Endoscopic Microscopy XX

Early detection of Barrett's Esophagus (BE) is essential for preventing esophageal adenocarcinoma. Recently, swallowable tethered capsule OCT endomicroscopy (OCT-TCE), a minimally invasive technique, has emerged as a promising alternative for BE screening, with clinical data demonstrating its efficacy. However, the current diagnostic approach involves manual analysis of extensive OCT image data, which is time-consuming, laborious, and subject to variability. To address this, we propose a deep learning (DL) model based on DenseNet for detecting BE from in-vivo OCT-TCE images. The DL framework was trained and validated on clinical data comprising 1,500 OCT-TCE images categorized into squamous, BE, and cardia. The DL model achieved an accuracy of 98.33%, with a precision, recall, and F1-score for BE detection of 0.9783, and a ROC-AUC of 0.99. This DL-based approach can reduce the complexity of OCT-TCE image analysis, making it more suitable for population-based screening.

Pulmonary hypertension (PH) and vascular remodeling are associated with the pathogenesis and progression of interstitial lung diseases (ILD) and other pulmonary diseases. Unfortunately, resolution limitations of CT imaging and invasiveness of right heart catheterization make assessment of vascular changes challenging. Endobronchial optical coherence tomography (EB-OCT) is a minimally-invasive, bronchoscope-compatible imaging technique that can visualize microscopic ILD features in the lung, including pulmonary arteries adjacent to the airway wall. Here, we demonstrate the feasibility of in vivo EB-OCT imaging combined with deep learning and artificial intelligence (AI) for robust, automated detection and segmentation of pulmonary arterial vessels in ILD patients.

Learning-based methods have shown their potential to improve the performance and real-time capability of non-uniform rotational distortion (NURD) correction in endoscopic optical coherence tomography (OCT). Currently, training a model for NURD correction requires massive endoscopic OCT data and the pseudo distortion vectors extracted from them. However, the availability of such data, the time consumption of pre-processing, and their pseudo nature limit the application of learning-based NURD correction. Here we propose novel supervision generation strategies to address the above issues. We verified the effectiveness of the above strategies on two publicly available endoscopic OCT datasets and the data collected from our home-built system, and on both CNN- and transformer-based architectures. Our methods are advantageous for implementing learning-based NURD correction in laboratory and data-limited settings, which may contribute to developing novel endoscopic imaging techniques and applications.

This study introduces a novel method leveraging computer-generated holography (CGH) to extend the depth of focus (DOF) in endoscopic Optical Coherence Tomography (OCT) with high uniformity and efficiency. By employing multi-level diffractive optics and CGH's multi-dimensional light-field modulation capabilities, precise control over the OCT probe light's intensity distribution is achieved. The method eliminates the need for an objective lens and enables direct fabrication at the distal end of a single-mode fiber using femtosecond laser two-photon 3D printing. The approach's superiority is confirmed through numerical simulation, beam measurement, and imaging results from a home-built endoscopic OCT system, offering significant potential for enhancing OCT imaging in clinical applications.

This manuscript discusses key aspects of confocal microendoscope lens design for multimodal imaging capability. It focuses on the design, modeling, and performance evaluation of a scanning fiber endoscope that is capable of optical coherence tomography (OCT) and fluorescence imaging (FI) that is restricted to 2mm outer diameter. To accurately model the input light beam from the scanning fiber, a study using Finite Element Analysis (FEA) was performed to study the scanning fiber movement, and the data was then used for optical design modeling.

Proximal scanning, with much lower manufacturing cost, causes severe beam stability issues (also known as non-uniform rotational distortion, NURD), which hinders the extension of its applications to functional imaging, such as OCT elastography (OCE). In this work, we demonstrate the abilities of learning-based NURD correction methods to enable the imaging stability required for intensity-based proximal-scanning endoscopic OCE. Using the air pressure of a balloon catheter as a mechanical stimulus, our proximal-scanning endoscopic OCE could effectively differentiate between areas of varying stiffness of atherosclerotic vascular phantoms. Compared with the existing endoscopic OCE methods that can measure only in the radial direction, our method first achieves 2D BM-mode displacement/strain distribution in both radial and circumferential directions. We think it is promising for many clinical applications such as on-site diagnosis, intraoperative monitoring, and therapeutic evaluation.

