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:In this paper, we review the current state of technology development and clinical applications of endoscopic optical coherence tomography (OCT). Key design and engineering considerations are discussed for most OCT endoscopes, including side-viewing and forwardviewing probes, along with different scanning mechanisms (proximal-scanning versus distalscanning). Multi-modal endoscopes that integrate OCT with other imaging modalities are also discussed. The review of clinical applications of endoscopic OCT focuses heavily on diagnosis of diseases and guidance of interventions. Representative applications in several organ systems are presented, such as in the cardiovascular, digestive, respiratory, and reproductive systems. A brief outlook of the field of endoscopic OCT is also discussed. References and links 1. T. Cao and H. L. Tey, "High-definition optical coherence tomography -an aid to clinical practice and research in dermatology," J. Dtsch. Dermatol. Ges. 13(9), 886-890 (2015). 2. J. Olsen, L. Themstrup, and G. B. Jemec, "Optical coherence tomography in dermatology," G. Ital. Dermatol.Venereol. 150(5), 603-615 (2015). 3. M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R.Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, "Dynamic Optical Coherence Tomography in Dermatology," Dermatology (Basel) 232(3), 298-311 (2016). 4. G. J. Tearney, S. A. Boppart, B. E. Bouma, M. E. Brezinski, N. J. Weissman, J. F. Southern, and J. G. Fujimoto, "Scanning single-mode fiber optic catheter-endoscope for optical coherence tomography," Opt. Lett. 21(7), 543-545 (1996). 5. A. M. Rollins, R. Ung-Arunyawee, A. Chak, R. C. K. Wong, K. Kobayashi, M. V. Sivak, Jr., and J. A. Izatt, "Real-time in vivo imaging of human gastrointestinal ultrastructure by use of endoscopic optical coherence tomography with a novel efficient interferometer design," Opt. Lett. 24(19), 1358-1360 (1999). 6. M. V. Sivak, Jr., K. Kobayashi, J. A. Izatt, A. M. Rollins, R. Ung-Runyawee, A. Chak, R. C. Wong, G. A.Isenberg, and J. Willis, "High-resolution endoscopic imaging of the GI tract using optical coherence tomography," Gastrointest. Endosc. 51(4), 474-479 (2000). 7. J. Xi, A. Zhang, Z. Liu, W. Liang, L. Y. Lin, S. Yu, and X. Li, "Diffractive catheter for ultrahigh-resolution spectral-domain volumetric OCT imaging," Opt. Lett. 39(7), 2016-2019 (2014). 8. P. H. Tran, D. S. Mukai, M. Brenner, and Z. Chen, "In vivo endoscopic optical coherence tomography by use of a rotational microelectromechanical system probe," Opt. Lett. 29(11), 1236-1238 (2004). Goodnow, and C. Petersen, "Micromotor endoscope catheter for in vivo, ultrahigh-resolution optical coherence tomography," Opt. Lett. 29(19), 2261-2263 (2004). 10. T.-H. Tsai, B. Potsaid, Y. K. Tao, V. Jayaraman, J. Jiang, P. J. S. Heim, M. F. Kraus, C. Zhou, J. Hornegger, H.Mashimo, A. E. Cable, and J. G. Fujimoto, "Ultrahigh speed endoscopic optical coherence tomography using micromotor imaging catheter and VCSEL technology," Biomed. Opt. Express 4(7), 1119-11...

Abstract:We describe a new ultrahigh speed Spectral OCT instrument making use of a CMOS camera and demonstrate high quality in vivo imaging of the anterior segment of the human eye. The high flexibility of the designed imaging system allows a wide range of imaging protocols. Two-and three-dimensional high quality OCT images of the cornea, the anterior chamber and the crystalline lens are presented. A high acquisition rate, up to 135,000 A-scans/second enables three-dimensional reconstruction of the anterior segment during lenticular accommodation, blinking and pupillary reaction to light stimulus. We demonstrate OCT tomographic real time imaging of the lens dynamics during accommodation and high quality OCT cross-sectional images of the entire anterior segment of the eye from the cornea up to posterior part of the crystalline lens. 2009 Optical Society of America

We present an application of in vivo anterior segment imaging of the human eye with an ultrahigh speed swept source OCT instrument. For this purpose, a dedicated OCT system was designed and constructed. This instrument enables axial zooming by automatic reconfiguration of spectral sweep range; an enhanced imaging range mode enables imaging of the entire anterior segment while a high axial resolution mode provides detailed morphological information of the chamber angle and the cornea. The speed of 200,000 lines/s enables high sampling density in three-dimensional imaging of the entire cornea in 250 ms promising future applications of OCT for optical corneal topography, pachymetry and elevation maps. The results of a preliminary quantitative corneal analysis based on OCT data free form motion artifacts are presented. Additionally, a volumetric and real time reconstruction of dynamic processes, like pupillary reaction to light stimulus or blink-induced contact lens movements are demonstrated.

