 2 dogs, 3 electrodes were implanted in the thyroarytenoid muscle. Stimulation thresholds, electromyography, and videolaryngoscopic imaging were obtained in 156 tests over survival periods up to 32 months. Stimulation data provided information about ECP performance.ECPs added negligible resistance to electrodes (mean ± SD, 2.14 ± 0.9 Ω). Despite some electrode leads breaking distally, ECPs were reliable and well tolerated at implant sites and enabled periodic assessment of nerve and muscle function over the time course of laryngeal reinnervation. Histology showed ECP encapsulation as thin layers of connective tissue and minimal acute inflammation.Custom ECPs are easily fabricated and cause little tissue reaction over months to years of subcutaneous implantation, facilitating long-term physiologic studies.

To compare the physical characteristics of 3 laser-protected endotracheal tubes (LPETs) commonly used in endoscopic laser surgery. To report potential intraoperative problems related to LPET use and suggest practical solutions.Comparative analysis.Academic laboratory.Physical characteristics of the Mallinckrodt Laser-Flex (MTL), Medtronic Laser-Shield II (ML-II), and Rusch LaserTubus (RL) were compared. The effect of bending LPETs on airflow resistance was estimated with a pressure transducer. The force required to pull each tube through the glottis and the pressure exerted during this maneuver were measured in a fresh cadaveric human larynx.The design features and physical characteristics of LPETs differ, including varying balloon-tip lengths. Bending LPETs to acute angles caused significant pressure increase within the RL tube (Δ 3.42 cm HThe ML-II tube had the most favorable characteristics, with minimal pressure during extubation and resistance to kinking. The RL tube kinks readily with a resultant increase in resistance to airflow. The MTL tube extends farther into the trachea due to a relatively elongated balloon-tip configuration. Future LPET designs should incorporate features that avoid intraoperative difficulties related to airway protection and ventilation.

Excessive vocal fold collision pressures during phonation are considered to play a primary role in the formation of benign vocal fold lesions, such as nodules. The ability to accurately and reliably acquire intraglottal pressure has the potential to provide unique insights into the pathophysiology of phonotrauma. Difficulties arise, however, in directly measuring vocal fold contact pressures due to physical intrusion from the sensor that may disrupt the contact mechanics, as well as difficulty in determining probe/sensor position relative to the contact location. These issues are quantified and addressed through the implementation of a novel approach for identifying the timing and location of vocal fold contact, and measuring intraglottal and vocal fold contact pressures via a pressure probe embedded in the wall of a hemi-laryngeal flow facility. The accuracy and sensitivity of the pressure measurements are validated against ground truth values. Application to in vivo approaches are assessed by acquiring intraglottal and VF contact pressures using a synthetic, self-oscillating vocal fold model in a hemi-laryngeal configuration, where the sensitivity of the measured intraglottal and vocal fold contact pressure relative to the sensor position is explored.

Introduction: Endotracheal (ET) intubation is a common cause of acquired glottic stenosis. Severe cases often require an irreversible arytenoidectomy/cordectomy, which typically results in poor voice quality. Adult human cadaver larynges were studied to gain insights about ET tube–induced posterior glottic injuries, hoping to create a less invasive remedy. Study Design: Human cadaver investigation and case reports. Methods: Microlaryngeal assessments were done on 10 human cadaver larynges (5 men, 5 women) with and without ET tubes. After supracricoid soft tissue resection, measurements were obtained, including the distance between the outer diameter of the ET tube and the medial aspect of the cricoarytenoid joint facet. Additionally, measurements of the circumferential arc of differently sized ET tubes were made alongside both cricoarytenoid joint capsules. This information was used to design a silastic stent that would function as a self-retaining interarytenoid spring to treat posterior glottic stenosis in 5 patients. Four of 5 patients included in the clinical study were tracheotomy dependent, primarily because of glottic stenosis. The human surgical technique is described in detail. Results: The shortest distance between the outer diameter of the ET tube to the medial cricoid facet averaged 5.02 mm in men and 3.62 mm in women. On the basis of the diameter of the intralaryngeal component of the initially round stent, and the position of the cricoarytenoid joint facets, the interarytenoid spring would have a subtended arc between 110° and 175°. These data helped fashion parameters for modifying a conventional T-tube to form a new self-retaining silastic interarytenoid spring. The first 5 human cases have been successful, allowing effective tracheotomy tube decannulation and excellent voice quality. Conclusions: The anatomic investigation herein provided key insights into ET tube–induced glottic stenosis and facilitated a new straightforward procedure to surgically improve the airway yet preserve excellent vocal function in patients with acquired glottic stenosis. Level of Evidence: NA

We demonstrate optical biopsy of vocal folds to assess its surface and subsurface movement during phonation on ex-vivo calf larynx using parallel OCT (POCT). In this technique, we will enable simultaneous interrogation of multiple locations along the vocal fold, there by eliminating motion-blur artifacts exhibited by the sequential sampling provided by conventional flying-spot OCT. Currently, in voice clinics, laryngologists and speech-language pathologists rely heavily on Video Stroboscopy (VS) coupling with, visual judgments of vocal fold morphology and auditory perceptions of voice quality, to make effective diagnostic, surgical and therapeutic decisions. There is a constant need of an endoscopic imaging tool in voice clinics that can directly capture the three-dimensional (3D) surface motion of the vocal folds in real time as patients phonate. To address the need, we will present a POCT/VS imager that will combine parallel swept source OCT technique with VS to provide a real time display of the vocal folds in all three axial dimensions during phonation. The results will yield cross sections (B-Scans) with ~16 co-linear sampling locations spread over ~5mm on a phonating ex-vivo calf larynx showing fluid periodic cyclic motion of the vocal folds (~A-scan rate) in real time enabled by POCT approach. We will also capture VS images in sync with POCT B-scans validating the real time cross sectional probing of POCT/VS imager.