The metalens has attracted significant attention due to its lightweight and ultrathin planar structure, showcasing capabilities that surpass traditional bulky refractive optics. This paper proposes a dual-wavelength metalens with a diameter of 650 μm, operating at 780 nm and 830 nm, designed to integrate with a coherent fiber bundle for a confocal laser endomicroscopy system. This system achieves cellular-level resolution and high fluorescence contrast, significantly reducing the imaging probe's size without compromising performance. The metalens enables clear visualization of microscopic structures in the mice colon mucosal layer, demonstrating its potential for clinical applications in diagnosing gastrointestinal diseases.

Metasurfaces possess vast potential for flexible beam shaping with reduced physical footprint compared to traditional refractive bulk optics. Such devices, in general, are a rapidly growing field with high potential for allowing functional improvements over conventional optical coherence tomography catheter designs such as ball lenses or GRIN-based lenses, in addition to enhancing image quality. Previously our group demonstrated the integration of a metalens into a fully functioning OCT catheter. Here we present the continuation of that work, discussing refinements in design and the successful fabrication of the metalens directly onto a 0.5 mm prism. This work represents an important step in achieving the goal of ultra-compact metalens-based optical imaging catheters.

We developed a compact scattering-based light sheet microscope probe for human tissue imaging. A custom miniature objective lens was designed for the compact sLSM probe to achieve an NA of 0.22 with ±1 mm FOV. The dimensions of the probe were 4 cm x 4 cm x 10 cm. The probe achieved an axial resolution of 5.6 μm and a lateral resolution of 1.9 μm. Preliminary images of fixed human tissues showed the compact sLSM probe could visualize cellular details of fixed human anal epithelial tissues in a similar manner to a bench sLSM device using off-the-shelf objective lenses.

The effectiveness of endoscopic optical coherence tomography (OCT) relies on the ability to access internal organs and resolve lesions, necessitating a high-resolution miniature OCT endoscope. The 800-nm OCT offers higher axial resolution and enhanced image contrast compared to 1,300-nm OCT but faces fabrication challenges. Traditional methods result in suboptimal surface roughness and unwanted scattering, degrading image quality. We introduce a two-photon polymerization (TPP) 3D glass printing method to fabricate high-performance ultrathin OCT endoscopes. This method creates highly customized microlenses with smooth surfaces, superior transmission, and enhanced thermal stability. The glass microlenses have a low surface roughness of about 5 nm, with minimal deviations from designed profile. The 0.6 mm diameter endoscopes achieve high imaging performance with ultrahigh resolution of 2.4 μm axial × 7.2 μm transverse and over 90% one-way transmission. We demonstrate excellent image quality and translational potential through in vivo imaging of the mouse aorta and deep brain.

We present a flexible side-firing helically scanning multiphoton endoscope for imaging small diameter ductal tissues. The endoscope incorporates 0.5mm optics within a 1.0mm diameter outer sheath. The optical system consists of a dual clad fiber encased within a torque coil attached to a high numerical aperture 3D printed objective lens system. Multiphoton signal is generated using 1400 nm femtosecond pulsed light delivered via the fiber core, with the emitted signal collected via the first cladding. The objective lens features a custom fold prism with an aspheric surface on its exit face, and an additional biconic surface to compensate for the sheath induced aberration. Prototyping of this system began with a simpler low numerical aperture system to optimize design, printing parameters, and assembly techniques. We modelled lens system performance in Zemax OpticStudio and experimentally evaluated their performance both with and without the outer sheath present.

