All-reflective tethered capsule endoscope for multimodal optical coherence tomography in the esophagus.

Significance: Esophageal cancer is becoming increasingly prevalent in Western countries. Early detection is crucial for effective treatment. Multimodal imaging combining optical coherence tomography (OCT) with complementary optical imaging techniques may provide enhanced diagnostic capabilities by simultaneously assessing tissue morphology and biochemical content. Aim: We aim to develop a tethered capsule endoscope (TCE) that can accommodate a variety of point-scanning techniques in addition to OCT without requiring design iterations on the optical or mechanical design. Approach: We propose a TCE utilizing exclusively reflective optics to focus and steer light from and to a double-clad fiber. Specifically, we use an ellipsoidal mirror to achieve finite conjugation between the fiber tip and the imaging plane. Results: We demonstrate a functional all-reflective TCE. We first detail the design, fabrication, and assembly steps required to obtain such a device. We then characterize its performance and demonstrate combined OCT at 1300 nm and visible spectroscopic imaging in the 500- to 700-nm range. Finally, we discuss the advantages and limitations of the proposed design. Conclusions: An all-reflective TCE is feasible and allows for achromatic high-quality imaging. Such a device could be utilized as a platform for testing various combinations of modalities to identify the optimal candidates without requiring design iterations.

MCOCT: an experimentally and numerically validated, open-source Monte Carlo simulator for optical coherence tomography.

Here, we present MCOCT, a Monte Carlo simulator for optical coherence tomography (OCT), incorporating a Gaussian illumination scheme and bias to increase backscattered event collection. MCOCT optical fluence was numerically compared and validated to an established simulator (MCX) and showed concordance at the focus while diverging slightly with distance to it. MCOCT OCT signals were experimentally compared and validated to OCT signals acquired in tissue-mimicking phantoms with known optical properties and showed a similar attenuation pattern with increasing depth while diverging beyond 1.5 mm and proximal to layer interfaces. MCOCT may help in the design of OCT systems for a wide range of applications.

Impact of Cleaning on Membrane Performance during Surface Water Treatment: A Hybrid Process with Biological Ion Exchange and Gravity-Driven Membranes.

In this study, the hybrid biological ion exchange (BIEX) resin and gravity-driven membrane (GDM) process was employed for the treatment of coloured and turbid river water. The primary objective was to investigate the impact of both physical and chemical cleaning methods on ceramic and polymeric membranes in terms of their stabilised flux, flux recovery after physical/chemical cleaning, and permeate quality. To address these objectives, two types of MF and UF membranes were utilised (M1 = polymeric MF, M2 = polymeric UF, M3 = ceramic UF, and M4 = lab-made ceramic MF). Throughout the extended operation, the resin functioned initially in the primary ion exchange (IEX) region (NOM displacement with pre-charged chloride) and progressed to a secondary IEX stage (NOM displacement with bicarbonate and sulphate), while membrane flux remained stable. Subsequently, physical cleaning involved air/water backwash with two different flows and pressures, and chemical cleaning utilised NaOH at concentrations of 20 and 40 mM, as well as NaOCl at concentrations of 250 and 500 mg Cl2/L. These processes were carried out to assess flux recovery and identify fouling reversibility. The results indicate an endpoint of 1728 bed volumes (BVs) for the primary IEX region, while the secondary IEX continued up to 6528 BV. At the end of the operation, DOC and UVA254 removal in the effluent of the BIEX columns were 68% and 81%, respectively, compared to influent water. This was followed by 30% and 57% DOC and UVA254 removal using M4 (ceramic MF). The stabilised flux remained approximately 3.8-5.2 LMH both before and after the cleaning process, suggesting that membrane materials do not play a pivotal role. The mean stabilised flux of polymeric membranes increased after cleaning, whereas that of the ceramics decreased. Enhanced air-water backwash flow and pressure resulted in an increased removal of hydraulic reversible fouling, which was identified as the dominant fouling type. Ceramic membranes exhibited a higher removal of reversible hydraulic fouling than polymeric membranes. Chemical cleaning had a low impact on flux recovery; therefore, we recommend solely employing physical cleaning.

Fabrication and characterization of indium fluoride multimode fused fiber couplers for the mid-infrared.

