Metasurface-based bijective illumination collection imaging provides high-resolution tomography in three dimensions.

Microscopic imaging in three dimensions enables numerous biological and clinical applications. However, high-resolution optical imaging preserved in a relatively large depth range is hampered by the rapid spread of tightly confined light due to diffraction. Here, we show that a particular disposition of light illumination and collection paths liberates optical imaging from the restrictions imposed by diffraction. This arrangement, realized by metasurfaces, decouples lateral resolution from depth-of-focus by establishing a one-to-one correspondence (bijection) along a focal line between the incident and collected light. Implementing this approach in optical coherence tomography, we demonstrate tissue imaging at 1.3 µm wavelength with ~ 3.2 µm lateral resolution, maintained nearly intact over 1.25 mm depth-of-focus, with no additional acquisition or computation burden. This method, termed bijective illumination collection imaging, is general and might be adapted across various existing imaging modalities.

Correction of motion artifacts in endoscopic optical coherence tomography and autofluorescence images based on azimuthal en face image registration.

We present a method for the correction of motion artifacts present in two- and three-dimensional in vivo endoscopic images produced by rotary-pullback catheters. This method can correct for cardiac/breathing-based motion artifacts and catheter-based motion artifacts such as nonuniform rotational distortion (NURD). This method assumes that en face tissue imaging contains slowly varying structures that are roughly parallel to the pullback axis. The method reduces motion artifacts using a dynamic time warping solution through a cost matrix that measures similarities between adjacent frames in en face images. We optimize and demonstrate the suitability of this method using a real and simulated NURD phantom and in vivo endoscopic pulmonary optical coherence tomography and autofluorescence images. Qualitative and quantitative evaluations of the method show an enhancement of the image quality.

Nano-optic endoscope for high-resolution optical coherence tomography in vivo.

Acquisition of high-resolution images from within internal organs using endoscopic optical imaging has numerous clinical applications. However, difficulties associated with optical aberrations and the trade-off between transverse resolution and depth-of-focus significantly limit the scope of applications. Here, we integrate a metalens, with the ability to modify the phase of incident light at sub-wavelength level, into the design of an endoscopic optical coherence tomography catheter (termed nano-optic endoscope) to achieve near diffraction-limited imaging through negating non-chromatic aberrations. Remarkably, the tailored chromatic dispersion of the metalens in the context of spectral interferometry is utilized to maintain high-resolution imaging beyond the input field Rayleigh range, easing the trade-off between transverse resolution and depth-of-focus. We demonstrate endoscopic imaging both in resected human lung specimens and in sheep airways in vivo. The combination of the superior resolution and higher imaging depth-of-focus of the nano-optic endoscope will likely increase the clinical utility of endoscopic optical imaging.

Automated segmentation and quantification of airway mucus with endobronchial optical coherence tomography.

We propose a novel suite of algorithms for automatically segmenting the airway lumen and mucus in endobronchial optical coherence tomography (OCT) data sets, as well as a novel approach for quantifying the contents of the mucus. Mucus and lumen were segmented using a robust, multi-stage algorithm that requires only minimal input regarding sheath geometry. The algorithm performance was highly accurate in a wide range of airway and noise conditions. Mucus was classified using mean backscattering intensity and grey level co-occurrence matrix (GLCM) statistics. We evaluated our techniques in vivo in asthmatic and non-asthmatic volunteers.

Endoscopic high-resolution autofluorescence imaging and OCT of pulmonary vascular networks.

High-resolution imaging from within airways may allow new methods for studying lung disease. In this work, we report an endoscopic imaging system capable of high-resolution autofluorescence imaging (AFI) and optical coherence tomography (OCT) in peripheral airways using a 0.9 mm diameter double-clad fiber (DCF) catheter. In this system, AFI excitation light is coupled into the core of the DCF, enabling tightly focused excitation light while maintaining efficient collection of autofluorescence emission through the large diameter inner cladding of the DCF. We demonstrate the ability of this imaging system to visualize pulmonary vasculature as small as 12 µm in vivo.

Endoscopic Doppler optical coherence tomography and autofluorescence imaging of peripheral pulmonary nodules and vasculature.