Our lab has developed a transnasal imaging system based on optical coherence tomography (OCT) for non-invasive, safe imaging of the upper gastrointestinal tract in pregnant women. This system offers a low-cost, rapid, and safe alternative to traditional endoscopy, especially in situations where sedation or invasive procedures are contraindicated. In this study, 36 women from Mass General Hospital (MGH) and Aga Khan University (AKU), including both pregnant and non-pregnant participants, underwent transnasal OCT imaging. The results demonstrated successful imaging in 97% of cases, with no complications. This technology could provide a valuable tool for diagnosing gastrointestinal conditions such as Environmental Enteric Disease (EED) in vulnerable populations, including pregnant women.

OCT in combination with Near Infrared Fluorescence imaging, where targeted monoclonal antibodies are labelled with a dye fluorescing in the near infrared, provides micron-resolution structural information, and co-localised molecular information. Endoscopic Immuno-OCT is a minimally invasive, targeted and high-resolution imaging technique for the imaging of tissue epithelia. We present in vivo data for patients intravenously injected with fluorescently labeled Bevacizumab (anti-VEGF) prior to imaging with an in house developed capsule endoscope. The capsule endoscope, with an outer diameter of 12 mm, is fitted with a double clad fiber for dual-modality imaging, and has an approximate axial and lateral resolution of 7 and 30 micron respectively. To the date of submission, 2 Barrett’s esophagus patients, requiring a tissue resection procedure, have successfully undergone in vivo imaging using the capsule, and initial results demonstrate good in vivo OCT imaging quality and fluorescence sensitivity for the tracer.

Fibrotic interstitial lung diseases (fILDs) are heterogeneous group of disorders characterized by abnormal collagen deposition with progressive fibrosis, worsening lung function and poor prognosis. We previously evaluated the capability of polarization-sensitive endobronchial optical coherence tomography (PS-EB-OCT), a bronchoscope-compatible polarimetric imaging modality, for in-vivo microscopic visualization of birefringent fibrosis in fILDs. Here, we further investigate depth-resolved optic-axis (OA) orientation mapping to assess localized fibrotic collagen orientation in fILDs in-vivo. PS-EB-OCT was conducted 80 pullback imaging sites from 15 fILD subjects undergoing surgical lung biopsy for clinical diagnosis. OA-mapped PS-EB-OCT provided in-vivo volumetric visualization of microscopic collagen orientation in normal parenchyma, non-specific interstitial pneumonia, and usual interstitial pneumonia in fILD patients, which matched expected histopathologic features and provided an ability to separate disease progression outcomes obtained from clinical follow-up.

Currently, no diagnostic method exists to visualize and measure the airway smooth muscle (ASM) in vivo. Endoscopic Polarization Sensitive Optical Coherence Tomography (PS-OCT) enables ASM detection and quantification, by assessing tissue birefringence. We performed in vivo PS-OCT in patients with interstitial lung diseases (n=14), asthma (n=1) and healthy volunteers (n=2). The airways were circumferentially scanned at 52fps Bscan rate using an in-house built distal scanning catheter (1.35 mm). Preliminary results show an increased ASM median percentage in diseased airways compared to healthy. We demonstrated PS-OCT to be a minimally invasive technique to assess ASM thickness in both diseased and healthy airways.

The goal of bronchial thermoplasty (BT) is to reduce the symptoms associated with asthma by ablating the hyper-responsive airway smooth (ASM), but results have been mixed. In this work we present the results of a study in which we imaged human patients before and one year following BT using polarization-sensitive optical coherence tomography (PS-OCT) in order to assess the potential of PS-OCT for use in conjunction with the BT procedure. Metrics were assessed using a fully-automated segmentation approach, and included epithelial and mucosal thickness, as well as ASM thickness and tension.

High-resolution, in vivo assessment of lung biomechanical properties has the potential to provide novel insight into the pathogenesis and therapeutic targeting of fibrotic interstitial lung diseases (fILD), including idiopathic pulmonary fibrosis (IPF). We have previously demonstrated that endobronchial optical coherence tomography (EB-OCT) can provide minimally-invasive in vivo diagnosis of fILD in patients with high sensitivity and specificity, compared to independently evaluated histopathology and clinical diagnosis. In this study, we investigate the application of EB-OCT elastography to measure the microscopic mechanical properties of normal and fibrotic lung parenchymal tissue in tissue mimicking phantoms and in vivo human subjects with fILD.

