Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Three-dimensional endomicroscopy using optical coherence tomography

Nature Photonics volume 1, pages 709–716 (2007)Cite this article

Abstract

Optical coherence tomography enables micrometre-scale, subsurface imaging of biological tissue by measuring the magnitude and echo time delay of backscattered light. Endoscopic optical coherence tomography imaging inside the body can be performed using fibre-optic probes. To perform three-dimensional optical coherence tomography endomicroscopy with ultrahigh volumetric resolution, however, requires extremely high imaging speeds. Here we report advances in optical coherence tomography technology using a Fourier-domain mode-locked frequency-swept laser as the light source. The laser, with a 160-nm tuning range at a wavelength of 1,315 nm, can produce images with axial resolutions of 5–7 µm. In vivo three-dimensional optical coherence tomography endomicroscopy is demonstrated at speeds of 100,000 axial lines per second and 50 frames per second. This enables virtual manipulation of tissue geometry, speckle reduction, synthesis of en face views similar to endoscopic images, generation of cross-sectional images with arbitrary orientation, and quantitative measurements of morphology. This technology can be scaled to even higher speeds and will open up three-dimensional optical-coherence-tomography endomicroscopy to a wide range of medical applications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: FDML laser schematic and performance.
Figure 2: 3D-OCT set-up.
Figure 3: Volumetric renderings of in vivo rabbit colon.
Figure 4: Longitudinal (YZ) images through the centre of the colon volume.
Figure 5: En face (XY ) images from colonic mucosa layer.
Figure 6: Cross-sectional (XZ ) images with quantitative feature measurements.

Similar content being viewed by others

References

  1. Huang, D. et al. Optical coherence tomography. Science 254, 1178–1181 (1991).

    Article  ADS  Google Scholar 

  2. Tearney, G. J. et al. In vivo endoscopic optical biopsy with optical coherence tomography. Science 276, 2037–2039 (1997).

    Article  Google Scholar 

  3. Herz, P. R. et al. Ultrahigh resolution optical biopsy with endoscopic optical coherence tomography. Opt. Express 12, 3532–3542 (2004).

    Article  ADS  Google Scholar 

  4. Tumlinson, A. R. et al. In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope. J. Biomed. Opt. 11, 06092RR (2006).

  5. Swanson, E. A. et al. In vivo retinal imaging by optical coherence tomography. Opt. Lett. 18, 1864–1866 (1993).

    Article  ADS  Google Scholar 

  6. Tearney, G. J., Bouma, B. E. & Fujimoto, J. G. High-speed phase- and group-delay scanning with a grating-based phase control delay line. Opt. Lett. 22, 1811–1813 (1997).

    Article  ADS  Google Scholar 

  7. Rollins, A. M., Kulkarni, M. D., Yazdanfar, S., Ung-arunyawee, R. & Izatt, J. A. In vivo video rate optical coherence tomography. Opt. Express 3, 219–229 (1998).

    Article  ADS  Google Scholar 

  8. Hsiung, P.-L. et al. High-speed path-length scanning with a multiple-pass cavity delay line. Appl. Opt. 42, 640–648 (2003).

    Article  ADS  Google Scholar 

  9. Yang, V. X. D. et al. High speed, wide velocity dynamic range Doppler optical coherence tomography (Part I): System design, signal processing, and performance. Opt. Express 11, 794–809 (2003).

    Article  ADS  Google Scholar 

  10. Oldenburg, A. L., Reynolds, J. J., Marks, D. L. & Boppart, S. A. Fast-Fourier-domain delay line for in vivo optical coherence tomography with a polygonal scanner. Appl. Opt. 42, 4606–4611 (2003).

    Article  ADS  Google Scholar 

  11. Barfuss, H. & Brinkmeyer, E. Modified optical frequency-domain reflectometry with high spatial-resolution for components of integrated optic systems. J. Lightwave Technol. 7, 3–10 (1989).

    Article  ADS  Google Scholar 

  12. Glombitza, U. & Brinkmeyer, E. Coherent frequency-domain reflectometry for characterization of single-mode integrated-optical wave-guides. J. Lightwave Technol. 11, 1377–1384 (1993).

    Article  ADS  Google Scholar 

  13. Passy, R., Gisin, N., Vonderweid, J. P. & Gilgen, H. H. Experimental and theoretical investigations of coherent OFDR with semiconductor-laser sources. J. Lightwave Technol. 12, 1622–1630 (1994).

    Article  ADS  Google Scholar 

  14. Vonderweid, J. P., Passy, R. & Gisin, N. Midrange coherent optical frequency-domain reflectometry with a DFB laser-diode coupled to an external cavity. J. Lightwave Technol. 13, 954–960 (1995).

