COVID-19 in the Clinic: Trial of an Aerosol Containment Mask for Endoscopic Clinic Procedures.

OBJECTIVE: Create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures which also provides nanoparticle-level protection to patients. STUDY DESIGN: Prospective feasibility study. SETTING: In-person testing with a novel ACM. METHODS: The mask was designed in Solidworks and 3-dimensional printed. Measurements were made on 100 consecutive clinic patients who underwent medically necessarily endoscopy, 50 rigid nasal and 50 flexible, by 9 surgeons. RESULTS: Of the 50 patients who underwent rigid nasal endoscopy with the ACM, 0 of 25 patients with the suction off and 0 of 25 patients with the suction on had evidence of leakage of 0.3 µm particles. Of the 50 patients who underwent flexible endoscopy with the ACM, 0 of 25 patients with the suction off and 0 of 25 patients with the suction on had evidence of leakage of 0.3 µm particles. In terms of comfort, 73% of patients found the ACM somewhat or very comfortable without suction, compared to 86% with the suction on. Surgeons were able to visualize all necessary anatomic areas in 98% of procedures. In 97% of procedures, the masks were able to be placed easily. CONCLUSION: ACM can accommodate rigid nasal and flexible endoscopes and may prevent leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. LEVEL OF EVIDENCE: The level of evidence is 2.

Multi-window approach enables two-fold improvement in OCT axial resolution with strong side-lobe suppression and improved phase sensitivity.

A common processing approach for optical coherence tomography (OCT) uses a window function (e.g., Hann or rectangular window) for spectral shaping prior to calculating the Fourier transform. Here we build on a multi-window approach [Opt. Express8, 5267 (2017)10.1364/BOE.8.005267] that enables improved resolution while still suppressing side-lobe intensity. The shape of the window function defines the trade-off between main-lobe width (resolution) and side-lobe intensity. We have extended the approach to include the interferometric phase for phase-sensitive applications like vibrometry and Doppler OCT. Using the Hann window as a reference, we show that 11 Taylor windows are sufficient to achieve 50% improvement in axial resolution, -31 dB side-lobe intensity, and 20% improvement in phase sensitivity with low computational cost.

Vector of motion measurements in the living cochlea using a 3D OCT vibrometry system.

Optical coherence tomography (OCT) has become an important tool for measuring the vibratory response of the living cochlea. It stands alone in its capacity to measure the intricate motion of the hearing organ through the surrounding otic capsule bone. Nevertheless, as an extension of phase-sensitive OCT, it is only capable of measuring motion along the optical axis. Hence, measurements are 1-D. To overcome this limitation and provide a measure of the 3-D vector of motion in the cochlea, we developed an OCT system with three sample arms in a single interferometer. Taking advantage of the long coherence length of our swept laser, we depth (frequency) encode the three channels. An algorithm to depth decode and coregister the three channels is followed by a coordinate transformation that takes the vibrational data from the experimental coordinate system to Cartesian or spherical polar coordinates. The system was validated using a piezo as a known vibrating element that could be positioned at various angles. The angular measurement on the piezo was shown to have an RMSE of ≤ 0.30° (5.2 mrad) with a standard deviation of the amplitude of ≤ 120 pm. Finally, we demonstrate the system for in vivo imaging by measuring the vector of motion over a volume image in the apex of the mouse cochlea.

COVID-19 in the Clinic: Aerosol Containment Mask for Endoscopic Otolaryngologic Clinic Procedures.

OBJECTIVE: To create an aerosol containment mask (ACM) that contains aerosols during common otolaryngologic endoscopic procedures while protecting patients from environmental aerosols. STUDY DESIGN: Bench testing. SETTING: Mannequin testing. METHODS: The mask was designed in SolidWorks and 3-dimensional printed. Mannequins were fitted with a nebulizer to generate aerosols. Commercial particle counters were used to measure mask performance. RESULTS: The ACM has 2 ports on either side for instruments and endoscopes, a port for a filter, and a port that can evacuate aerosols contained within the mask via a standard suction pump. The mask contained aerosols on a mannequin with and without facial hair when the suction was set to 18.5 L/min. Other types of masks demonstrated substantial aerosol leakage under similar conditions. In a subsequent experiment, the ACM contained aerosols generated by a nebulizer up to the saturation of the particle detector without measurable leakage with or without suction. CONCLUSION: The ACM will accommodate rigid and flexible endoscopes plus instruments and prevent leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. LEVEL OF EVIDENCE: 2.