We present the first endoscopic Doppler optical coherence tomography and co-registered autofluorescence imaging (DOCT-AFI) of peripheral pulmonary nodules and vascular networks in vivo using a small 0.9 mm diameter catheter. Using exemplary images from volumetric data sets collected from 31 patients during flexible bronchoscopy, we demonstrate how DOCT and AFI offer complementary information that may increase the ability to locate and characterize pulmonary nodules. AFI offers a sensitive visual presentation for the rapid identification of suspicious airway sites, while co-registered OCT provides detailed structural information to assess the airway morphology. We demonstrate the ability of AFI to visualize vascular networks in vivo and validate this finding using Doppler and structural OCT. Given the advantages of higher resolution, smaller probe size, and ability to visualize vasculature, DOCT-AFI has the potential to increase diagnostic accuracy and minimize bleeding to guide biopsy of pulmonary nodules compared to radial endobronchial ultrasound, the current standard of care.

Optical coherence tomography and autofluorescence imaging of human tonsil.

For the first time, we present co-registered autofluorescence imaging and optical coherence tomography (AF/OCT) of excised human palatine tonsils to evaluate the capabilities of OCT to visualize tonsil tissue components. Despite limited penetration depth, OCT can provide detailed structural information about tonsil tissue with much higher resolution than that of computed tomography, magnetic resonance imaging, and Ultrasound. Different tonsil tissue components such as epithelium, dense connective tissue, lymphoid nodules, and crypts can be visualized by OCT. The co-registered AF imaging can provide matching biochemical information. AF/OCT scans may provide a non-invasive tool for detecting tonsillar cancers and for studying the natural history of their development.

A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography.

We present a power-efficient fiber-based imaging system capable of co-registered autofluorescence imaging and optical coherence tomography (AF/OCT). The system employs a custom fiber optic rotary joint (FORJ) with an embedded dichroic mirror to efficiently combine the OCT and AF pathways. This three-port wavelength multiplexing FORJ setup has a throughput of more than 83% for collected AF emission, significantly more efficient compared to previously reported fiber-based methods. A custom 900 µm diameter catheter ‒ consisting of a rotating lens assembly, double-clad fiber (DCF), and torque cable in a stationary plastic tube ‒ was fabricated to allow AF/OCT imaging of small airways in vivo. We demonstrate the performance of this system ex vivo in resected porcine airway specimens and in vivo in human on fingers, in the oral cavity, and in peripheral airways.

Fiber-optic polarization diversity detection for rotary probe optical coherence tomography.

We report a polarization diversity detection scheme for optical coherence tomography with a new, custom, miniaturized fiber coupler with single mode (SM) fiber inputs and polarization maintaining (PM) fiber outputs. The SM fiber inputs obviate matching the optical lengths of the X and Y OCT polarization channels prior to interference and the PM fiber outputs ensure defined X and Y axes after interference. Advantages for this scheme include easier alignment, lower cost, and easier miniaturization compared to designs with free-space bulk optical components. We demonstrate the utility of the detection system to mitigate the effects of rapidly changing polarization states when imaging with rotating fiber optic probes in Intralipid suspension and during in vivo imaging of human airways.

Coregistered autofluorescence-optical coherence tomography imaging of human lung sections.

Autofluorescence (AF) imaging can provide valuable information about the structural and metabolic state of tissue that can be useful for elucidating physiological and pathological processes. Optical coherence tomography (OCT) provides high resolution detailed information about tissue morphology. We present coregistered AF-OCT imaging of human lung sections. Adjacent hematoxylin and eosin stained histological sections are used to identify tissue structures observed in the OCT images. Segmentation of these structures in the OCT images allowed determination of relative AF intensities of human lung components. Since the AF imaging was performed on tissue sections perpendicular to the airway axis, the results show the AF signal originating from the airway wall components free from the effects of scattering and absorption by overlying layers as is the case during endoscopic imaging. Cartilage and dense connective tissue (DCT) are found to be the dominant fluorescing components with the average cartilage AF intensity about four times greater than that of DCT. The epithelium, lamina propria, and loose connective tissue near basement membrane generate an order of magnitude smaller AF signal than the cartilage fluorescence.