This study explores the use of a self-developed endoscopic system integrated with near-infrared indocyanine green (ICG) fluorescence imaging for the diagnosis and treatment of polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSCR). By leveraging this advanced endoscopic technology, the method effectively penetrates subretinal hemorrhages to accurately locate polyps and bleeding points. This innovative approach significantly enhances the precision of therapeutic interventions such as photodynamic therapy and laser photocoagulation, offering promising advancements in the minimally invasive management of retinal and choroidal disorders.

A lightweight wireless mesoscope achieves large-scale neural imaging in unconstrained mice performing freely behaviors, supporting neurobehavioral research during complex social interactions and environmental exploration.

A complete endomicroscopy system allowing fast, three-dimensional, in-vivo optical coherence tomography (OCT) within the urinary bladder is presented. This portable imaging system, approved by national authorities, ensures safety for both patients and operators, while enabling seamless incorporation to the clinical routine in surgical theaters. By providing non-invasive, cross-sectional, and three-dimensional image data, we anticipate an improved detection rate for early-stage and flat lesions. Within an in-vivo pilot study, the developed OCT system is deployed within the General Hospital of Vienna. Our system's capabilities enhance the assessment of bladder tumors, promising improved accuracy and diagnostic potential.

Blue-light excitation (450 nm) autofluorescence imaging (AFI) has demonstrated utility for label-free cancer detection through visualization of collagen restructuring associated with pathologic advancement. However, endoscopic applications are limited by poor signal-to-background ratio (SBR). We characterize component fluorescence contributions and demonstrate an optical coherence tomography and AFI endoscopic system optimized for visualization of low-signal endogenous fluorophores. A novel all-silica imaging catheter is compared against two existing devices, through measuring AFI SBR in water and 0.98 µM fluorescein. The resulting system demonstrates 50X improvement in AFI SBR compared to our existing OCT-AFI methods.

The angular distribution of light backscattered from tissue varies with carcinogenesis, owing in part to changes in the shape, size and optical density of epithelial nuclei. Few-mode fiber (FMF) optical coherence tomography (OCT) potentially offers insight into these changes through angular-sensitive imaging. This work explores the creation of the first endoscopic FMF OCT system with the goal of developing a device for early cancer detection. Using a free-space coupling joint, we demonstrate implementation of FMF OCT in a fiber-coupled OCT system. Endoscopic imaging of tissue is enabled using a micromotor catheter.

We demonstrate an all-reflective tethered capsule endoscope (RTCE) utilizing double-clad fiber and reflective optics for achromatic multimodal imaging of the esophagus. This device uses a custom ellipsoidal mirror to focus the light from the fiber tip onto the sample. In this work, we first describe key design parameters and highlight important assembly steps. We then demonstrate several data processing/analysis methods for signal multiplexing, rotation stabilization, and image analysis. Finally, we demonstrate the implementation of the capsule by performing combined OCT and spectral imaging in ex-vivo biological samples.

In this work, we discuss the challenges encountered and lessons learned while assembling a submillimeter, multi-channeled, multi-modality endoscope for falloposcopic use. These difficulties include the by-hand alignment and adhesion of the micro-optic components, as well as the physical integration of the imaging system with flexible, opaque endoscope bodies of different polymer types. With thorough experimentation, we were able to address these, and other, assembly challenges while developing Standard Operating Procedures to ensure consistent endoscopic construction between assemblers. We hope that through sharing this information, others will be able to sidestep the challenges we have found during our assembly process, and therefore accelerate the research being done on microendoscopic work.

We present the development of a fiber-optic RS-OCT probe for 785 nm Raman system and 1310 nm OCT system. The probe has compact and symmetric design allowing for colocalized RS acquisition and OCT imaging with diameter of 3.4 mm and rigid length of ~30 mm, allowing for tissue screening by simultaneous chemical composition and structural imaging through the working channels of colonoscopes.