Voice disorders affect a large number of adults in the United States, and their clinical evaluation heavily relies on laryngeal videostroboscopy, which captures the medial-lateral and anterior-posterior motion of the vocal folds using stroboscopic sampling. However, videostroboscopy does not provide direct visualization of the superior-inferior movement of the vocal folds, which yields important clinical insight. In this paper, we present a novel technology that complements videostroboscopic findings by adding the ability to image the coronal plane and visualize the superior-inferior movement of the vocal folds. The technology is based on optical coherence tomography, which is combined with videostroboscopy within the same endoscopic probe to provide spatially and temporally co-registered images of the mucosal wave motion, as well as vocal folds subsurface morphology. We demonstrate the capability of the rigid endoscopic probe, in a benchtop setting, to characterize the complex movement and subsurface structure of the aerodynamically driven excised larynx models within the 50 to 200 Hz phonation range. Our preliminary results encourage future development of this technology with the goal of its use for in vivo laryngeal imaging.

Lubricin/proteoglycan-4 (PRG4) lubricates connective tissues such as joints and tendon sheaths, enabling them to better withstand shearing and frictional forces during motion. We wondered whether PRG4 might play a role in phonation, as normal vocal folds withstand repetitive, high-velocity deformations remarkably well. As a first step, we tested whether PRG4 is expressed in vocal folds.Laboratory study.Anatomical and molecular methods were applied to 47 larynges from humans, macaque (Macaca fascicularis), canines, pigs, calves, and rats. Immunohistochemistry (IHC), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) methods were used to test for the presence of PRG4.In all species, the true vocal fold lamina propria (TVF-LP) was positive for PRG4 by IHC, whereas immunoreactivity of the false vocal fold was weak or absent, depending on the species. Human TVF-LP was strongly stained across all layers. Immunoreactivity was seen variably on the vocal fold surface and within the vocal fold epithelium, in the conus elasticus and thyroglottic ligament, and at the tip of vocal process. Western blots of four humans and six pigs demonstrated immunoreactivity at appropriate molecular weight. qRT-PCR of pig tissues confirmed PRG4 mRNA expression, which was highest in the TVF-LP.PRG4 was found in phonatory tissues of six mammals. We suggest it might act as a lubricant within the lamina propria and possibly on the vocal fold surface, limiting phonation-related damage to vocal fold extracellular matrix and epithelium, and enhancing vocal efficiency by reducing internal friction (viscosity) within the vocal fold.NA Laryngoscope, 129:E229-E237, 2019.

The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen fiber direction and density in second-harmonic generation microscopy images. This paper presents a collagen tissue analysis of scarred cheek pouches of four adult male Golden Syrian hamsters as an animal model for vocal fold scarring. One cheek pouch was scarred using an electrocautery unit and the other cheek was used as a control for each hamster. A home-built upright microscope and a compact ultrafast fiber laser were used to acquire depth resolved epi-collected second-harmonic generation images of collagen fibers. To quantify the average fiber direction and fiber density in each image, we applied two-dimensional Fourier analysis and intensity thresholding at five different locations for each control and scarred tissue sample, respectively. The resultant depth-resolved average fiber direction variance for scarred hamster cheek pouches (0.61 ± 0.03) was significantly lower (p

Vocal fold kinematics and its interaction with aerodynamic characteristics play a primary role in acoustic sound production of the human voice. Investigating the temporal details of these kinematics using high-speed videoendoscopic imaging techniques has proven challenging in part due to the limitations of quantifying complex vocal fold vibratory behavior using only two spatial dimensions. Thus, we propose an optical method of reconstructing the superior vocal fold surface in three spatial dimensions using a high-speed video camera and laser projection system. Using stereo-triangulation principles, we extend the camera-laser projector method and present an efficient image processing workflow to generate the three-dimensional vocal fold surfaces during phonation captured at 4000 frames per second. Initial results are provided for airflow-driven vibration of an ex vivo vocal fold model in which at least 75% of visible laser points contributed to the reconstructed surface. The method captures the vertical motion of the vocal folds at a high accuracy to allow for the computation of three-dimensional mucosal wave features such as vibratory amplitude, velocity, and asymmetry.

Background Obesity is a major risk factor for the development of diabetes. Limb ischemia–reperfusion injury (IR) is a common clinical problem in diabetics who have compromised lower extremity perfusion. This study compared the histologic, metabolic, and functional outcomes after hind limb IR in diet-induced obese (DIO) and non-diabetic (ND) mice during the acute and the regenerative phases of IR. Methods DIO and ND mice were subjected to 1.5 h unilateral hind limb ischemia followed by 1- or 28-d IR. Muscle morphology, metabolic, and genomic stress were evaluated at days 1 and 28 IR; Acute inflammation and thrombosis were only measured at day-1 IR. At day 28, IR, skeletal muscle contractility, and maturation were also assessed. Results At day-1 IR, similar levels of acute muscle fiber necrosis were seen in both groups. DIO mice demonstrated substantially greater inflammatory, prothrombotic, and genomic stress responses, which were also associated with a greater reduction in energy substrates and Akt phosphorylation. At 28d, there was no difference in the peak forces generated in the hind limbs for the two groups. DIO mice had reduced fatigue resistance compared with ND and larger areas of fat accumulation although there was no significant difference in muscle fiber maturation. Conclusions DIO mice had an exacerbated acute response to IR with enhanced metabolic deficit, fat accumulation, and defective functional recovery during the regenerative phase of IR. These changes in fatigue resistance reflect compromised functional recovery after IR injury and have relevance for the functional recovery of patients with metabolic syndrome and insulin resistance.

