We have previously demonstrated a miniaturized transnasal introduction tube (TNIT) for transnasal endomicroscopy (TNEM) with optical coherence tomography (OCT) for clinical imaging of the small intestine of infants and adults in vivo. Although the TNIT is a convenient and effective way to implement TNEM, OCT probes for imaging through the TNIT had long manufacturing times and low yields, and its multiple cylindrical surfaces caused severe optical aberrations, degrading OCT image quality. Here we introduce a new optical design for 3D-printed microoptics that correct TNIT-induced astigmatism. Preliminary results show that the lens improves resolution and can be reliably manufactured.

To address the unmet need to study the microstructure changes in the cochlea that occur with sensorineural hearing loss, we have constructed a miniature flexible micro-OCT catheter that can be inserted into the human cochlea and acquire images with cellular-level resolution. The OCT catheter was designed, fabricated, and characterized. Crucial mechanical properties (flexibility, insertion force) were measured and found to be comparable to those of commercial cochlear implants. These early results suggest that this new device may provide a viable approach for diagnosing SNHL and selecting the most appropriate treatments on an individual patient basis.

We present a miniaturized handheld OCT probe (9 grams weight), approximately the size of a small pen (10 mm x 140 mm), developed for use inside a patient’s mouth for examination of the oral mucosa. The probe operates in common-path mode and uses a magnetic scanning system to actuate a lensed fibre, achieving 50 B-scans per second. The system is demonstrated with OCT imaging of the buccal and alveolar mucosa of six patients with oral lichen planus (OLP) during clinical routine examination, and showed pathological changes in the tissue microarchitecture.

A component used to extend the depth of field for compact endoscopic OCT probes is the mirror tunnel. BeamLab software, which uses the beam propagation method, was used to simulate the mirror tunnel probes and quantify depth of field extension and lateral resolution. Considering the exit face of the mirror tunnel as an extended object decouples the physical operation of the mirror tunnel from the focusing optics, which reduces the optimization parameter space. Lateral resolution performance was found to depend heavily on the metric chosen, with strong side lobes reducing image contrast; hence, the optimization merit function should be carefully chosen.

We present a flexible, compact, 2photon, 3photon, SHG and CARS nonlinear endo-microscope featuring a 2.2 mm outer diameter and a length of 34 mm. It uses a negative curvature hollow-core double-clad fiber that is scanned with a resonant piezo-scanner. The fiber design allows distortion-less, background-free delivery of femtosecond and picosecond excitation pulses and the back-collection of nonlinear signals through the same fiber. Sub-micron spatial resolution together with >300 microns field of view is made possible using micro-lenses or GRIN based miniature objective lens. We demonstrate 2-photon and 3-photon fluorescence, SHG, THG and CARS imaging at a rate of 10 frames/s.

Fluorophores associated with early development of cancer (FAD, NADH, collagen) and abnormalities in microvessel structure have been shown to correlate with oral cancer progression. Co-registered imaging approaches using optical coherence tomography (OCT) and fluorescence imaging techniques have demonstrated promise in assessing these biomarkers, but current endoscopic approaches are limited in specificity. We propose that a micromotor-based OCT angiography and fluorescence-lifetime imaging microscopy (FLIM) may provide a suitable biopsy guidance tool for oral cancer screening. We present initial work towards implementing these modalities with a micromotor catheter system, validated with phantoms. Performance is compared to our existing OCT-autofluorescence system.

This work presents the design and implementation of an endoscopic probe for point-of-care diagnosis of bladder cancer, with an outer diameter of 4.5 mm that allows for in-vivo usage. This triple-modality device can deliver volumetric OCT images, optoacoustic tomograms, and single point Raman spectroscopy that target complementary biomarkers. The probe features a piezo-based fiber scanner, which delivers the illumination or excitation light for all modalities, with a maximum Field of View of 1.6 mm. The same path is used for light collection for OCT imaging. A separate fiber is used for detection of the Raman signals, while two additional fibers with microcavity tips sense the ultrasonic waves for optoacoustic tomography. A hyperchromatic micro-optical objective provides a working distance optimized for each modality. The probe housing is produced by selective laser-induced etching of fused silica.