COVID-19 in the Clinic: Human Testing of an Aerosol Containment Mask for Endoscopic Clinic Procedures.

OBJECTIVE: To create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures that also provides nanoparticle-level protection to patients. STUDY DESIGN: Prospective feasibility study . SETTING: In-person testing with a novel ACM. METHODS: The mask was designed in Solidworks and 3D printed. Measurements were made on 10 healthy volunteers who wore the ACM while reading the Rainbow Passage repeatedly and performing a forced cough or sneeze at 5-second intervals over 1 minute with an endoscope in place. RESULTS: There was a large variation in the number of aerosol particles generated among the volunteers. Only the sneeze task showed a significant increase compared with normal breathing in the 0.3-µm particle size when compared with a 1-tailed t test (P = .013). Both the 0.5-µm and 2.5-µm particle sizes showed significant increases for all tasks, while the 2 largest particle sizes, 5 and 10 µm, showed no significant increase (both P < .01). With the suction off, 3 of 30 events (2 sneeze events and 1 cough event) had increases in particle counts, both inside and outside the mask. With the suction on, 2 of 30 events had an increase in particle counts outside the mask without a corresponding increase in particle counts inside the mask. Therefore, these fluctuations in particle counts were determined to be due to random fluctuation in room particle levels. CONCLUSION: ACM will accommodate rigid and flexible endoscopes plus instruments and may prevent the leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. LEVEL OF EVIDENCE: 2.

Respiratory Particle Emission During Voice Assessment and Therapy Tasks in a Single Subject.

INTRODUCTION: SARS-CoV-2 is transmitted via respiratory particles. Respiratory particle emission is impacted by manner of breathing and voicing, as well as intersubject variability. Assessment and treatment of voice disorders may include tasks that increase respiratory particle emission beyond typical breathing and speaking. This could increase the risk of disease transmission via respiratory particles. METHODS: Respiratory particle emission was measured during a single-subject, repeated measures clinical simulation of acoustic and aerodynamic assessment and voice therapy tasks. An optical particle sizer was used to measure particle count (1-10 µm in diameter). Assessment and therapy tasks were completed in three conditions: (1) 15 cm from the device, (2) 1 m from the device, and (3) 1 m from the device with the subject wearing a surgical mask. RESULTS: Condition 1 generated the highest particle count, with a median of 5.1 (13) additional particles above baseline, which was statistically significant (U = 381.5, P= 0.002). In condition 1, therapy and acoustic tasks combined produced more particles compared to the baseline and speech tasks, with a median difference of 6.5 additional particles per time point (U = 309.0, P= 0.002). This difference was not significant for conditions 2 and 3. Peak particle generation occurred in specific phonatory tasks, which was most pronounced in condition 1. Voice therapy tasks during condition 1 generated the highest peaks of normalized total particles with classical singing and expiratory muscle strength training. There was a significant difference in the amount of particle generation between condition 1 and 2, with a median difference of 5.2 particles (U = 461.0, P= 0.002). The particle count difference between conditions 2 and 3 was 2.1 (U = 282.0, P= 0.292), and this difference was not significant. The normalized total particles were assessed over time for each condition. For all conditions, there was no significant accumulation of particles. CONCLUSIONS: For a single subject, production of voice assessment and therapy tasks combined resulted in an increased number of respiratory particles compared to speech and baseline (1-10 µm). EMST and classical singing generated the greatest concentration of particles. Respiratory particle counts were higher at 15 cm from the particle sizer compared to 1 m from the particle sizer, suggesting that physical distancing may reduce immediate clinician exposure to respiratory particles. Particle concentration did not accumulate over time.

In vivo functional imaging of the human middle ear with a hand-held optical coherence tomography device.

We describe an optical coherence tomography and vibrometry system designed for portable hand-held usage in the otology clinic on awake patients. The system provides clinically relevant point-of-care morphological imaging with 14-44 µm resolution and functional vibratory measures with sub-nanometer sensitivity. We evaluated various new approaches for extracting functional information including a multi-tone stimulus, a continuous chirp stimulus, and alternating air and bone stimulus. We also explored the vibratory response over an area of the tympanic membrane (TM) and generated TM thickness maps. Our results suggest that the system can provide real-time in vivo imaging and vibrometry of the ear and could prove useful for investigating otologic pathology in the clinic setting.

Dual-modality optical coherence tomography and frequency-domain fluorescence lifetime imaging microscope system for intravascular imaging.

SIGNIFICANCE: Detailed biochemical and morphological imaging of the plaque burdened coronary arteries holds the promise of improved understanding of atherosclerosis plaque development, ultimately leading to better diagnostics and therapies. AIM: Development of a dual-modality intravascular catheter supporting swept-source optical coherence tomography (OCT) and frequency-domain fluorescence lifetime imaging (FD-FLIM) of endogenous fluorophores with UV excitation. APPROACH: We instituted a refined approach to endoscope development that combines simulation in a commercial ray tracing program, fabrication, and a measurement method for optimizing ball-lens performance. With this approach, we designed and developed a dual-modality catheter endoscope based on a double-clad fiber supporting OCT through the core and fluorescence collection through the first cladding. We varied the relative percent of UV excitation launched into the core and first cladding to explore the potential resolution improvement for FD-FLIM. The developed catheter endoscope was optically characterized, including measurement of spatial resolution and fluorescent lifetimes of standard fluorophores. Finally, the system was demonstrated on fresh ex vivo human coronary arteries. RESULTS: The developed endoscope was shown to have optical performance similar to predictions derived from the simulation approach. The FLIM resolution can be improved by over a factor of 4 by primarily illuminating through the core rather than the first cladding. However, time-dependent solarization losses need to be considered when choosing the relative percentage. We ultimately chose to illuminate with 7% of the power transmitting through the core. The resulting catheter endoscope had 40-µm lateral resolution for OCT and <100 µm lateral resolution for FD-FLIM. Images of ex vivo coronary arteries are consistent with expectations based on histopathology. CONCLUSIONS: The results demonstrate that our approach for endoscope simulation produces reliable predictions of endoscope performance. Simulation results guided our development of a multimodal OCT/FD-FLIM catheter imaging system for investigating atherosclerosis in coronary arteries.

Methylene blue-filled biodegradable polymer particles as a contrast agent for optical coherence tomography.

Optical coherence tomography (OCT) images largely lack molecular information or molecular contrast. We address that issue here, reporting on the development of biodegradable micro and nano-spheres loaded with methylene blue (MB) as molecular contrast agents for OCT. MB is a constituent of FDA approved therapies and widely used as a dye in off-label clinical applications. The sequestration of MB within the polymer reduced toxicity and improved signal strength by drastically reducing the production of singlet oxygen and leuco-MB. The former leads to tissue damage and the latter to reduced image contrast. The spheres are also strongly scattering which improves molecular contrast signal localization and enhances signal strength. We demonstrate that these contrast agents may be imaged using both pump-probe OCT and photothermal OCT, using a 830 nm frequency domain OCT system and a 1.3 µm swept source OCT system. We also show that these contrast agents may be functionalized and targeted to specific receptors, e.g. the VCAM receptor known to be overexpressed in inflammation.

Picometer scale vibrometry in the human middle ear using a surgical microscope based optical coherence tomography and vibrometry system.

We have developed a highly phase stable optical coherence tomography and vibrometry system that attaches directly to the accessory area of a surgical microscope common to both the otology clinic and operating room. Careful attention to minimizing sources of phase noise has enabled a system capable of measuring vibrations of the middle ear with a sensitivity of < 5 pm in an awake human patient. The system is shown to be capable of collecting a wide range of information on the morphology and function of the ear in live subjects, including frequency tuning curves below the hearing threshold, maps of tympanic membrane vibrational modes and thickness, and measures of distortion products due to the nonlinearities in the cochlear amplifier.

Automated detection of superficial macrophages in atherosclerotic plaques using autofluorescence lifetime imaging.

BACKGROUND AND AIMS: Macrophages play an important role in the development and destabilization of advanced atherosclerotic plaques. Hence, the clinical imaging of macrophage content in advanced plaques could potentially aid in identifying patients most at risk of future clinical events. The lifetime of the autofluorescence emission from atherosclerotic plaques has been correlated with lipids and macrophage accumulation in ex vivo human coronary arteries, suggesting the potential of intravascular endogenous fluorescence or autofluorescence lifetime imaging (FLIM) for macrophage imaging. The aim of this study was to quantify the accuracy of the coronary intima autofluorescence lifetime to detect superficial macrophage accumulation in atherosclerotic plaques. METHODS: Endogenous FLIM imaging was performed on 80 fresh postmortem coronary segments from 23 subjects. The plaque autofluorescence lifetime at an emission spectral band of 494 ±â€¯20.5 nm was used as a discriminatory feature to detect superficial macrophage accumulation in atherosclerotic plaques. Detection of superficial macrophage accumulation in the imaged coronary segments based on immunohistochemistry (CD68 staining) evaluation was taken as the gold standard. Receiver Operating Characteristic (ROC) curve analysis was applied to select an autofluorescence lifetime threshold value to detect superficial macrophages accumulation. RESULTS: A threshold of 6 ns in the plaque autofluorescence lifetime at the emission spectral band of 494 ±â€¯20.5 nm was applied to detect plaque superficial macrophages accumulation, resulting in ∼91.5% accuracy. CONCLUSIONS: This study demonstrates the capability of endogenous FLIM imaging to accurately identify superficial macrophages accumulation in human atherosclerotic plaques, a key biomarker of atherosclerotic plaque vulnerability.

Endoscopic optical coherence tomography enables morphological and subnanometer vibratory imaging of the porcine cochlea through the round window.

A highly phase stable hand-held (HH) endoscopic system has been developed for optical coherence tomography and vibrometry. Designed to transit the ear canal to the middle ear space and peer through the round window (RW), it is capable of imaging the vibratory function of the cochlear soft tissues with subnanometer scale sensitivity. A side-looking, 9 cm long rigid endoscope with a distal diameter of 1.2 mm, was able to fit within the RW niche and provide imaging access. The phase stability was achieved in part by fully integrating a Michelson interferometer into the HH device. Ex vivo imaging of a domestic pig demonstrated the system's ability for functional vibratory imaging of the cochlea via the RW.

Enhanced coupling of light into a turbid medium through microscopic interface engineering.

There are many optical detection and sensing methods used today that provide powerful ways to diagnose, characterize, and study materials. For example, the measurement of spontaneous Raman scattering allows for remote detection and identification of chemicals. Many other optical techniques provide unique solutions to learn about biological, chemical, and even structural systems. However, when these systems exist in a highly scattering or turbid medium, the optical scattering effects reduce the effectiveness of these methods. In this article, we demonstrate a method to engineer the geometry of the optical interface of a turbid medium, thereby drastically enhancing the coupling efficiency of light into the material. This enhanced optical coupling means that light incident on the material will penetrate deeper into (and through) the medium. It also means that light thus injected into the material will have an enhanced interaction time with particles contained within the material. These results show that, by using the multiple scattering of light in a turbid medium, enhanced light-matter interaction can be achieved; this has a direct impact on spectroscopic methods such as Raman scattering and fluorescence detection in highly scattering regimes. Furthermore, the enhanced penetration depth achieved by this method will directly impact optical techniques that have previously been limited by the inability to deposit sufficient amounts of optical energy below or through highly scattering layers.

Lensless, ultra-wideband fiber optic rotary joint for biomedical applications.

The demands of optical fiber-based biomedical applications can, in many cases, outstrip the capabilities of lens-based commercially available fiber optic rotary joints. In some circumstances, it is necessary to use very broad spectral bandwidths (near UV to short-wave IR) and specialized optical fibers, such as double-clad fiber, and have the capacity to accommodate high rotational velocities. The broad spectrum, stretching down into the UV, presents two problems: (1) adequate chromatic correction in the lenses across the entire bandwidth and (2) strong UV absorption by the fluids used to lubricate the rotary joint. To accommodate these types of applications, we have developed an ultra-wideband lensless fiber optic rotary joint based on the principle that when two optical fibers are coaligned and placed in contact (or very close), the optical losses at the junction are very low. The advances demonstrated here enable excellent performance (<0.2 dB insertion loss), even down into the UV and spanning a wavelength range of at least 355-1360 nm with single-mode, multimode, and double-clad fibers. We also demonstrate excellent performance, ∼0.38 dB insertion loss, at rotational velocities up to 8800 rpm (146 Hz). To the best of our knowledge, this is the first demonstration of this type of rotary joint capable of such a wide bandwidth and high rotational velocities.

In vivo molecular contrast OCT imaging of methylene blue.

An 830-nm spectral-domain optical coherence tomography (OCT) system with an integrated 663-nm diode pump laser has been developed to enable molecular contrast OCT imaging of methylene blue (MB), a common vital dye used clinically. The introduction of the 663-nm diode laser, which acts as the pump in this implementation of pump-probe OCT (PPOCT), represents a minor modification to an otherwise typical OCT system. A newly developed background subtraction technique completely removes all background from intensity noise at the pump modulation frequency, simplifying the interpretation of PPOCT images. These developments have enabled the first in vivo imaging of MB with PPOCT. Volumetric images of a zebrafish, stained by submersion in a 0.01% (w/v) solution of MB for 6 h, show accumulation of MB in the mesonephros, the primordial filtration organ.

In vivo pump-probe optical coherence tomography imaging in Xenopus laevis.

Currently, optical coherence tomography (OCT), is not capable of obtaining molecular information often crucial for identification of disease. To enable molecular imaging with OCT, we have further developed a technique that harnesses transient changes in light absorption in the sample to garner molecular information. A Fourier-domain Pump-Probe OCT (PPOCT) system utilizing a 532 nm pump and 830 nm probe has been developed for imaging hemoglobin. Methylene blue, a biological dye with well-know photophysics, was used to characterize the system before investigating the origin of the hemoglobin PPOCT signal. The first in vivo PPOCT images were recorded of the vasculature in Xenopus laevis. The technique was shown to work equally well in flowing and nonflowing vessels. Furthermore, PPOCT was compared with other OCT extensions which require flow, such as Doppler OCT and phase-variance OCT. PPOCT was shown to better delineate tortuous vessels, where nodes often restrict Doppler and phase-variance reconstruction.

Molecular Imaging in Optical Coherence Tomography.

Optical coherence tomography (OCT) is a medical imaging technique that provides tomographic images at micron scales in three dimensions and high speeds. The addition of molecular contrast to the available morphological image holds great promise for extending OCT's impact in clinical practice and beyond. Fundamental limitations prevent OCT from directly taking advantage of powerful molecular processes such as fluorescence emission and incoherent Raman scattering. A wide range of approaches is being researched to provide molecular contrast to OCT. Here we review those approaches with particular attention to those that derive their molecular contrast directly from modulation of the OCT signal. We also provide a brief overview of the multimodal approaches to gaining molecular contrast coincident with OCT.

Fluorescence imaging of latent fingerprints on conjugated polymer films with large fractional free volume.

When a fluorescent conjugated polymer film of PTMSDPA with an extremely large fractional free volume was directly or indirectly contacted to latent fingerprints, high resolution fluorescence images were obtained.