Background Biopsy surveillance protocols for the assessment of Barrett’s esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. Objective The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. Design A pilot feasibility study. Setting Massachusetts General Hospital. Patients A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett’s esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. Intervention Volumetric laser endomicroscopy. Main Outcome Measurements Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. Results There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%–83%), for VLE intent-to-biopsy images 93% (95% CI, 78%–99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. Limitations This is a single-center feasibility study with a limited number of patients. Conclusion Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. (Clinical trial registration number: NCT01439633.)

We present the applicability of high-speed swept source (SS) optical coherence tomography (OCT) for quantitative evaluation of the corneal topography. A high-speed OCT device of 108,000 lines/s permits dense 3D imaging of the anterior segment within a time period of less than one fourth of second, minimizing the influence of motion artifacts on final images and topographic analysis. The swept laser performance was specially adapted to meet imaging depth requirements. For the first time to our knowledge the results of a quantitative corneal analysis based on SS OCT for clinical pathologies such as keratoconus, a cornea with superficial postinfectious scar, and a cornea 5 months after penetrating keratoplasty are presented. Additionally, a comparison with widely used commercial systems, a Placido-based topographer and a Scheimpflug imaging-based topographer, is demonstrated.

Custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT) provided with automatic quantification and distortion correction algorithms was used to characterize three-dimensionally (3-D) the human crystalline lens in vivo in four subjects, for accommodative demands between 0 to 6 D in 1 D steps. Biol. Cybern. 54(3), 189-194 (1986a). 11. C. Miege and P. Denieul, "Mean response and oscillations of accommodation for various stimulus vergences in relation to accommodation feedback control," Ophthalmic Physiol. Opt. 8(2), 165-171 (1988). 12. L. F. Garner and M. K. Yap, "Changes in ocular dimensions and refraction with accommodation," Ophthalmic Physiol. Opt. 17(1), 12-17 (1997). 13. P. Rosales, M. Dubbelman, S. Marcos, and R. van der Heijde, "Crystalline lens radii of curvature from Purkinje and Scheimpflug imaging," J. Vis. 6(10), 1057-1067 (2006), http://www.journalofvision.org/6/10/5. 14. N. Brown, "The change in shape and internal form of the lens of the eye on accommodation," Exp. Eye Res.15 ( Ohbayashi, and K. Shimizu, "Full-range imaging of eye accommodation by high-speed long-depth range optical frequency domain imaging," Biomed.

Optical coherence tomography (OCT) is an optical diagnostic modality that can acquire cross-sectional images of the microscopic structure of the esophagus, including Barrett's esophagus (BE) and associated dysplasia. We developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires high-resolution images of entire gastrointestinal (GI) tract luminal organs. This device has a potential to become a screening method that identifies patients with an abnormal esophagus that should be further referred for upper endoscopy. Currently, the characterization of the OCT-TCE esophageal wall data set is performed manually, which is time-consuming and inefficient. Additionally, since the capsule optics optimally focus light approximately 500 µm outside the capsule wall and the best quality images are obtained when the tissue is in full contact with the capsule, it is crucial to provide feedback for the operator about tissue contact during the imaging procedure. In this study, we developed a fully automated algorithm for the segmentation of in vivo OCT-TCE data sets and characterization of the esophageal wall. The algorithm provides a two-dimensional representation of both the contact map from the data collected in human clinical studies as well as a tissue map depicting areas of BE with or without dysplasia. Results suggest that these techniques can potentially improve the current TCE data acquisition procedure and provide an efficient characterization of the diseased esophageal wall. prospective trial comparing unsedated esophagoscopy via transnasal and transoral routes using a 4-mm video endoscope with conventional endoscopy with sedation," Endoscopy 37(6), 559-565 (2005).