Side-viewing catheter-based medical imaging modalities are used to produce cross-sectional images underneath tissue surfaces. Mainstream side-viewing catheters are based on Optical Coherence Tomography (OCT) or Ultrasound, and they are often applied to the luminal environment. Automatic lumen segmentation provides geometry information for tasks like robotic control and lumen assessment for real-time diagnosis task with side-viewing catheters. In this work, we propose a novel lumen segmentation deep neural networks based on explicit coordinates encoding, which is named CE-net. CE-net is computationally efficient and produces and produces clean segmentation by explicitly encoding the boundaries coordinates in one shot. The experimental evaluation shows a processing time of approximately 8ms per frame while maintaining robustness. We propose a data generation method to improve CE-net generalization, which shows considerable performance by just training with a small dataset.

Coherent Fiber Bundels (CFB) enable ultrathin lensless endoscopes, but suffer from phase distortions. Currently spatial light modulators are used for phase conjugation enabling 3D imaging, without distal optics. We introduce diffractive optical elements (DOE) for aberration correction. DOEs made by 2-photon lithography are used to correct static phase distortions and enable direct transfer of holograms for 3D imaging. Furthermore, random DOEs can code 3D object information in 2D intensity speckle patterns, which are decoded using neural networks. Both approaches enable single shot 3D imaging, in a compact and robust system with diameters below 500 µm for deep brain imaging.

There is a critical need for a technology that can assist doctors in more accurately evaluating lung nodules at the time of biopsy. To address this need, a multispectral fluorescence line-scan confocal microendoscope was developed that employs a fiber bundle to image tissue at the distal tip of the biopsy needle. The multispectral nature of the instrument allows the simultaneous use of multiple FDA-approved dyes that stain different cellular/tissue compartments in different spectral regions to distinguish between lung cancer and benign lesions of the lung. The imaging system has been used to image ex vivo mouse and human lung tissue.

A fiber-optic probe with a low numerical aperture lens at its tip is better suited for imaging the large airways, as the distance between the probe and the tissue surface is unknown and variable. A multi-segment, all-fiber lens, that consists of a section of coreless fiber (CF) and graded index fiber, followed by a CF ball lens section is described. With this design, lenses with a working distance (WD) greater than 7 mm can be obtained with ball diameters as small as 365 µm and nearly collimated beams with WD greater than 14 mm are demonstrated with a ~500 µm ball tip.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal type of interstitial lung disease (ILD) characterized by abnormal fibrotic scarring of lung parenchyma. We have demonstrated the use of endobronchial optical coherence tomography (EB-OCT) as a minimally-invasive approach for in vivo diagnosis of ILD in patients with high sensitivity and specificity. Here, we investigate the feasibility of EB-OCT elastography to measure the microscopic mechanical properties of normal and fibrotic lung parenchymal tissue in ex vivo porcine lung and in vivo in human subjects with ILD.

In this work, we demonstrate the ability to image and quantify airway changes, we were able to quantify a decrease in airway compliance. The proposed approach will enable further investigations of using OCT assessing pulmonary injury to prevent/treat ARDS using a chlorine inhalation injury model, as well as diagnosing of large airway injury and compliance change due to airway toxic chemical exposure. With enhanced portability over conventional bronchoscopy, we believe our system is capable of field hospital deployment and investigating airway conditions in warfighters. Combining OCT and pressure transducer with bronchoscopy would enhance assessment and treatment of large airway chemical injury.

Idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease (ILD), characterized by abnormal collagen deposition. Computed tomography imaging lacks the resolution to accurately distinguish and quantify fibrosis distribution at the microscopic level, and surgical biopsy methods are invasive. We demonstrate the feasibility of polarization sensitive endobronchial optical coherence tomography (PS EB-OCT) for quantitative in vivo microscopic assessment of fibrotic ILDs. PS EB-OCT was able to accurately distinguish fibrosis distribution patterns in IPF and non-IPF ILDs, independently compared against surgical biopsy. These findings support the potential of PS EB-OCT as a minimally-invasive method for assessment of ILD.

