Ultra-miniature dual-wavelength spatial frequency domain imaging for micro-endoscopy.

Significance: There is a need for a cost-effective, quantitative imaging tool that can be deployed endoscopically to better detect early stage gastrointestinal cancers. Spatial frequency domain imaging (SFDI) is a low-cost imaging technique that produces near-real time, quantitative maps of absorption and reduced scattering coefficients, but most implementations are bulky and suitable only for use outside the body. Aim: We aim to develop an ultra-miniature SFDI system comprising an optical fiber array (diameter 0.125 mm) and a micro camera (1×1 mm package) to displace conventionally bulky components, in particular, the projector. Approach: First, we fabricated a prototype with an outer diameter of 3 mm, although the individual component dimensions could permit future packaging to a <1.5 mm diameter. We developed a phase-tracking algorithm to rapidly extract images with fringe projections at three equispaced phase shifts to perform SFDI demodulation. Results: To validate the performance, we first demonstrate comparable recovery of quantitative optical properties between our ultra-miniature system and a conventional bench-top SFDI system with an agreement of 15% and 6% for absorption and reduced scattering, respectively. Next, we demonstrate imaging of absorption and reduced scattering of tissue-mimicking phantoms providing enhanced contrast between simulated tissue types (healthy and tumour), done simultaneously at wavelengths of 515 and 660 nm. Using a support vector machine classifier, we estimate that sensitivity and specificity values of >90% are feasible for detecting simulated squamous cell carcinoma. Conclusions: This device shows promise as a cost-effective, quantitative imaging tool to detect variations in optical absorption and scattering as indicators of cancer.

Cytosponge procedures produce fewer respiratory aerosols and droplets than esophagogastroduodenoscopies.

Esophagogastroduodenoscopies (EGD) are aerosol-generating procedures that may spread respiratory pathogens. We aim to investigate the production of airborne aerosols and droplets during Cytosponge procedures, which are being evaluated in large-scale research studies and National Health Service (NHS)implementation pilots to reduce endoscopy backlogs. We measured 18 Cytosponge and 37 EGD procedures using a particle counter (diameters = 0.3-25 µm), taking measurements 10 cm from the mouth. Two particle count analyses were performed: whole procedure and event-based. Direct comparison with duration-standardized EGD procedures shows that Cytosponge procedures produce 2.16× reduction (P < 0.001) for aerosols and no significant change for droplets (P = 0.332). Event-based analysis shows that particle production is driven by throat spray (aerosols: 138.1× reference, droplets: 16.2×), which is optional, and removal of Cytosponge (aerosols: 14.6×, droplets: 62.6×). Cytosponge burping produces less aerosols than EGD (2.82×, P < 0.05). Cytosponge procedures produce significantly less aerosols and droplets than EGD procedures and thus reduce two potential transmission routes for respiratory viruses.

Designing and simulating realistic spatial frequency domain imaging systems using open-source 3D rendering software.

Spatial frequency domain imaging (SFDI) is a low-cost imaging technique that maps absorption and reduced scattering coefficients, offering improved contrast for important tissue structures such as tumours. Practical SFDI systems must cope with various imaging geometries including imaging planar samples ex vivo, imaging inside tubular lumen in vivo e.g. for endoscopy, and measuring tumours or polyps of varying morphology. There is a need for a design and simulation tool to accelerate design of new SFDI systems and simulate realistic performance under these scenarios. We present such a system implemented using open-source 3D design and ray-tracing software Blender that simulates media with realistic absorption and scattering in a wide range of geometries. By using Blender's Cycles ray-tracing engine, our system simulates effects such as varying lighting, refractive index changes, non-normal incidence, specular reflections and shadows, enabling realistic evaluation of new designs. We first demonstrate quantitative agreement between Monte-Carlo simulated absorption and reduced scattering coefficients with those simulated from our Blender system, achieving 16% discrepancy in absorption coefficient and 18% in reduced scattering coefficient. However, we then show that using an empirically derived look-up table the errors reduce to 1% and 0.7% respectively. Next, we simulate SFDI mapping of absorption, scattering and shape for simulated tumour spheroids, demonstrating enhanced contrast. Finally we demonstrate SFDI mapping inside a tubular lumen, which highlighted a important design insight: custom look-up tables must be generated for different longitudinal sections of the lumen. With this approach we achieved 2% absorption error and 2% scattering error. We anticipate our simulation system will aid in the design of novel SFDI systems for key biomedical applications.

Aerosol and droplet generation in upper and lower GI endoscopy: whole procedure and event-based analysis.