    Article  ADS  Google Scholar 

  15. Passy, R., Gisin, N. & Vonderweid, J. P. High-sensitivity-coherent optical frequency-domain reflectometry for characterization of fiberoptic network components. IEEE Photon. Technol. Lett. 7, 667–669 (1995).

    Article  ADS  Google Scholar 

  16. Fercher, A. F., Hitzenberger, C. K., Kamp, G. & Elzaiat, S. Y. Measurement of intraocular distances by backscattering spectral interferometry. Opt. Commun. 117, 43–48 (1995).

    Article  ADS  Google Scholar 

  17. Chinn, S. R., Swanson, E. A. & Fujimoto, J. G. Optical coherence tomography using a frequency-tunable optical source. Opt. Lett. 22, 340–342 (1997).

    Article  ADS  Google Scholar 

  18. Golubovic, B., Bouma, B. E., Tearney, G. J. & Fujimoto, J. G. Optical frequency-domain reflectometry using rapid wavelength tuning of a Cr4+:forsterite laser. Opt. Lett. 22, 1704–1706 (1997).

    Article  ADS  Google Scholar 

  19. Choma, M. A., Sarunic, M. V., Yang, C. H. & Izatt, J. A. Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Opt. Express 11, 2183–2189 (2003).

    Article  ADS  Google Scholar 

  20. 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).

    Article  ADS  Google Scholar 

  21. Leitgeb, R., Hitzenberger, C. K. & Fercher, A. F. Performance of Fourier domain vs. time domain optical coherence tomography. Opt. Express 11, 889–894 (2003).

    Article  ADS  Google Scholar 

  22. 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).

    Article  ADS  Google Scholar 

  23. Oh, W. Y., Yun, S. H., Vakoc, B. J., Tearney, G. J. & Bouma, B. E. Ultrahigh-speed optical frequency domain imaging and application to laser ablation monitoring. Appl. Phys. Lett. 88, 103902 (2006).

    Article  ADS  Google Scholar 

  24. Yun, S. H. et al. Comprehensive volumetric optical microscopy in vivo. Nature Med. 12, 1429–1433 (2006).

    Article  Google Scholar 

  25. Vakoc, B. J. et al. Comprehensive esophageal microscopy by using optical frequency-domain imaging. Gastrointestinal Endoscopy 65, 898–905 (2007).

    Article  Google Scholar 

  26. Huber, R., Wojtkowski, M., Taira, K., Fujimoto, J. G. & Hsu, K. Amplified, frequency swept lasers for frequency domain reflectometry and OCT imaging: design and scaling principles. Opt. Express 13, 3513–3528 (2005).

    Article  ADS  Google Scholar 

  27. Huber, R., Wojtkowski, M. & Fujimoto, J. G. Fourier domain mode locking (FDML): A new laser operating regime and applications for optical coherence tomography. Opt. Express 14, 3225–3237 (2006).

    Article  ADS  Google Scholar 

  28. Huber, R., Adler, D. C. & Fujimoto, J. G. Buffered Fourier domain mode locking (FDML): Unidirectional swept laser sources for OCT imaging at 370,000 lines per second. Opt. Lett. 31, 2975–2977 (2006).

    Article  ADS  Google Scholar 

  29. Adler, D. C., Huber, R. & Fujimoto, J. G. Phase-sensitive optical coherence tomography at up to 370,000 lines per second using buffered Fourier domain mode locked lasers. Opt. Lett. 32, 626–628 (2007).

    Article  ADS  Google Scholar 

  30. Wojtkowski, M., Kowalczyk, A., Leitgeb, R. & Fercher, A. F. Full range complex spectral optical coherence tomography technique in eye imaging. Opt. Lett. 27, 1415–1417 (2002).

    Article  ADS  Google Scholar 

  31. Choma, M. A., Yang, C. H. & Izatt, J. A. Instantaneous quadrature low-coherence interferometry with 3 × 3 fiber-optic couplers. Opt. Lett. 28, 2162–2164 (2003).

    Article  ADS  Google Scholar 

  32. Davis, A. M., Choma, M. A. & Izatt, J. A. Heterodyne swept-source optical coherence tomography for complete complex conjugate ambiguity removal. J. Biomed. Opt. 10, 064005 (2005).

    Article  ADS  Google Scholar 

  33. Yun, S. H., Tearney, G. J., de Boer, J. F. & Bouma, B. E. Removing the depth-degeneracy in optical frequency domain imaging with frequency shifting. Opt. Express 12, 4822–4828 (2004).

    Article  ADS  Google Scholar 

  34. Zhang, J., Nelson, J. S. & Chen, Z. P. Removal of a mirror image and enhancement of the signal-to-noise ratio in Fourier-domain optical coherence tomography using an electro-optic phase modulator. Opt. Lett. 30, 147–149 (2005).

