Kevin Woods

Endoscopic probe optics for spectrally encoded confocal microscopy.

Spectrally encoded confocal microscopy (SECM) is a form of reflectance confocal microscopy that can achieve high imaging speeds using relatively simple probe optics. Previously, the feasibility of conducting large-area SECM imaging of the esophagus in bench top setups has been demonstrated. Challenges remain, however, in translating SECM into a clinically-useable device; the tissue imaging performance should be improved, and the probe size needs to be significantly reduced so that it can fit into luminal organs of interest. In this paper, we report the development of new SECM endoscopic probe optics that addresses these challenges. A custom water-immersion aspheric singlet (NA = 0.5) was developed and used as the objective lens. The water-immersion condition was used to reduce the spherical aberrations and specular reflection from the tissue surface, which enables cellular imaging of the tissue deep below the surface. A custom collimation lens and a small-size grating were used along with the custom aspheric singlet to reduce the probe size. A dual-clad fiber was used to provide both the single- and multi- mode detection modes. The SECM probe optics was made to be 5.85 mm in diameter and 30 mm in length, which is small enough for safe and comfortable endoscopic imaging of the gastrointestinal tract. The lateral resolution was 1.8 and 2.3 µm for the single- and multi- mode detection modes, respectively, and the axial resolution 11 and 17 µm. SECM images of the swine esophageal tissue demonstrated the capability of this device to enable the visualization of characteristic cellular structural features, including basal cell nuclei and papillae, down to the imaging depth of 260 µm. These results suggest that the new SECM endoscopic probe optics will be useful for imaging large areas of the esophagus at the cellular scale in vivo.

Spectrally encoded confocal microscopy of esophageal tissues at 100 kHz line rate

Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that uses a diffraction grating to illuminate different locations on the sample with distinct wavelengths. SECM can obtain line images without any beam scanning devices, which opens up the possibility of high-speed imaging with relatively simple probe optics. This feature makes SECM a promising technology for rapid endoscopic imaging of internal organs, such as the esophagus, at microscopic resolution. SECM imaging of the esophagus has been previously demonstrated at relatively low line rates (5 kHz). In this paper, we demonstrate SECM imaging of large regions of esophageal tissues at a high line imaging rate of 100 kHz. The SECM system comprises a wavelength-swept source with a fast sweep rate (100 kHz), high output power (80 mW), and a detector unit with a large bandwidth (100 MHz). The sensitivity of the 100-kHz SECM system was measured to be 60 dB and the transverse resolution was 1.6 µm. Excised swine and human esophageal tissues were imaged with the 100-kHz SECM system at a rate of 6.6 mm(2)/sec. Architectural and cellular features of esophageal tissues could be clearly visualized in the SECM images, including papillae, glands, and nuclei. These results demonstrate that large-area SECM imaging of esophageal tissues can be successfully conducted at a high line imaging rate of 100 kHz, which will enable whole-organ SECM imaging in vivo.

Attentive Tracking of Sound Sources

Auditory scenes often contain concurrent sound sources, but listeners are typically interested in just one of these and must somehow select it for further processing. One challenge is that real-world sounds such as speech vary over time and as a consequence often cannot be separated or selected based on particular values of their features (e.g., high pitch). Here we show that human listeners can circumvent this challenge by tracking sounds with a movable focus of attention. We synthesized pairs of voices that changed in pitch and timbre over random, intertwined trajectories, lacking distinguishing features or linguistic information. Listeners were cued beforehand to attend to one of the voices. We measured their ability to extract this cued voice from the mixture by subsequently presenting the ending portion of one voice and asking whether it came from the cued voice. We found that listeners could perform this task but that performance was mediated by attention-listeners who performed best were also more sensitive to perturbations in the cued voice than in the uncued voice. Moreover, the task was impossible if the source trajectories did not maintain sufficient separation in feature space. The results suggest a locus of attention that can follow a sounds trajectory through a feature space, likely aiding selection and segregation amid similar distractors.

Headphone screening to facilitate web-based auditory experiments

Psychophysical experiments conducted remotely over the internet permit data collection from large numbers of participants but sacrifice control over sound presentation and therefore are not widely employed in hearing research. To help standardize online sound presentation, we introduce a brief psychophysical test for determining whether online experiment participants are wearing headphones. Listeners judge which of three pure tones is quietest, with one of the tones presented 180° out of phase across the stereo channels. This task is intended to be easy over headphones but difficult over loudspeakers due to phase-cancellation. We validated the test in the lab by testing listeners known to be wearing headphones or listening over loudspeakers. The screening test was effective and efficient, discriminating between the two modes of listening with a small number of trials. When run online, a bimodal distribution of scores was obtained, suggesting that some participants performed the task over loudspeakers despite instructions to use headphones. The ability to detect and screen out these participants mitigates concerns over sound quality for online experiments, a first step toward opening auditory perceptual research to the possibilities afforded by crowdsourcing.