Objective: This study aimed to develop and evaluate a model for teaching transcervical laryngeal injections. Methods: A 3-dimensional printer was used to create a laryngotracheal framework based on de-identified computed tomography images of a human larynx. The arytenoid cartilages and intrinsic laryngeal musculature were created in silicone from clay casts and thermoplastic molds. The thyroarytenoid (TA) muscle was created with electrically conductive silicone using metallic filaments embedded in silicone. Wires connected TA muscles to an electrical circuit incorporating a cell phone and speaker. A needle electrode completed the circuit when inserted in the TA during simulated injection, providing real-time feedback of successful needle placement by producing an audible sound. Face validation by the senior authorconfirmed appropriate tactile feedback and anatomical realism. Otolaryngologists pilot tested the model and completed presimulation and postsimulation questionnaires. Results: The high-fidelity simulation model provided tactile and audio feedback during needle placement, simulating transcervical vocal fold injections. Otolaryngology residents demonstrated higher comfort levels with transcervical thyroarytenoid injection on postsimulation questionnaires. Conclusion: This is the first study to describe a simulator for developing transcervical vocal fold injection skills. The model provides real-time tactile and auditory feedback that aids in skill acquisition. Otolaryngologists reported increased confidence with transcervical injection after using the simulator.

Ultrafast pulsed lasers can be used to achieve remarkable precision during surgical ablation. Through nonlinear interactions with tissue, ultrafast lasers can provide a largely non-thermal mechanism of ablation and a unique ability to create targeted damage within bulk tissue. These advantages have made ultrafast lasers the ideal surgical tool for various novel applications in ophthalmology. Clinical adoption of ultrafast lasers in other surgical applications remains limited in part due to the lack of a means for fiber delivery of ultrafast laser pulses as a flexible, hand-held surgical endoscope. This review provides an overview of the recent advances in bringing this unique surgical tool into the clinic. We discuss fundamental mechanisms and limitations of ultrafast laser ablation, novel techniques for overcoming these limitations, the current state of clinical applications, and conclude with our recent efforts in developing fiber-coupled probes for flexible ultrafast laser surgery and imaging.

Efficient transfer of sound by the middle ear ossicles is essential for hearing. Various pathologies can impede the transmission of sound and thereby cause conductive hearing loss. Differential diagnosis of ossicular disorders can be challenging since the ossicles are normally hidden behind the tympanic membrane (TM). Here we describe the use of a technique termed optical coherence tomography (OCT) vibrography to view the sound-induced motion of the TM and ossicles simultaneously. With this method, we were able to capture three-dimensional motion of the intact TM and ossicles of the chinchilla ear with nanometer-scale sensitivity at sound frequencies from 0.5 to 5 kHz. The vibration patterns of the TM were complex and highly frequency dependent with mean amplitudes of 70–120 nm at 100 dB sound pressure level. The TM motion was only marginally sensitive to stapes fixation and incus-stapes joint interruption; however, when additional information derived from the simultaneous measurement of ossicular motion was added, it was possible to clearly distinguish these different simulated pathologies. The technique may be applicable to clinical diagnosis in Otology and to basic research in audition and acoustics.

Objectives: Aortic homografts integrate well with laryngeal tissue when used in reconstructive surgery. It was hypothesized that a paste of aortic homograft, rich in slow-to-degrade elastin, would compare favorably in residence time and biocompatibility to predicate materials used for vocal fold injection-medialization. Methods: An injectable aorta paste (AP) was made by pulverizing aortic homografts at −196°C (cryomilling). To assess residence time and biocompatibility, 0.3 cc was injected subdermally in guinea pigs (n = 3 per 2-, 4-, 8-, 16-, 24-week time points) followed by histological analysis. To test particle size versus residence time, APs made using 80 or 200 seconds of cryomilling were compared. Implant characteristics of AP were then compared to Restylane, Radiesse Voice (Hydroxylapatite), Radiesse Voice Gel, and Cymetra in additional animals (n = 6 per 4-, 8-, 12-week time points). Results: Injected AP formed ovoid masses with minimal inflammation. Cellular infiltration was mild and increased with survival time. There was a gradual reduction of implant volume to ~40% at 24 weeks. Increased residence time for paste with larger particles (80 cryomilling seconds) was noted. Von Kossa staining showed progressive calcification of the AP. Cymetra was difficult to reconstitute reliably but formed subdermal masses similar to AP in shape, size, and reactivity and without calcification. The other predicates showed good biocompatibility but spread more widely and erratically in the tissue. Conclusion: Aortic paste is easy to create, biocompatible, degrades slowly, and forms well-defined implants in guinea pig subdermal tissue. The AP implants calcified over time, and experiments are ongoing to determine the source of calcification and how it might be controlled or exploited clinically.