Results of the fabrication and characterization of optical fiber couplers made of multimode step-index fluoroindate (InF3) fibers are presented. The fabrication setup was customized for this type of glass with a constant source of controlled nitrogen flow heated to a target temperature with an accuracy ±1°C. Combined with a novel fast fusion approach and with excellent control of the viscosity throughout the process, the clean gas flow and well-controlled temperature enable the fabrication of fused fiber couplers absent of any noticeable crystallization. A coupling ratio of 45/55 was achieved, with an excess loss of 0.35 dB, at 1.7 µm. To the best of our knowledge, this represents the first low excess loss (<1 dB), multimode, InF3 fiber couplers.

Speckle contrast reduction through the use of a modally-specific photonic lantern for optical coherence tomography.

A few-mode optical coherence tomography (FM-OCT) system was developed around a 2 × 1 modally-specific photonic lantern (MSPL) centered at 1310 nm. The MSPL allowed FM-OCT to acquire two coregistered images with uncorrelated speckle patterns generated by their specific coherent spread function. Here, we showed that averaging such images in vitro and in vivo reduced the speckle contrast by up to 28% and increased signal-to-noise ratio (SNR) by up to 48% with negligible impact on image spatial resolution. This method is compatible with other speckle reduction techniques to further improve OCT image quality.

Calibration procedure for enhanced mirror artifact removal in full-range optical coherence tomography using passive quadrature demultiplexing.

Significance: Passive quadrature demultiplexing allows full-range optical coherence tomography (FR-OCT). However, imperfections in the wavelength- and frequency-response of the demodulation circuits can cause residual mirror artifacts, which hinder high-quality imaging on both sides of zero delay. Aim: We aim at achieving high mirror artifact extinction by calibrated postprocessing of the FR-OCT signal. Approach: We propose a mathematical framework for the origin of the residual mirror peaks as well as a protocol allowing the precise measurement and correction of the associated errors directly from mirror measurements. Results: We demonstrate high extinction of the mirror artifact over the entire imaging range, as well as an assessment of the method's robustness to time and experimental conditions. We also provide a detailed description of the practical implementation of the method to ensure optimal reproducibility. Conclusion: The proposed method is simple to implement and produces high mirror artifact extinction. This may encourage the adoption of FR-OCT in clinical and industrial systems or loosen the performance requirements on the optical demodulation circuit, as the imperfections can be handled in postprocessing.

Viscosity of fluoride glass fibers for fused component fabrication.

Fluoride glasses show great promise for mid-IR fiber-based applications. Their brittleness and low glass transition temperature have thus far been obstacles towards obtaining low-loss fused components. Here, we suggest a simple method to measure glass viscosity over a range of process temperatures of interest for fused coupler fabrication. We achieved tapers of inverse taper ratio (ITR) 0.12 in multimode fluoroindate fibers. Tapers with loss <0.1dB at ITR 0.3 and no visible defects were fabricated with high repeatability. This work paves the way towards low-loss fused optical couplers in fluoride glass fiber.

Double-Clad Fiber-Based Multifunctional Biosensors and Multimodal Bioimaging Systems: Technology and Applications.

Optical fibers have been used to probe various tissue properties such as temperature, pH, absorption, and scattering. Combining different sensing and imaging modalities within a single fiber allows for increased sensitivity without compromising the compactness of an optical fiber probe. A double-clad fiber (DCF) can sustain concurrent propagation modes (single-mode, through its core, and multimode, through an inner cladding), making DCFs ideally suited for multimodal approaches. This study provides a technological review of how DCFs are used to combine multiple sensing functionalities and imaging modalities. Specifically, we discuss the working principles of DCF-based sensors and relevant instrumentation as well as fiber probe designs and functionalization schemes. Secondly, we review different applications using a DCF-based probe to perform multifunctional sensing and multimodal bioimaging.

All-fiber few-mode optical coherence tomography using a modally-specific photonic lantern.

