Here, we introduce “tethered capsule endomicroscopy,” that involves swallowing an optomechanically-engineered pill that captures cross-sectional, 30 μm (lateral) × 7 μm (axial) resolution, microscopic images of the gut wall as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.

Abstract:We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo.

Owing to its superior resolution, intravascular optical coherence tomography (IVOCT) is a promising tool for imaging the microstructure of coronary artery walls. However, IVOCT does not identify chemicals and molecules in the tissue, which is required for a more complete understanding and accurate diagnosis of coronary disease. Here we present a dual-modality imaging system and catheter that uniquely combines IVOCT with diffuse near-infrared spectroscopy (NIRS) in a single dualmodality imaging device for simultaneous acquisition of microstructural and compositional information. As a proof-of-concept demonstration, the device has been used to visualize co-incident microstructural and spectroscopic information obtained from a diseased cadaver human coronary artery. Swanson, "Optical biopsy and imaging using optical coherence tomography," Nat. Med. 1(9), 970-972 (1995). 3. J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 1361-1367 (2003). 4. R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, "Performance of Fourier domain vs. time domain optical coherence tomography," Opt. Express 11(8), 889-894 (2003). 5. K. Goda, A. Fard, O. Malik, G. Fu, A. Quach, and B. Jalali, "High-throughput optical coherence tomography at 800 nm," Opt. Express 20(18), 19612-19617 (2012 A. Bartlett, M. Rosenberg, and B. E. Bouma, "Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging," JACC Cardiovasc. Imaging 1(6), 752-761 (2008). 10. S. Waxman, M. I. Freilich, M. J. Suter, M. Shishkov, S. Bilazarian, R. Virmani, B. E. Bouma, and G. J. Tearney, "A case of lipid core plaque progression and rupture at the edge of a coronary stent: elucidating the mechanisms of drug-eluting stent failure," Circ. Cardiovasc. Interv. 3(2), 193-196 (2010 Opt. Soc. Am. A 4(3), 423-432 (1987 21(11),