Objectives/Hypothesis: Vocal fold (VF) injections of viscous materials are typically performed using hand-operated syringes or injection guns; however, these methods can be imprecise due to accumulation of pressure, effort-related tremor, and poor feedback regarding injection volume and rate. Study Design: Apparatus development with laboratory bench-top and animal model testing. Methods: A foot pedal-triggered device for dispensing viscous materials was modified by adding a linear transducer and display for monitoring dispensed volume. In bench tests, bovine VFs were injected with fluids/materials of different viscosities (saline, glycerol, hydrogel, and liposuctioned fat) through narrow-bore needles using a range of driving pressures and air pulse durations. The device was further evaluated in >50 in vivo VF injection experiments. Results: Device function was repeatable, with high correlations (typically R2 > 0.98) between the readout and direct measures of volume, even for small volumes (

Experiments on human and on animal excised specimens as well as in vivo animal preparations are so far the most realistic approaches to simulate the in vivo process of human phonation. These experiments do not have the disadvantage of limited space within the neck and enable studies of the actual organ necessary for phonation, i.e., the larynx. The studies additionally allow the analysis of flow, vocal fold dynamics, and resulting acoustics in relation to well-defined laryngeal alterations. Purpose of Review: This paper provides an overview of the applications and usefulness of excised (human/animal) specimen and in vivo animal experiments in voice research. These experiments have enabled visualization and analysis of dehydration effects, vocal fold scarring, bifurcation and chaotic vibrations, three-dimensional vibrations, aerodynamic effects, and mucosal wave propagation along the medial surface. Quantitative data will be shown to give an overview of measured laryngeal parameter values. As yet, a full understanding of all existing interactions in voice production has not been achieved, and thus, where possible, we try to indicate areas needing further study. Recent Findings: A further motivation behind this review is to highlight recent findings and technologies related to the study of vocal fold dynamics and its applications. For example, studies of interactions between vocal tract airflow and generation of acoustics have recently shown that airflow superior to the glottis is governed by not only vocal fold dynamics but also by subglottal and supraglottal structures. In addition, promising new methods to investigate kinematics and dynamics have been reported recently, including dynamic optical coherence tomography, X-ray stroboscopy and three-dimensional reconstruction with laser projection systems. Finally, we touch on the relevance of vocal fold dynamics to clinical laryngology and to clinically-oriented research.

Objectives/Hypothesis: Early glottic cancer has been involuted by treatment with the 532 nm pulsed potassium-titanyl-phosphate (KTP) laser in initial clinical studies. Selective photoangiolysis of the sublesional circulation that allows for relative sparing of surrounding tissue is the presumed mechanism. No prior controlled animal-model study has analyzed the ability of selective coagulation of lesional microvasculature coagulation with the KTP laser to involute malignant lesions. This study tests the efficacy of photoangiolysis with the KTP laser in treating squamous cell carcinoma in an established animal model. Study Design: In vivo. Methods: Malignant lesions were induced unilaterally in the cheek pouches of 21 hamsters by applying 9,10-dimethyl-1,2-benzanthrancene. The contralateral cheek pouch served as a control. Weekly lesion photodocumentation and pulsed KTP laser (30 W, 15 msec pulse width, 2 pulses/sec) treatments were done. The endpoint of each treatment was a uniform white-blanching of the lesion. Hamsters were sacrificed 1 week after the last treatment and cheek pouches were analyzed histologically. Results: Carcinoma was confirmed in 19 hamsters, and lesions that were initially 2 mm (P = .0004). Every lesion (10/10) that initially measured 5 mm resolved after completion of the treatment period. Conclusions: Pulsed KTP laser photoangiolysis can effectively involute small malignant lesions, but may be less effective at involuting larger (>2 mm) lesions.

Objectives: Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration–approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. Methods: We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. Results: High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. Conclusions: The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.

Objectives/Hypothesis: Optical coherence tomography (OCT) can provide high-resolution (! 10‐15 lm/pixel) images of vocal fold microanatomy, as demonstrated previously. We explored physiologically triggered Fourier-domain OCT for imaging vocal folds during phonation. The goal is to visualize dynamic histological cross sections and four-dimensional data sets where multiple planes are displayed in synchronized motion. If feasible, this approach could be a useful research tool and spur development of new clinical instrumentation. Study Design: A Fourier-domain, triggered OCT system was created and tested in experiments on excised calf larynges to obtain preliminary observations and characterize important factors affecting image quality. Methods: Larynges were imaged during phonation driven by warm, humidified air. A subglottal pressure signal was used to synchronize the OCT system with the phonatory cycle. Image sequences were recorded as functions of anatomical location or subglottal pressure. Implant materials were also imaged during vibration, both in isolation and after injection into a vocal fold. Results: Oscillations of epithelium and lamina propria were observed, and parameters such as shape, amplitude, and velocity of the vocal fold mucosal waves were found to be measurable. Ripples of mucosal wave as small as 100 lm in vertical height were clearly visible. Internal strain was also observed in normal and implanted vocal folds. Conclusions: Four-dimensional OCT of the vocal fold may help to more directly relate biomechanics to anatomy and disease. It may also be useful for assaying the functional rheology of implants in the context of real tissue. With further development, this technology has potential for clinical endoscopic application.