Optical coherence tomography (OCT) was recently performed using a few-mode (FM) fiber to increase contrast or improve resolution using a sequential time-domain demultiplexing scheme isolating the different interferometric signals of the mode-coupled backscattered light. Here, we present an all-fiber FM-OCT system based on a parallel modal demultiplexing scheme exploiting a novel modally-specific photonic lantern (MSPL). The MSPL allows for maximal fringe visibility for each fiber propagation mode in an all-fiber assembly which provides the robustness required for clinical applications. The custom-built MSPL was designed for OCT at 930 nm and is wavelength-independent over the broad OCT spectrum. We further present a comprehensive coupling model for the interpretation of FM-OCT images using the first two propagation modes of a few-mode fiber, validate its predictions, and demonstrate the technique using in vitro microbead phantoms and ex vivo biological samples.

Morphometric and Microstructural Changes During Murine Retinal Development Characterized Using In Vivo Optical Coherence Tomography.

Purpose: The purpose of this study was to develop an in vivo optical coherence tomography (OCT) system capable of imaging the developing mouse retina and its associated morphometric and microstructural changes. Methods: Thirty-four wild-type mice (129S1/SvlmJ) were anesthetized and imaged between postnatal (P) day 7 and P21. OCT instrumentation was developed to optimize signal intensity and image quality. Semi-automatic segmentation tools were developed to quantify the retinal thickness of the nerve fiber layer (NFL), inner plexiform layer (IPL), inner nuclear layer (INL), and the outer retinal layers (ORL), in addition to the total retina. The retinal maturation was characterized by comparing layer thicknesses between consecutive time points. Results: From P7 to P10, the IPL increased significantly, consistent with retinal synaptogenesis. From P10 to P12, the IPL and ORL also increased, which is coherent with synaptic connectivity and photoreceptor maturation. In contrast, during these periods, the INL decreased significantly, consistent with cellular densification and selective apoptotic "pruning" of the tissue during nuclear migration. Thereafter from P12 to P21, the INL continued to thin (significantly from P17 to P21) whereas the other layers remained unchanged. No time-dependent changes were observed in the NFL. Overall, changes in the total retina were attributed to those in the IPL, INL, and ORL. Regions of the retina adjacent to the optic nerve head were thinner than distal regions during maturation. Conclusions: Changes in retinal layer thickness are consistent with retinal developmental mechanisms. Accordingly, this report opens new horizons in using our system in the mouse to characterize longitudinally developmental digressions in models of human diseases.

Real-time co-localized OCT surveillance of laser therapy using motion corrected speckle decorrelation.

We present a system capable of real-time delivery and monitoring of laser therapy by imaging with optical coherence tomography (OCT) through a double-clad fiber (DCF). A double-clad fiber coupler is used to inject and collect OCT light into the core of a DCF and inject the therapy light into its larger inner cladding, allowing for both imaging and therapy to be perfectly coregistered. Monitoring of treatment depth is achieved by calculating the speckle intensity decorrelation occurring during tissue coagulation. Furthermore, an analytical noise correction was used on the correlation to extend the maximum monitoring depth. We also present a method for correcting motion-induced decorrelation using a lookup table. Using the value of the noise- and motion-corrected correlation coefficient in a novel approach, our system is capable of identifying the depth of thermal coagulation in real time and automatically shut the therapy laser off when the targeted depth is reached. The process is demonstrated ex vivo in rat tongue and abdominal muscles for depths ranging from 500 µm to 1000 µm with induced motion in real time.

Coregistered optical coherence tomography and frequency-encoded multispectral imaging for spectrally sparse color imaging.

We present a system combining optical coherence tomography (OCT) and multispectral imaging (MSI) for coregistered structural imaging and surface color imaging. We first describe and numerically validate an optimization model to guide the selection of the MSI wavelengths and their relative intensities. We then demonstrate the integration of this model into an all-fiber bench-top system. We implement frequency-domain multiplexing for the MSI to enable concurrent acquisition of both OCT and MSI at OCT acquisition rates. Such a system could be implemented in endoscopic practices to provide multimodal, high-resolution imaging of deep organ structures that are currently inaccessible to standard video endoscopes.