Endoscopic biopsies play a vital role in the diagnosis of many diseases of the gastrointestinal (GI) tract. The standard means of biopsy capture using forceps presents challenges in obtaining adequate tissue samples, especially for unsedated transnasal endoscopy (uTNE). Cryobiopsy is an emerging minimally-invasive alternative where the distal tip of a dual-lumen uTNE probe is cooled momentarily, freezing and adhering the tissue in contact, which is collected for histology. OCT image guidance during cryobiopsy can enable pre-biopsy lesion examination; however, dimensional constraints make this challenging. Here, we demonstrate a microscale 3D-printed device capable of minimally-invasive side-viewing OCT image-guided cryobiopsy though uTNE scopes.

Eosiophilic esophagitis (EoE) is an inflammatory disease of the esophagus, with long-term EoE causing fibrotic and hypertrophic restructuring of the sub-epithelial wall. We have developed a polarization-sensitive micro-optical coherence tomography (PS-µOCT) imaging device for its characterization. This device was used to quantify collagen at 15 sites on each of 5 swine esophagi, with results compared to histology. A linear mixed model with random intercept showed significant agreement between OCT and histology (slope = 0.41, 95% CI [0.22, 0.60], t(67) = 4.30, p = 5.8 x 10-5). This validates our technology and will allow longitudinal assessment of patient response to drug and diet, without endoscopic biopsy.

Optical Coherence Tomography (OCT) shows the ability of real-time diagnosis for the external environment or internal small lumen. OCT has not been applied to larger internal lumen like the colon or stomach due to the difficulty of scanning. In this work, we use a robotized helical scanning probe to explore large lumen. Based on the segmentation of the stabilized OCT image, high accurate distance and quantitative contact feedback are obtained for the robotic scanning. The proposed method for distance/contact feedback shows robustness on both phantom and real deformable colon tissue. The robotic scanning is conducted on the soft phantom.

A scanning fiber endoscope system utilizing an alternative collection method for improved collection efficiency is presented. Low probability of two-photon excitation and high tissue scattering make signal collection a challenging aspect of two-photon imaging. Our work demonstrates a collection strategy using a high NA optical fiber bundle utilized in addition to the excitation fiber. This scheme significantly increases collection area without requiring collection optics at distal end. Experimentally determined collection efficiency of the method will be compared against our table-top two-photon microscope setup. Various effects of increased collection area on efficiency will be discussed with simulation results.

Tethered capsule endomicroscopy (TCE) is a recently developed form of in vivo microscopy based on optical coherence tomography (OCT). With TCE, a small tethered pill is swallowed, procuring high resolution microscopic images of the esophageal wall. TCE does not require sedation and is thus a more rapid and convenient procedure comparing to traditional endoscopic examination. Our group and others have successfully conducted OCT-TCE in pilot, single-center studies that demonstrated the potential of this technology for upper GI tract diagnosis. Here, we demonstrate and evaluate the feasibility and safety of a next generation OCT-TCE system and device in patients with Barrett’s esophagus (BE) and report the initial longitudinal analysis of the natural history of BE.

We developed OCT-TCE devices with either guidewire or propylene glycol infusion tethers and tested pullback force and tissue damage over different distances of the small intestine in living swine. For all devices, the maximum force was below our safety threshold of 2N across intestinal lengths of 4m or less. At lengths > 4m, the force was > 4N for the infusion tube devices and > 5N for the guidewire devices, and the proximal intestine showed visible damage matching the tether shape. In conclusion, TCE may be safe for jejunal imaging but likely needs further improvement for ileum imaging in humans.

We have developed an axially spectrally-encoded confocal endomicroscope that can visualize multiple depths of the tissue in a single image frame. We developed a custom hyperchromatic objective lens (focal length = 4.8 mm; NA = 0.68) to focus different wavelengths from a broadband light source into different axial depths of the tissue. The confocal endomicroscope achieved lateral and axial resolution of 2 μm and 4 μm, respectively over a lateral field of 468 μm and an axial depth range of 100 μm. The material cost was < $1500. Preliminary confocal images of human tissues in vivo clearly visualized cellular details.