Objectives/Hypothesis: To explore whether adipose-derived stem/stromal cells (ASCs) have therapeutic potential for treating scarred superficial lamina propria through the effects of secreted hepatocyte growth factor (HGF) on scar fibroblasts. Study Design: In vitro study using coculture system. Methods: Scar fibroblasts (SFs) were isolated from ferret vocal folds electrocauterized 2 weeks previously. ASCs were isolated from ferret lipoaspirated subcutaneous abdominal fat. For coculture experiments, the two cell types were combined in Transwell plates for 6 days, followed by 1 or 3 days of monoculture after removing the upper chamber. Assays were then performed on cells and media from the bottom chamber. We measured: 1) the production of healuronic acid (HA), collagen and HGF via enzymelinked immunosorbent assays, 2) the expression of α-smooth muscle actin (α-SMA), 3) cell proliferation, and 4) apoptosis of SFs (2, 3, and 4 via flow cytometry). Other experiments examined the effects of HGF on SFs and the effects of HGF neutralization in the coculture system. Results: Coculture led to significant decreases in SF collagen production (P < .05), cell proliferation (P < .05), and α-SMA expression (P < .05), whereas HA production increased (P < .05). Coculture also increased HGF secretion from ASCs (P < .05). Neutralization of HGF abolished the inhibitory effects of ASCs on SF collagen synthesis (P < .05). Conclusions: ASCs influence SFs to adopt a less fibrotic profile. It appears that HGF is at least one of the soluble factors responsible for this effect. Implanted ASCs could potentially ameliorate vocal fold scar by acting as long-term, intrinsic sources of HGF.

Objectives/Hypothesis: High-resolution imaging of vocal folds that distinguishes vocal fold (VF) layered microstructure and VF implants would provide a key experimental tool for translational research investigating biomaterial-based interventions to treat vocal fold scar. To establish proof of concept, we studied whether 11.7 Tesla (T) magnetic resonance (MR) microimaging provides the needed resolution to resolve vocal fold tissue architecture. Study Design: We performed ex vivo MR microimaging of fixed ferret and canine larynges to determine whether changes in the layered architecture can be detected in the presence of scar and subsequent to biomaterial injections into the vocal folds. Serial section histological analyses were done to corroborate MR microimaging findings. Methods: Multiple axial and transverse/coronal 300-μm slices were obtained using an 11.7 T MR spectrometer/500 MHz for proton with gradient-recalled echo and rapid acquisition with relaxation enhancement imaging sequences. Results: High-resolution (39 μm/pixel) MR microimages distinguished VF epithelium, lamina propria, muscle, and cartilage in ferret and canine larynges. In ferret scarred VFs (n = 25), collagen-rich dense scar tissue was distinguishable from contralateral nonscarred VFs and from normal ferret VFs (n = 25), as confirmed on histology. MR microimaging accurately detected injected autologous fat, hyaluronic acid-based and polyethylene glycol (PEG)-based implants injected into both ferret and canine VFs. Importantly, MRI accurately showed resorption of PEG implants in ferrets and canines, as confirmed on histology. Additionally, ex vivo MR spectroscopy distinguished fat from PEG-based implants. Conclusions: Ex vivo 11.7 T MR microimaging provided high-resolution images of ferret and canine laryngeal tissue microstructure, although the superficial lamina propria could not be distinguished. Histology confirmed MR microimaging findings, indicating utility of MR microimaging of modeled scar, implant residence time, and tissue responses, thus providing integrative insight relevant to translational research. Laryngoscope, 2009

Objectives/Hypothesis: Optical coherence tomography (OCT) is a promising new imaging modality that can help discern the layered microstructure of vocal folds. In the future, subepithelial injections of implants will improve vocal fold pliability where there is stiffness of phonatory mucosa. Using OCT both to delineate the depth of subepithelial injections real-time and to serially image the implant over time would be valuable, and has not been demonstrated previously. Study Design: Ex vivo study using excised calf larynges and survival study using canines in vivo. Methods: An investigation was done employing real-time OCT imaging of subepithelial injection pulses into phonatory mucosa of four calf larynges ex vivo to track the presence of subepithelial implants in phonatory mucosa in a survival study using an in vivo canine model. Results: OCT readily identified polyethylene glycol (PEG)-based hydrogel in the subepithelial plane in both the ex vivo calf study and the in vivo canine study. Ex vivo calf images correlated with histological specimens obtained immediately postinjection. Images obtained in this study provide confirmation of the hydrogel injection depth in real time, and allow for the implant to be tracked during a canine survival study. Conclusions: OCT can confirm subepithelial placement of hydrogel implant in the vocal fold with sufficient resolution to provide instantaneous feedback of an injection pulse. Survival studies in an in vivo canine model indicate that OCT can potentially be helpful in monitoring rheologically appropriate implants within the superficial lamina propria. © 2009 The American Laryngological, Rhinological and Otological Society, Inc.

Controlling and guiding cell behavior requires scaffolding materials capable of programming the three-dimensional (3-D) extracellular environment. In this study, we devised a new self-assembling peptide template for synthesizing nanofibrous hydrogels containing cell-responsive ligands. In particular, the insertion of a matrix metalloproteinase-2 (MMP-2) labile hexapeptide into the self-assembling building blocks of arginine-alanine-aspartate-alanine (RADA) was investigated. A series of peptides, varied by the position of the MMP-2 hexapeptide substrate and the length of RADA blocks, were prepared by parallel synthesis. Their self-assembling capabilities were characterized and compared by circular dichroism spectroscopy and dynamical mechanical analysis. Among all the different insertion patterns, the sequence comprising a centrically positioned MMP-2 substrate was flanked with three RADA units on each side self-assembled into a hydrogel matrix, with mechanical properties and nanofiber morphology comparable to the native material built with (RADA)(4) alone. Exposure of the new gel to MMP-2 resulted in peptide cleavage, as confirmed by mass spectroscopy, and a decrease in surface hardness, as detected by nanoindentor, indicating that the enzyme mediated degradation was localized to the gel surface. The new design can be used for introducing biological functions into self-assembling peptides to create scaffolding materials with potential applications in areas such as tissue engineering and regenerative medicine.