Rapid head and neck tissue identification in thyroid and parathyroid surgery using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a noninvasive imaging modality that may reproduce the microarchitecture of tissues in real-time. This study examines whether OCT can render distinct images of thyroid, parathyroid glands, adipose tissue, and lymph nodes in both healthy and pathological states. METHODS: Twenty-seven patients undergoing thyroidectomy, parathyroidectomy, and/or neck dissection for thyroid cancer were recruited prospectively for imaging prior to histopathological analysis. RESULTS: Based on 122 imaged specimens, qualitative OCT descriptions were derived for healthy thyroid, parathyroid gland, adipose tissue, and lymph node. The frequencies at which distinguishing features were present for each tissue type were 88%, 83%, 100%, and 82%. OCT appearance of pathological specimens were also described. CONCLUSIONS: Healthy neck tissues have distinct OCT appearances, which could facilitate parathyroid identification during thyroidectomies. However, images of parathyroid adenomas could be confused with those of lymph nodes, and benign and malignant thyroid nodules could not be differentiated.

Simple and robust calibration procedure for k-linearization and dispersion compensation in optical coherence tomography.

In Fourier-domain optical coherence tomography (FD-OCT), proper signal sampling and dispersion compensation are essential steps to achieve optimal axial resolution. These calibration steps can be performed through numerical signal processing, but require calibration information about the system that may require lengthy and complex measurement protocols. We report a highly robust calibration procedure that can simultaneously determine correction vectors for nonlinear wavenumber sampling and dispersion compensation. The proposed method requires only two simple mirror measurements and no prior knowledge about the system's illumination source or detection scheme. This method applies to both spectral domain and swept-source OCT systems. Furthermore, it may be implemented as a low-cost fail-safe to validate the proper function of calibration hardware such as k-clocks. We demonstrate the method's simple implementation, effectiveness, and robustness on both types of OCT systems.

Utility of Optical Coherence Tomography for Guiding Laser Therapy Among Patients With Recurrent Respiratory Papillomatosis.

Importance: Recurrent respiratory papillomatosis (RRP) is a viral-induced disease caused by human papillomavirus and the second leading cause of dysphonia in children; however, neither a cure nor a definitive surgical treatment is currently available for RRP. Although laser therapy is often used in the treatment of RRP, the lack of real-time laser-tissue interaction feedback undermines the ability of physicians to provide treatments with low morbidity. Therefore, an intraoperative tool to monitor and control laser treatment depth is needed. Objective: To investigate the potential of combining optical coherence tomography (OCT) with laser therapy for patient-tailored laryngeal RRP treatments. Design, Setting, and Participants: This in vivo study was performed at the Massachusetts Eye and Ear Infirmary from February 1, 2017, to September 1, 2017. Three-dimensional OCT images were acquired before, during, and after photoangiolytic laser therapy in 10 pediatric patients with a history of papilloma growth who presented with lesions and hoarseness. Main Outcomes and Measures: Whether intraoperative OCT monitoring of changes in optical scattering and absorption provides quantitative information to control thermal damage in tissue. Results: Among the 10 pediatric patients (age range, 4-11 years; 6 male) included in the study, high-resolution OCT images revealed epithelial hyperplasia with clear RRP lesion margins. Images acquired during therapy indicated coagulation deep in tissue, and posttherapy images showed the ability to quantify the amount of tissue ablated by the photoangiolytic laser. Conclusions and Relevance: Concurrent use of OCT imaging and laser therapy may improve postoperative outcomes for patients with RRP by delivering an optimal, patient-tailored treatment. Additional studies investigating the correlation between optical properties with vocal outcomes are required.

Radiometric model for coaxial single- and multimode optical emission from double-clad fiber.

Double-clad fibers (DCFs) are versatile waveguides supporting a single-mode core surrounded by a multimode inner cladding. DCFs are increasingly used for multimodal biomedical applications, such as imaging or therapy, for which the core is typically used for coherent illumination and the inner cladding, to support a concurrent modality. Proper optimization is, however, critical to ensure high optical performance and requires accurate modeling of coaxial single- and multimode output beams. In this paper, we present an approach based on geometrical optics and radiometry, which provides a simple and efficient modeling tool for designing and optimizing DCF-based systems. A radiometric definition of single- and multimode output beams in terms of irradiance and radiant intensity allows for the modeling of the energy distribution along the beams' propagation. We confirmed the validity of the model through comparison with experimental measurements and demonstrate the use of the model for optimizing a catheter for concurrent OCT and laser coagulation.

Dimension reduction technique using a multilayered descriptor for high-precision classification of ovarian cancer tissue using optical coherence tomography: a feasibility study.