Multimodal tissue imaging: using coregistered optical tomography data to estimate tissue autofluorescence intensity change due to scattering and absorption by neoplastic epithelial cells.

Autofluorescence (AF) imaging provides valuable information about the structural and chemical states of tissue that can be used for early cancer detection. Optical scattering and absorption of excitation and emission light by the epithelium can significantly affect observed tissue AF intensity. Determining the effect of epithelial attenuation on the AF intensity could lead to a more accurate interpretation of AF intensity. We propose to use optical coherence tomography coregistered with AF imaging to characterize the AF attenuation due to the epithelium. We present imaging results from three vital tissue models, each consisting of a three-dimensional tissue culture grown from one of three epithelial cell lines (HCT116, OVCAR8, and MCF7) and immobilized on a fluorescence substrate. The AF loss profiles in the tissue layer show two different regimes, each approximately linearly decreasing with thickness. For thin cell cultures (<300 µm), the AF signal changes as AF(t)/AF(0)=1-1.3t (t is the thickness in millimeter). For thick cell cultures (>400 µm), the AF loss profiles have different intercepts but similar slopes. The data presented here can be used to estimate AF loss due to a change in the epithelial layer thickness and potentially to reduce AF bronchoscopy false positives due to inflammation and non-neoplastic epithelial thickening.

Nanoplasmonic terahertz photoconductive switch on GaAs.

Low-temperature (LT) grown GaAs has a subpicosecond carrier response time that makes it favorable for terahertz photoconductive (PC) switching. However, this is obtained at the price of lower mobility and lower thermal conductivity than GaAs. Here we demonstrate subpicosecond carrier sweep-out and over an order of magnitude higher sensitivity in detection from a GaAs-based PC switch by using a nanoplasmonic structure. As compared to a conventional GaAs PC switch, we observe 40 times the peak-to-peak response from the nanoplasmonic structure on GaAs. The response is double that of a commercial, antireflection coated LT-GaAs PC switch.

Single-walled carbon nanotubes as base material for THz photoconductive switching: a theoretical study from input power to output THz emission.

This paper studies the relation between photoexcitation of a single-walled carbon nanotube (SWNT) based device, and its THz output power in the context of THz photoconductive (PC) switching and THz photomixing. A detailed approach of calculating output THz power for such a device describes the effect of each parameter on the performance of the THz PC switch and highlights the design dependent achievable limits. A numerical assessment, with typical values for each parameter, shows that-subject to thermal stability of the device-SWNT based PC switch can improve the output power by almost two orders of magnitudes compared to conventional materials such as LT-GaAs.

Efficient terahertz slot-line waveguides.

We present two solutions to the challenge of radiation loss of slot-lines at terahertz frequencies: using a slot-line in a homogeneous medium, and using a slot-line on a layered substrate. A theoretical analysis of the slot-line in a homogeneous medium as a terahertz transmission line is presented. The absorption coefficient is obtained in terms of the waveguide dimensions using the field distribution of the slot-line. Results show that the slot-line in a homogeneous medium and the slot-line on a layered substrate can be effective transmission lines for terahertz waves with 2 cm(-1) and 3 cm(-1) absorption due to conductor loss. Full-wave numerical simulations using the Finite Element Method (FEM) are applied to validate the theory.

Coupling of terahertz waves to a two-wire waveguide.

We calculate theoretically the coupling of a terahertz wave from a dipole into a two-wire waveguide. The field transmission and reflection are obtained using a Single Mode Matching (SMM) technique at the input port of the two-wire waveguide. The results show more than 70 percent coupling efficiency for the waveguide using 500 µm radii wires with 2mm center-to-center separation and the exciting field cross section of 1mm × 1mm. The results also show good agreement with the full-wave numerical simulations using the Finite Element Method (FEM).

Two-wire waveguide for terahertz.

We present a rigorous theoretical analysis of the two-wire waveguide. Obtaining the attenuation constant in terms of the dimensions of the waveguide analytically, we show that the absorption coefficient can be less than 0.01 cm(-1), with the appropriate values of the dimensions.