Objectives: Evolving photoangiolytic laser techniques for treating vocal fold lesions motivated the development of a model for research and surgical training. The chick chorioallantoic membrane (CAM), which is composed of a microvasculature suspended within the egg albumen, simulates the vocal fold microcirculation within the superficial lamina propria (SLP). To characterize this model, we compared measurements of vessel diameters to superficial vessels in human vocal folds. Methods: The diameters of first-, second-, and third-order CAM vessels were measured in fertilized chicken eggs. The superficial blood vessels of the human vocal fold were measured from intraoperative images. Results: According to the branching pattern, vessel segments were identified as first-, second-, or third-order, with average diameters of 0.035 mm (0.02 to 0.1 mm), 0.18 mm (0.12 to 0.41 mm), and 0.8 mm (0.6 to 0.98 mm), respectively. The total vessels measured included 362 first-order, 119 second-order, and 82 third-order vessels. In 10 adult human vocal folds, an average vessel diameter of 0.04 mm (0.015 to 0.1 mm) was observed in 50 vessels. Conclusions: The CAM microvasculature suspended in albumen provides a useful surgical model simulating the microcirculation within the SLP of the human vocal fold. Although first-order CAM vessels best approximate the size of normal vocal fold subepithelial vessels seen at surgery, second- and third-order vessels resemble the vascular abnormalities frequently encountered during microsurgery for phonotraumatic lesions.

Objectives: The 2-μm-wavelength thulium laser has recently been shown to be an effective cutting instrument in endolaryngeal surgery, although there is increased thermal trauma as compared with the carbon dioxide laser. This study investigated temperature changes and thermal trauma during thulium laser dissection of laryngeal tissue, with and without air cooling, in an ex vivo model. Methods: A continuous-wave thulium laser (400-μm fiber, 4-W continuous power, 4-second duration) was used to incise 10 calf vocal folds. Paired cooled and uncooled cuts were made in each fold with a dermatologic cooling device. A thermistor inserted into the glottic subepithelium was used to measure tissue temperatures. Thermal damage was analyzed histologically by measuring the depth of the zone of lactate dehydrogenase inactivation surrounding the mucosal incision. Results: The initial vocal fold temperature averaged 24.3°C without cooling and 4.4°C with cooling. The peak temperature during cutting averaged 59.1°C without cooling and 28.0°C with cooling. The thermal damage zone surrounding the cooled incisions was approximately 27% less than that surrounding the uncooled incisions. Conclusions: Air cooling can reduce the extent of thermal trauma associated with thulium laser surgery of the vocal folds, and the high-temperature plume generated during laser cutting is effectively cleared.

Objectives: Selective vascular ablation (photoangiolysis) using pulsed lasers that target hemoglobin is an effective treatment strategy for many vocal fold lesions. However, vessel rupture with extravasation of blood reduces selectivity for vessels, which is frequently observed with the 0.45-ms, 585-nm pulsed dye laser. Previous studies have shown that vessel rupture is the result of vaporization of blood, an event that varies with laser pulse width and pulse fluence (energy per unit area). Clinical observations using a 532-nm wavelength pulsed potassium-titanyl-phosphate (KTP) laser revealed less laser-induced hemorrhage than the pulsed dye laser. This study investigated settings for the pulsed KTP laser to achieve selective vessel destruction without rupture using the avian chorioallantoic membrane under conditions similar to flexible laryngoscopic delivery of the laser in clinical practice. Study Design: The chick chorioallantoic membrane offers convenient access to many small blood vessels similar in size to those targeted in human vocal fold. Using a 532-nm pulsed KTP laser, pulse width, pulse energy, and working distance from the optical delivery fiber were varied to assess influence on the ability to achieve vessel coagulation without vessel wall rupture. Methods: Thirdorder vessels (n = 135) were irradiated: Energy (471-550 mJ), pulse width (10, 15, 30 ms), and fiber-to-tissue distance (1 mm, 3 mm) were varied systematically. Results: Selective vessel destruction without vessel wall rupture was more often achieved by increasing pulse width, increasing the fiber-to-tissue distance, and decreasing energy. Vessel destruction without rupture was consistently achieved using 15- or 30-ms pulses with a fiber-to-tissue distance of 3 mm (pulse fluence of 13-16 J/cm 2 ). Conclusions: This study substantiates our clinical observation that a 532-nm pulsed KTP laser was effective for ablating microcirculation while minimizing vessel wall rupture and hemorrhage.

We demonstrate three-dimensional vocal fold imaging during phonation by integrating optical coherence tomography with high-speed videoendoscopy. Results from ex vivo larynx experiments yield reconstructed vocal fold surface contours for ten phases of periodic motion.

