Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.
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Rajadhyaksha, M., Gonzalez, S., Zavislan, J.M., Anderson, R.R. & Webb, R.H. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J. Invest. Dermatol. 113, 293–303 (1999).
Kiesslich, R. et al. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 127, 706–713 (2004).
Huang, D. et al. Optical coherence tomography. Science 254, 1178–1181 (1991).
Tearney, G.J. et al. Optical biopsy in human gastrointestinal tissue using optical coherence tomography. Am. J. Gastroenterol. 92, 1800–1804 (1997).
Poneros, J.M. et al. Diagnosis of specialized intestinal metaplasia by optical coherence tomography. Gastroenterology 120, 7–12 (2001).
Pfau, P.M. et al. Criteria for the diagnosis of dysplasia by endoscopic optical coherence tomography. Gastrointest. Endosc. 58, 196–202 (2003).
Yabushita, H. et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation 106, 1640–1645 (2002).
Kingsley, S.A. & Davies, D.E.N. OFDR diagnostics or fibre and integrated-optic systems. Electron. Lett. 21, 434–435 (1985).
Fercher, A.F., Hitzenberger, C.K., Kamp, G. & El-Zaiat, S.Y. Measurement of intraocular distances by backscattering spectral interferometry. Opt. Commun. 117, 43–45 (1995).
Leitgeb, R., Hitzenberger, C.K. & Fercher, A.F. Performance of Fourier domain vs. time domain optical coherence tomography. Opt. Express 11, 889–894 (2003).
de Boer, J.F. et al. Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography. Opt. Lett. 28, 2067–2069 (2003).
Choma, M.A., Sarunic, M.V., Changhuei, Y. & Izatt, J.A. Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Opt. Express 11, 2183–2189 (2003).
Yun, S.H., Tearney, G.J., de Boer, J.F., Iftimia, N. & Bouma, B.E. High-speed optical frequency-domain imaging. Opt. Express 11, 2953–2963 (2003).
Bouma, B.E., Tearney, G.J., Compton, C.C. & Nishioka, N.S. High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography. Gastrointest. Endosc. 51, 467–474 (2000).
Kobayashi, K., Izatt, J.A., Kulkarni, M.D., Willis, J. & Sivak, M.V. High-resolution cross-sectional imaging of the gastrointestinal tract using optical coherence tomography: preliminary results. Gastrointest. Endosc. 47, 515–523 (1998).
Jang, I.K. et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J. Am. Coll. Cardiol. 39, 604–609 (2002).
Jang, I.K. et al. In vivo characterization of coronary atherosclerotic plaque using optical coherence tomography. Circulation 111, 1551–1555 (2005).
Bouma, B.E. et al. Evaluation of intracoronary stenting by intravascular optical coherence tomography. Heart 89, 317–321 (2003).
Evans, J.A. et al. Optical coherence tomography to identify intramucosal carcinoma and high-grade dysplasia in Barrett's esophagus. Clin. Gastroenterol. Hepatol. 4, 38–43 (2006).
Libby, P. Inflammation in atherosclerosis. Nature 420, 868–874 (2002).
Davies, M.J. Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture. Circulation 94, 2013–2020 (1996).
Virmani, R., Kolodgie, F.D., Burke, A.P., Farb, A. & Schwartz, S.M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).
MacNeill, B.D. et al. Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease. J. Am. Coll. Cardiol. 44, 972–979 (2004).
Tearney, G.J. et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 107, 113–119 (2003).
Boppart, S.A., Oldenburg, A.L., Xu, C.Y. & Marks, D.L. Optical probes and techniques for molecular contrast enhancement in coherence imaging. J. Biomed. Opt. 10, 41208 (2005).
Yang, C., Choma, M.A., Lamb, L.E. & Simon, J.D. Protein-based molecular contrast optical coherence tomography with phytochrome as the contrast agent. Opt. Lett. 29, 1396–1398 (2004).
Vakoc, B.J., Yun, S.H., de Boer, J.F., Tearney, G.J. & Bouma, B.E. Phase-resolved optical frequency domain imaging. Opt. Express 13, 5483–5493 (2005).
Zhang, J., Jung, W., Nelson, J.S. & Chen, Z. Full range polarization-sensitive Fourier domain optical coherence tomography. Opt. Express 12, 6033–6039 (2004).
Yun, S.H., Boudoux, C., Tearney, G.J. & Bouma, B.E. High-speed wavelength-swept semiconductor laser with polygon-scanner-based wavelength filter. Opt. Lett. 28, 1981–1983 (2003).
This research was supported in part by the US National Institutes of Health (contracts R01 HL070039, R33 CA110130, R01 RR0119768, R01 HL076398 and R01 CA103769) and by the Terumo Corporation.
The authors have pending patent applications relating to the imaging technology described in this manuscript. A portion of the research described in this manuscript was provided by the Terumo Corporation through a sponsored research agreement with Massachusetts General Hospital.
Optical frequency domain imaging system schematic. (PDF 221 kb)
OFDI movie of swine esophagus acquired in vivo. The x-axis corresponds to the azimuthal angle of the catheter from 0 to 2π, and the y-axis represents the radial coordinate (depth). To reduce the file size, the longitudinal segment length was limited to 3.7 mm, the individual images were downsampled and significant image compression was applied. The influence of the beating of the heart at a period of 1.4 s is seen. (MOV 1374 kb)
OFDI movie acquired during a pull-back of ∼2 cm in a swine coronary artery in vivo. The movie consists of 432 frames, significantly compressed from the original, which were acquired in 4 sec but displayed at a 3-fold decreased frame rate with an inverse grayscale lookup table. (AVI 2054 kb)
OFDI movie acquired in a human coronary artery in vitro. Although the anatomy of the human coronary arteries is similar to that of swine, minimum pathology will typically be present in the form of intimal hyperplasia as observed throughout this vessel. (AVI 1165 kb)
OFDI movie of beating Xenopus embryo heart. Full volume images were acquired (50 ms each) during beating of the embryo heart. At end diastole, the ventricle was dilated to its greatest volume whereas the volumes of the atrium and truncus were at their minima. In systole, it compresses and the truncus arteriosus expands and rotates. (AVI 2449 kb)
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Yun, S., Tearney, G., Vakoc, B. et al. Comprehensive volumetric optical microscopy in vivo. Nat Med 12, 1429–1433 (2006). https://doi.org/10.1038/nm1450
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