Comprehensive confocal endomicroscopy of the esophagus in vivo

Background and study aims: Biopsy sampling error can be a problem for the diagnosis of certain gastrointestinal tract diseases. Spectrally-encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has the potential to overcome sampling error by imaging large regions of gastrointestinal tract tissues. The aim of this study was to test a recently developed SECM endoscopic probe for comprehensively imaging large segments of the esophagus at the microscopic level in vivo. Methods: Topical acetic acid was endoscopically applied to the esophagus of a normal living swine. The 7 mm diameter SECM endoscopic probe was transorally introduced into the esophagus over a wire. Optics within the SECM probe were helically scanned over a 5 cm length of the esophagus. Confocal microscopy data was displayed and stored in real time. Results: Very large confocal microscopy images (length = 5 cm; circumference = 2.2 cm) of swine esophagus from three imaging depths, spanning a total area of 33 cm2, were obtained in about 2 minutes. SECM images enabled the visualization of cellular morphology of the swine esophagus, including stratified squamous cell nuclei, basal cells, and collagen within the lamina propria. Conclusions: The results from this study suggest that the SECM technology can rapidly provide large, contiguous confocal microscopy images of the esophagus in vivo. When applied to human subjects, the unique comprehensive, microscopic imaging capabilities of this technology may be utilized for improving the screening and surveillance of various esophageal diseases.

Schema learning for the cocktail party problem

Significance The “cocktail party problem” is encountered when sounds from different sources in the world mix in the air before arriving at the ear, requiring the brain to estimate individual sources from the received mixture. Sounds produced by a given source often exhibit consistencies in structure that might be useful for separating sources if they could be learned. Here we show that listeners rapidly learn the abstract structure shared by sounds from novel sources and use the learned structure to extract these sounds when they appear in mixtures. The involvement of learning and memory in our ability to hear one sound among many opens an avenue to understanding the role of statistical regularities in auditory scene analysis. The cocktail party problem requires listeners to infer individual sound sources from mixtures of sound. The problem can be solved only by leveraging regularities in natural sound sources, but little is known about how such regularities are internalized. We explored whether listeners learn source “schemas”—the abstract structure shared by different occurrences of the same type of sound source—and use them to infer sources from mixtures. We measured the ability of listeners to segregate mixtures of time-varying sources. In each experiment a subset of trials contained schema-based sources generated from a common template by transformations (transposition and time dilation) that introduced acoustic variation but preserved abstract structure. Across several tasks and classes of sound sources, schema-based sources consistently aided source separation, in some cases producing rapid improvements in performance over the first few exposures to a schema. Learning persisted across blocks that did not contain the learned schema, and listeners were able to learn and use multiple schemas simultaneously. No learning was evident when schema were presented in the task-irrelevant (i.e., distractor) source. However, learning from task-relevant stimuli showed signs of being implicit, in that listeners were no more likely to report that sources recurred in experiments containing schema-based sources than in control experiments containing no schema-based sources. The results implicate a mechanism for rapidly internalizing abstract sound structure, facilitating accurate perceptual organization of sound sources that recur in the environment.

Pilot Clinical Trial of Indocyanine Green Fluorescence-Augmented Colonoscopy in High Risk Patients

White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15–25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1) the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2) the ability of this system to identify polyps as small as 1 mm, and (3) the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps.

Rapid learning of sound schema for the cocktail party problem

Auditory scene analysis depends on knowledge of natural sound structure, but little is known about how source-specific structures might be learned and applied. We explored whether listeners internalize “schemas”—the abstract structure shared by different occurrences of the same type of sound source—during cocktail-party listening. We measured the ability to detect one of two concurrent “melodies” that did not differ in mean pitch (nor in timbre), ensuring that only the structure of these melodies over time could be used to distinguish them. Target melodies were cued by presenting them in isolation before each mixture, transposed to avoid exact repetition. The task was to determine if the cued melody was present in the subsequent mixture. Listeners performed above chance despite transposition between cue and target. Particular melodic schemas could recur across a subset of trials within a block, as well as across blocks separated by epochs in which the schema was absent. Recurrence across trials within a b...

Attentive tracking in human audition

Auditory scenes often contain multiple sound sources, but typically one is of particular interest and must be selected for further processing. This “cocktail party problem” is especially difficult when sources are similar and change over time (e.g., speakers of the same gender). To study this situation, we introduced a paradigm in which listeners attempt to follow one of two synthetic voices that vary randomly in several feature dimensions (e.g., f0, f1, and f2). Psychophysical results from this task suggest that human listeners employ a movable focus of attention that follows sources of interest through their feature space. Here we utilize this paradigm to probe the performance limits of attentive tracking. We also report that listeners can learn the abstract “shape” of an attentively tracked trajectory if it occurs repeatedly in a stimulus set. Knowledge of trajectory regularities appears to benefit the tracking of target sources, and demonstrates another way in which attentive tracking might aid our ab...