Objectives: The objectives were to assess the clinical performance and accuracy of a prototype fiberoptic transnasal laryngeal endoscope with an auxiliary optical system that allows images to be spatially calibrated. Methods: A novel fiberoptic endoscope was developed that projects green laser beams across the field of view from a separate optical channel. According to the location of the spots in the field of view, the images can be calibrated with a software routine. To assess its performance, we compared measurements of 14 lesions imaged with the calibrated endoscope and during microlaryngoscopy, where a calibration instrument was placed next to the lesions. Four clinicians measured lesion length, width, and area from the collected images. Results: The calibrated endoscope performed as well as current flexible fiberoptic laryngoscopes in terms of image quality and patient comfort. For lesions with well-defined borders, the error ranged from 14% to 23% for length, from 20% to 30% for width, and from 33% to 50% for area across observers. Factors contributing to larger errors in some subjects were identified. Conclusions: The calibrated endoscope is capable of providing useful sizing information for laryngeal structures, and these measures correspond quite well to more direct measurements in the operating room. Objective sizing of laryngeal lesions is complicated by subjective judgments of lesion boundaries, which can be indistinct in many cases.

Objectives: This study examines the collagen content and turnover in the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. Methods: The LP collagen levels were assessed by quantifying tissue hydroxyproline. Quantitative histology allowed evaluation of the collagen content in specific LP regions. Several collagen types and Two markers of collagen turnover were examined immunohistochemically. Results: Collagen made up 43.4% ± 2.6% of human LP total protein (TP), with men having approximately 30% higher collagen content than women (p > .024). The collagen levels in pigs (52.6% ± 1.9% of TP) and ferrets (29.8% ± 3.7% of TP), but not that in dogs (45.3% ± 1.2% of TP), varied significantly from that in humans (pigs, p > .016; ferrets, p > .011). Quantitative histology indicated marked interspecies differences in total collagen distribution. Collagen types I, III, and IV were detected in the LP, and spatially complex staining patterns were observed for the Two markers of collagen turnover studied. Conclusions: The collagen content of the human LP is approximately 60% to 70% of that of human dermis. Although canine LP collagen levels are most similar to those of humans, quantitative histology indicates that the collagen distribution of the human LP is best matched by the porcine LP. Collagen types I and III seem to be the dominant LP collagens. Spatial variations in collagen turnover appear to exist that may contribute to normal LP physiology.

Objectives: Intraoperative assessment of vocal fold vibration during phonomicrosurgery performed under general anesthesia may enhance surgical decision-making. We therefore developed and bench-tested a new device we refer to as the aerodynamic vocal fold driver (AVFD). Materials and Methods: The AVFD comprises a hand-held probe that uses airflow to drive individual vocal folds into phonatory-like vibration. This permits stroboscopic visualization of mucosal waves with simultaneous control of subglottal air pressure. In initial experiments to validate the technique, AVFD driven phonation and conventional whole-larynx phonation were compared using excised canine larynges (n = 14). Results: Single vocal fold phonation using the AVFD and whole larynx phonation yielded similar, positive correlations between subglottal pressure and both amplitude and frequency of vibration. Experiments simulating vocal fold scar-related mucosal stiffening by subepithelial injection of fixative showed the expected elevation of phonation threshold pressures as measured with the AVFD. Likewise, unilateral tissue compression injury disrupted vocal fold vibration, and the AVFD was useful for quantifying improvement in the damaged vocal fold after repair with injection of cross-linked hyaluronic acid gel. Conclusions: These results show that this new instrument has the potential to provide novel and useful information for laryngeal experimentation and to improve phonosurgery.

Objectives:We examined the proteoglycan (PG) and associated sulfated glycosaminoglycan (GAG) content of the midmembranous vocal fold lamina propria (LP) of humans, dogs, pigs, and ferrets.Methods:The LP PG levels were assessed indirectly by quantifying the associated sulfated GAGs, and immunohistochemical analyses of specific PGs and/or GAGs (PGs/GAGs) were conducted.Results:Sulfated GAGs constituted approximately (average ± SEM) 14.7 ±2.1 μg per milligram of tissue total protein in the human LP — similar to levels in canine, porcine, and ferret LPs (p > .05). Immunohistochemical analysis identified versican, chondroitin 4- and 6-sulfate, and heparan sulfate in the LP extracellular matrix — PGs/GAGs previously believed to be localized only intracellularly and in the basement membrane. Observations of PG/GAG staining patterns resulted in identification of microstructurally based subdivisions of canine, porcine, and ferret LPs.Conclusions:The sulfated GAG concentration in human LP was similar to that of dermis. In contrast to the interspecies similarity in LP sulfated GAG levels, immunohistochemical analysis indicated notable interspecies differences in specific PG/GAG distributions. Moreover, spatial variations in the presence of several PGs/GAGs were observed — variations that may be integral in maintaining normal LP physiology. Finally, the noted canine, porcine, and ferret LP subdivisions may yield insight into the adaptation of LP microstructure to the phonatory needs of each species.

Low power, radarlike electromagnetic (EM) wave sensors, operating in a homodyne interferometric mode, are being used to measure tissue motions in the human vocal tract during speech. However, when these and similar sensors are used in front of the laryngeal region during voiced speech, there remains an uncertainty regarding the contributions to the sensor signal from vocal fold movements versus those from pressure induced trachea-wall movements. Several signal-source hypotheses are tested by performing experiments with a subject who had undergone tracheostomy, and who still was able to phonate when her stoma was covered (e.g., with a plastic plate). Laser-doppler motion-measurements of the subject's posterior trachea show small tissue movements, about 15 microns, that do not contribute significantly to signals from presently used EM sensors. However, signals from the anterior wall do contribute. EM sensor and air-pressure measurements, together with 3-D EM wave simulations, show that EM sensors measure movements of the vocal folds very well. The simulations show a surprisingly effective guiding of EM waves across the vocal fold membrane, which, upon glottal opening, are interrupted and reflected. These measurements are important for EM sensor applications to speech signal de-noising, vocoding, speech recognition, and diagnostics.