Optical coherence tomography (OCT) yields microscopic volumetric images representing tissue structures based on the contrast provided by elastic light scattering. Multipatient studies using OCT for detection of tissue abnormalities can lead to large datasets making quantitative and unbiased assessment of classification algorithms performance difficult without the availability of automated analytical schemes. We present a mathematical descriptor reducing the dimensionality of a classifier's input data, while preserving essential volumetric features from reconstructed three-dimensional optical volumes. This descriptor is used as the input of classification algorithms allowing a detailed exploration of the features space leading to optimal and reliable classification models based on support vector machine techniques. Using imaging dataset of paraffin-embedded tissue samples from 38 ovarian cancer patients, we report accuracies for cancer detection [Formula: see text] for binary classification between healthy fallopian tube and ovarian samples containing cancer cells. Furthermore, multiples classes of statistical models are presented demonstrating [Formula: see text] accuracy for the detection of high-grade serous, endometroid, and clear cells cancers. The classification approach reduces the computational complexity and needed resources to achieve highly accurate classification, making it possible to contemplate other applications, including intraoperative surgical guidance, as well as other depth sectioning techniques for fresh tissue imaging.

Morphologic three-dimensional scanning of fallopian tubes to assist ovarian cancer diagnosis.

The majority of high-grade serous ovarian cancers is now believed to originate in the fallopian tubes. Therefore, current practices include the pathological examination of excised fallopian tubes. Detection of tumors in the fallopian tubes using current clinical approaches remains difficult but is of critical importance to achieve accurate staging and diagnosis. Here, we present an intraoperative imaging system for the detection of human fallopian tube lesions. The system is based on optical coherence tomography (OCT) to access subepithelial tissue architecture. To demonstrate that OCT could identify lesions, we analyzed 180 OCT volumes taken from five different ovarian lesions and from healthy fallopian tubes, and compared them to standard pathological review. We demonstrated that qualitative features could be matched to pathological conditions. We then determined the feasibility of intraluminal imaging of intact human fallopian tubes by building a dedicated endoscopic single-fiber OCT probe to access the mucosal layer inside freshly excised specimens from five patients undergoing prophylactic surgeries. The probe insertion into the lumen acquired images over the entire length of the tubes without damaging the mucosa, providing the first OCT images of intact human fallopian tubes.

Simultaneous multimodal ophthalmic imaging using swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography.

Scanning laser ophthalmoscopy (SLO) benefits diagnostic imaging and therapeutic guidance by allowing for high-speed en face imaging of retinal structures. When combined with optical coherence tomography (OCT), SLO enables real-time aiming and retinal tracking and provides complementary information for post-acquisition volumetric co-registration, bulk motion compensation, and averaging. However, multimodality SLO-OCT systems generally require dedicated light sources, scanners, relay optics, detectors, and additional digitization and synchronization electronics, which increase system complexity. Here, we present a multimodal ophthalmic imaging system using swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (SS-SESLO-OCT) for in vivo human retinal imaging. SESLO reduces the complexity of en face imaging systems by multiplexing spatial positions as a function of wavelength. SESLO image quality benefited from single-mode illumination and multimode collection through a prototype double-clad fiber coupler, which optimized scattered light throughput and reduce speckle contrast while maintaining lateral resolution. Using a shared 1060 nm swept-source, shared scanner and imaging optics, and a shared dual-channel high-speed digitizer, we acquired inherently co-registered en face retinal images and OCT cross-sections simultaneously at 200 frames-per-second.

Combined optical coherence tomography and hyperspectral imaging using a double-clad fiber coupler.

This work demonstrates the combination of optical coherence tomography (OCT) and hyperspectral imaging (HSI) using a double-clad optical fiber coupler. The single-mode core of the fiber is used for OCT imaging, while the inner cladding of the double-clad fiber provides an efficient way to capture the reflectance spectrum of the sample. The combination of both methods enables three-dimensional acquisition of the sample morphology with OCT, enhanced with complementary molecular information contained in the hyperspectral image. The HSI data can be used to highlight the presence of specific molecules with characteristic absorption peaks or to produce true color images overlaid on the OCT volume for improved tissue identification by the clinician. Such a system could be implemented in a number of clinical endoscopic applications and could improve the current practice in tissue characterization, diagnosis, and surgical guidance.