    Article  ADS  Google Scholar 

  35. Brinkmeyer, E. & Ulrich, R. High-resolution OCDR in dispersive wave-guides. Electron. Lett. 26, 413–414 (1990).

    Article  Google Scholar 

  36. Wojtkowski, M., Leitgeb, R., Kowalczyk, A., Bajraszewski, T. & Fercher, A. F. In vivo human retinal imaging by Fourier domain optical coherence tomography. J. Biomed. Opt. 7, 457–463 (2002).

    Article  ADS  Google Scholar 

  37. Takayama, T. et al. Aberrant crypt foci of the colon as precursors of adenoma and cancer. New Engl. J. Med. 339, 1277–1284 (1998).

    Article  Google Scholar 

  38. Hsiung, P. L. et al. Ultrahigh-resolution and 3-dimensional optical coherence tomography ex vivo imaging of the large and small intestines. Gastrointestinal Endoscopy 62, 561–574 (2005).

    Article  Google Scholar 

  39. Tumlinson, A. R. et al. Endoscope-tip interferometer for ultrahigh resolution frequency domain optical coherence tomography in mouse colon. Opt. Express 14, 1878–1887 (2006).

    Article  ADS  Google Scholar 

  40. Li, H. et al. Feasibility of interstitial Doppler optical coherence tomography for in vivo detection of microvascular changes during photodynamic therapy. Lasers Surg. Med. 38, 754–761 (2006).

    Article  Google Scholar 

  41. Aalders, M. C. G. et al. Doppler optical coherence tomography to monitor the effect of photodynamic therapy on tissue morphology and perfusion. J. Biomed. Opt. 11, 044011 (2006).

    Article  ADS  Google Scholar 

  42. Hanna, N. M. et al. Feasibility of three-dimensional optical coherence tomography and optical Doppler tomography of malignancy in hamster cheek pouches. Photomed. Laser Surg. 24, 402–409 (2006).

    Article  Google Scholar 

  43. Seki, J., Satomura, Y., Ooi, Y., Yanagida, T. & Seiyama, A. Velocity profiles in the rat cerebral microvessels measured by optical coherence tomography. Clin. Hemorheol. Microcirc. 34, 233–239 (2006).

    Google Scholar 

Download references

Acknowledgements

We gratefully thank Bob Shearer from Lightlabs Imaging for his contributions. This research was sponsored by the National Institutes of Health (grants R01-CA75289-09 and R01-EY011289-20), Air Force Office of Scientific Research (grants FA9550-040-1-0046 and FA9550-040-1-0011), National Science Foundation (grants BES-0522845 and ECS-0501478), the Natural Sciences and Engineering Research Council of Canada (supporting D.C.A.), and the German Science Foundation DFG (supporting R.H.). R.H. was visiting from the Ludwig-Maximilians-Universität München, München, Germany.

Author information

Authors and Affiliations

  1. Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Desmond C. Adler, Yu Chen, Robert Huber & James G. Fujimoto

  2. Lehrstuhl für BioMolekulare Optik, Fakultät für Physik, Ludwig-Maximilians-Universität München, München, 80538, Germany

    Robert Huber

  3. Lightlab Imaging, Westford, 01886, Massachusetts, USA

    Joseph Schmitt

  4. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, 02215, Massachusetts, USA

    James Connolly

Authors
  1. Desmond C. Adler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joseph Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James Connolly
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. James G. Fujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.C.A. and Y.C. were responsible for project planning, experimental work and data analysis. R.H. was responsible for experimental work. J.S. was responsible for experimental work, designed the equipment and provided technical material. J.C. was responsible for project planning and provided biological materials. J.G.F. obtained support, administered the project and was responsible for project planning.

Corresponding author

Correspondence to James G. Fujimoto.

Ethics declarations

Competing interests

J.G. Fujimoto and R. Huber receive royalties from intellectual property owned by the Massachusetts Institute of Technology (MIT) and licensed to LightLab Imaging. J. Schmitt is an employee of LightLab Imaging. D.C. Adler and Y. Chen have no competing financial interests in this work.

Supplementary information

Supplementary Information

Supplementary movie 1 (MOV 1990 kb)

Supplementary Information

Supplementary movie 2 (MOV 1741 kb)

Supplementary Information

Supplementary movie 3 (MOV 2039 kb)

Supplementary Information

Supplementary movie 4 (MOV 2047 kb)

Supplementary Information

Supplementary movie 5 (MOV 2173 kb)

Supplementary Information

Supplementary movie details (PDF 46 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adler, D., Chen, Y., Huber, R. et al. Three-dimensional endomicroscopy using optical coherence tomography. Nature Photon 1, 709–716 (2007). https://doi.org/10.1038/nphoton.2007.228

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nphoton.2007.228

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing