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Dual-modality optical coherence tomography and fluorescence tethered capsule endomicroscopy

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Abstract

OCT tethered capsule endomicroscopy (TCE) is an emerging noninvasive diagnostic imaging technology for gastrointestinal (GI) tract disorders. OCT measures tissue reflectivity that provides morphologic image contrast, and thus is incapable of ascertaining molecular information that can be useful for improving diagnostic accuracy. Here, we introduce an extension to OCT TCE that includes a fluorescence (FL) imaging channel for attaining complementary, co-registered molecular contrast. We present the development of an OCT-FL TCE capsule and a portable, plug-and-play OCT-FL imaging system. The technology is validated in phantom experiments and feasibility is demonstrated in a methylene blue (MB)-stained swine esophageal injury model, ex vivo and in vivo.

© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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Figures (6)

Fig. 1.
Fig. 1. Schematic diagram of OCT-FL TCE imaging system. (a) OCT imaging system, (b) FL imaging system, (c) OCT-FL TCE device. TLS – tunable light source, BS – fiber-optic beam splitter (50/50), CIR – fiber-optic circulator, L – lens, TS – linear translation stage, M – mirror, PBS – polarizing fiber-optic beam splitter, BD – balanced photo detector, DAQ – data acquisition board, MPU – motor power unit, PC – personal computer, CPU – central processing unit, SMF – single-mode fiber, PMF – polarization-maintaining fiber, DCF – double-clad fiber, MMF – multi-mode fiber, EL – electrical connection, FL-LS – fluorescence light source, SHU – fiber-optic shutter, PM – power meter, WDM – wavelength division multiplexer, DCFC – double-clad fiber coupler, EF – emission filter, PMT – photomultiplier tube.
Fig. 2.
Fig. 2. OCT-FL TCE imaging system and device. (a) Photo of the OCT-FL TCE imaging system comprising the OCT imaging system, the FL imaging system, and the OCT-FL TCE device. (b) Schematic diagram of capsule. (c) Photo of 2 m long OCT-FL TCE device composed of electrical and optical connections, tether, and capsule. (d) Magnified view of (c) showing capsule incorporating focusing optics (ball lens), side-directing mirror surface (reflective prism), and micro motor. Scale bars: 5 mm.
Fig. 3.
Fig. 3. OCT-FL TCE data display of representative images from swine esophagus, in vivo. (a) Polar and (b) Cartesian representation of the same cross-sectional scan, depicting 2D grayscale OCT and 1D false color FL data. (c) 3D representation of the cross-sectional OCT map along the axial extension of the esophagus (inverted grayscale: low-to-high as black-to-white). (d) 3D representation of the FL surface map along the axial extension of the esophagus. Scale bars: 1 mm.
Fig. 4.
Fig. 4. Results of the methylene blue (MB) fluorescence performance evaluation experiments. (a) PMT readout plotted as a function of MB solution concentration (error bars indicate ±1 standard deviation). (b) PMT readout plotted as a function of distance between the outer surface of the capsule imaging window and the capillary (error bars indicate ±1 standard deviation). (c) Representative Cartesian OCT-FL image from the concentration experiment. (d) Representative polar OCT-FL image from the attenuation experiment.
Fig. 5.
Fig. 5. Representative imaging results from the ex vivo esophagus study. (a) Photograph of a cut open esophageal tissue section for ground truth validation of the biopsy induced injury sites. (b) FL surface map and (c) OCT en face projection map (depth-averaged over entire imaging depth) of the same esophageal section. White arrow heads in (a)-(c) indicate matching injury sites in all three images. (d) Composite image overlaying (b) and (c), showing perfect co-registration. (e)-(h) Representative magnified views of the injury site indicated by the white square in (a)-(d) (OCT en face map here is depth-averaged over the first 300 μm of tissue from the epithelial surface). (i)-(k) Representative polar OCT cross-sections (including FL signal on top) of ROIs indicated in (b) and (c). Black arrow heads in (i)-(k) indicate matching injury sites between en face and cross-sectional images. Scale bars (a)-(d): 5 mm; (e)-(k): 1 mm.
Fig. 6.
Fig. 6. Representative imaging results from the in vivo swine esophageal imaging study. (a) Photograph of a cut open esophageal tissue section for ground truth validation of the biopsy induced injury sites. (b) FL background surface map, (c) FL MB surface map, and (d) OCT en face projection map (depth-averaged over entire imaging depth) of the same esophageal section. White arrow heads in (a), (c), and (d) indicate matching injury sites in all three images. (e), (f) Video endoscopy footage showing an injury site before and after MB staining procedure. (g) Video endoscopy footage showing TCE procedure at an MB-stained injury site. (h), (i) Representative magnified views of the injury site indicated by the white square in (c) and (d) (OCT en face map here is depth-averaged over the first 300 μm of tissue from the epithelial surface). This same injury site is also indicated by a white square in (e) and (f). (j) Composite image overlaying (h) and (i). (k)-(m) Representative polar OCT cross-sections (including FL signal on top) of ROIs indicated in (c) and (d). Black arrow heads in (k)-(m) indicate matching injury sites between en face and cross-sectional images. Scale bars (a)-(d): 5 mm; (h)-(m): 1 mm.
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