BACKGROUND AND AIMS: Aerosol-generating procedures have become an important healthcare issue during the coronavirus disease 2019 (COVID-19) pandemic because the severe acute respiratory syndrome coronavirus 2 virus can be transmitted through aerosols. We aimed to characterize aerosol and droplet generation in GI endoscopy, where there is little evidence. METHODS: This prospective observational study included 36 patients undergoing routine peroral gastroscopy (POG), 11 undergoing transnasal endoscopy (TNE), and 48 undergoing lower GI (LGI) endoscopy. Particle counters took measurements near the appropriate orifice (2 models were used with diameter ranges of .3-25 µm and 20-3000 µm). Quantitative analysis was performed by recording specific events and subtracting background particles. RESULTS: POG produced 1.96 times the level of background particles (P < .001) and TNE produced 2.00 times (P < .001), but a direct comparison showed POG produced 2.00 times more particles than TNE. LGI procedures produced significant particle counts (P < .001) with 2.4 times greater production per procedure than POG but only .63 times production per minute. Events that were significant relative to the room background particle count were POG, with throat spray (150.0 times, P < .001), esophageal extubation (37.5 times, P < .001), and coughing or gagging (25.8 times, P < .01); TNE, with nasal spray (40.1 times, P < .001), nasal extubation (32.0 times, P < .01), and coughing or gagging (20.0, P < .01); and LGI procedures, with rectal intubation (9.9 times, P < .05), rectal extubation (27.2 times, P < .01), application of abdominal pressure (9.6 times, P < .05), and rectal insufflation or retroflexion (7.7 times, P < .01). These all produced particle counts larger than or comparable with volitional cough. CONCLUSIONS: GI endoscopy performed through the mouth, nose, or rectum generates significant quantities of aerosols and droplets. Because the infectivity of procedures is not established, we therefore suggest adequate personal protective equipment is used for all GI endoscopy where there is a high population prevalence of COVID-19. Avoiding throat and nasal spray would significantly reduce particles generated from upper GI procedures.

Quantitative phase and polarization imaging through an optical fiber applied to detection of early esophageal tumorigenesis.

Phase and polarization of coherent light are highly perturbed by interaction with microstructural changes in premalignant tissue, holding promise for label-free detection of early tumors in endoscopically accessible tissues such as the gastrointestinal tract. Flexible optical multicore fiber (MCF) bundles used in conventional diagnostic endoscopy and endomicroscopy scramble phase and polarization, restricting clinicians instead to low-contrast amplitude-only imaging. We apply a transmission matrix characterization approach to produce full-field en-face images of amplitude, quantitative phase, and resolved polarimetric properties through an MCF. We first demonstrate imaging and quantification of biologically relevant amounts of optical scattering and birefringence in tissue-mimicking phantoms. We present an entropy metric that enables imaging of phase heterogeneity, indicative of disordered tissue microstructure associated with early tumors. Finally, we demonstrate that the spatial distribution of phase and polarization information enables label-free visualization of early tumors in esophageal mouse tissues, which are not identifiable using conventional amplitude-only information.

A clinically translatable hyperspectral endoscopy (HySE) system for imaging the gastrointestinal tract.

Hyperspectral imaging (HSI) enables visualisation of morphological and biochemical information, which could improve disease diagnostic accuracy. Unfortunately, the wide range of image distortions that arise during flexible endoscopy in the clinic have made integration of HSI challenging. To address this challenge, we demonstrate a hyperspectral endoscope (HySE) that simultaneously records intrinsically co-registered hyperspectral and standard-of-care white light images, which allows image distortions to be compensated computationally and an accurate hyperspectral data cube to be reconstructed as the endoscope moves in the lumen. Evaluation of HySE performance shows excellent spatial, spectral and temporal resolution and high colour fidelity. Application of HySE enables: quantification of blood oxygenation levels in tissue mimicking phantoms; differentiation of spectral profiles from normal and pathological ex vivo human tissues; and recording of hyperspectral data under freehand motion within an intact ex vivo pig oesophagus model. HySE therefore shows potential for enabling HSI in clinical endoscopy.

Reconstruction of Optical Vector-Fields With Applications in Endoscopic Imaging.

We introduce a framework for the reconstruction of the amplitude, phase, and polarization of an optical vector-field using measurements acquired by an imaging device characterized by an integral transform with an unknown spatially variant kernel. By incorporating effective regularization terms, this new approach is able to recover an optical vector-field with respect to an arbitrary representation system, which may be different from the one used for device calibration. In particular, it enables the recovery of an optical vector-field with respect to a Fourier basis, which is shown to yield indicative features of increased scattering associated with tissue abnormalities. We demonstrate the effectiveness of our approach using synthetic holographic images and biological tissue samples in an experimental setting, where the measurements of an optical vector-field are acquired by a multicore fiber endoscope, and observe that indeed the recovered Fourier coefficients are useful in distinguishing healthy tissues from tumors in early stages of oesophageal cancer.

Bimodal reflectance and fluorescence multispectral endoscopy based on spectrally resolving detector arrays.

Emerging clinical interest in combining standard white light endoscopy with targeted near-infrared (NIR) fluorescent contrast agents for improved early cancer detection has created demand for multimodal imaging endoscopes. We used two spectrally resolving detector arrays (SRDAs) to realize a bimodal endoscope capable of simultaneous reflectance-based imaging in the visible spectral region and multiplexed fluorescence-based imaging in the NIR. The visible SRDA was composed of 16 spectral bands, with peak wavelengths in the range of 463 to 648 nm and full-width at half-maximum (FWHM) between 9 and 26 nm. The NIR SRDA was composed of 25 spectral bands, with peak wavelengths in the range 659 to 891 nm and FWHM 7 to 15 nm. The spectral endoscope design was based on a "babyscope" model using a commercially available imaging fiber bundle. We developed a spectral transmission model to select optical components and provide reference endmembers for linear spectral unmixing of the recorded image data. The technical characterization of the spectral endoscope is presented, including evaluation of the angular field-of-view, barrel distortion, spatial resolution and spectral fidelity, which showed encouraging performance. An agarose phantom containing oxygenated and deoxygenated blood with three fluorescent dyes was then imaged. After spectral unmixing, the different chemical components of the phantom could be successfully identified via majority decision with high signal-to-background ratio (>3). Imaging performance was further assessed in an ex vivo porcine esophagus model. Our preliminary imaging results demonstrate the capability to simultaneously resolve multiple biological components using a compact spectral endoscopy system.