Despite a well-recognized clinical need for a material to replace missing or damaged vibratory connective tissue of the vocal fold, materials have yet to be engineered specifically for this purpose. Injectable hydrogels are particularly attractive because they would require a minimally invasive surgical procedure, could fill irregular defects, and could be designed to have viscoelastic properties similar to the normal tissue. We therefore synthesized a series of photo-cross-linkable hydrogels using hyaluronic acid (HA) as the starting material. The hydrogel precursors studied included HA modified with glycidyl methacrylate (HA/GMA), HA partially oxidized by sodium periodate (HAox) followed by GMA conjugation (HAox/GMA), and HA grafted with a synthetic polymer before introduction of GMA. The synthetic polymer employed was oligomeric poly(2-hydroxyethyl methacrylate) (P(HEMA)) with 31 mol % poly(N,N-dimethylacrylamide) (P(DMAM)), and the resulting hydrogel precursors were referred to as (HAox-g-Py)/GMA (y%:...

Measurements of the neck frequency response function (NFRF), defined as the ratio of the spectrum of the estimated volume velocity that excites the vocal tract to the spectrum of the acceleration delivered to the neck wall, were made at three different positions on the necks of nine laryngectomized subjects (five males and four females) and four normal laryngeal speakers (two males and two females). A minishaker driven by broadband noise provided excitation to the necks of subjects as they configured their vocal tracts to mimic the production of the vowels /a/, /ae/, and /I/. The sound pressure at the lips was measured with a microphone and an impedance head mounted on the shaker measured the acceleration. The neck wall passed low-frequency sound energy better than high-frequency sound energy, and thus the NFRF was accurately modeled as a low-pass filter. The NFRFs of the different subject groups (female laryngeal, male laryngeal speakers, laryngectomized males, and laryngectomized females) differed from each other in terms of corner frequency and gain, with both types of male subjects presenting NFRFs with larger overall gains. In addition, there was a notable amount of intersubject variability within groups. Because the NFRF is an estimate of how sound energy passes through the neck wall, these results should aid in the design of improved neck-type electrolarynx devices.

Einleitung. Auser mit der Hochgeschwindigkeitsglottographie konnen auch mit Hilfe der Doppelbelichtungsstroboskopie quantitative Messungen der Stimmlippenschwingungen durchgefuhrt werden.Die physikalisch-technischen Prinzipien dieser neuen Technik werden vorgestellt. Methode. Zwei Spezialstroboskope werden im Master-und-Slave-Prinzip miteinander gekoppelt.Mit Hilfe von verschiedenfarbigen Lichtfiltern werden zeitlich versetzt Lichtblitze ausgesendet, die durch die Zeit/Ort-Verschiebung der sich bewegenden Strukturen zu einer Doppelkonturierung beitragen. Da das Ausmas der Doppelkonturierung durch die Geschwindigkeit der sich bewegenden Stimmlippenstrukturen determiniert wird, lassen sich mit der Doppelbelichtungsstroboskopie Aussagen uber Art und ortliche Abhangigkeit der Geschwindigkeit der Offnungs- und Schliesungsvorgange der Stimmlippen auf Filmsequenzen oder auf einem Einzelbild machen. Schlussfolgerung. Mit der Doppelbelichtungsstroboskopie werden quantitative Messungen des Schwingungsablaufs der Stimmlippen moglich.Zudem kann eine Dokumentation dieser Vorgange auf nur einem (Kranken)blatt erreicht werden.

Three methods (I-III) are presented to demonstrate how technical modifications in the use of stroboscopy-related techniques can be applied to further analyze vocal fold vibrations. (I) With double exposure videostroboscopy, dynamic properties of vocal folds can be visualized within one single image. This allows for estimations of horizontal vibratory velocity of the vocal fold margins. (II) Stroboscopic transillumination of the larynx makes it possible to localize initial vocal fold opening in the horizontal glottal plane and to visualize different vibratory opening patterns. Bidirectional color-coded endoscopic imaging of the larynx facilitates a semi-automated, digital measurement of the glottal area. (III) Stroboscopic illumination using four light emitting diodes (LEDs) clipped on a rigid endoscope and triggered by a portable 'pocket-sized', battery-powered electronic control device offers new prospects for performing stroboscopy outside of specialized clinical facilities.

During clinical voice assessment, laryngologists and speech-language pathologists rely heavily on laryngeal endoscopy with videostroboscopy to evaluate pathology and dysfunction of the vocal folds. The cost effectiveness, ease of use, and synchronized audio and visual feedback provided by videostroboscopic assessment serve to maintain its predominant clinical role in laryngeal imaging. However, significant drawbacks include only two-dimensional spatial imaging and the lack of subsurface morphological information. A novel endoscope will be presented that integrates optical coherence tomography that is spatially and temporally co-registered with laryngeal videoendoscopic technology through a common path probe. Optical coherence tomography is a non-contact, micron-resolution imaging technology that acts as a visual ultrasound that employs a scanning laser to measure reflectance properties at air-tissue and tissue-tissue boundaries. Results obtained from excised larynx experiments demonstrate enhanced visuali...