Abstract

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-µm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.

© 1997 Optical Society of America

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References

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  1. F. W. Kremkau, Diagnostic Ultrasound (Saunders, Philadelphia, Pa., 1989).
  2. R. Bonner and R. Nossal, Appl. Opt. 20, 2097 (1981).
    [CrossRef] [PubMed]
  3. C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Flowmetry, A. P. Shepherd and P. A. Oberg, eds. (Kluwer, Boston, Mass., 1990), pp. 349–409.
    [CrossRef]
  4. J. A. Izatt and M. D. Kulkarni, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), postdeadline paper CPD3-1.
  5. Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, Opt. Lett. 22, 64 (1997).
    [CrossRef] [PubMed]
  6. Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
    [CrossRef]
  7. J. Barton, J. A. Izatt, M. D. Kulkarni, and A. J. Welch, Proc. SPIE 2970, 266 (1997).
    [CrossRef]
  8. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
    [CrossRef] [PubMed]
  9. Animal experiments were conducted under a protocol approved by the Institutional Animal Care and Use Committee of the Case Western Reserve University School of Medicine.
  10. H. D. Papenfuss, J. F. Gross, M. Intaglietta, and F. A. Treese, Microvasc. Res. 18, 311 (1979).
    [CrossRef] [PubMed]
  11. J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
    [CrossRef]
  12. M. D. Kulkarni and J. A. Izatt, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), pp. 59–60.
  13. S. H. Nawab and T. F. Quatieri, in Advanced Topics in Signal Processing, J. S. Lim and A. V. Oppenheim, eds. (Prentice-Hall, Englewood Cliffs, N.J., 1988), Chap. 6.
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    [CrossRef] [PubMed]

1997 (3)

Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
[CrossRef]

J. Barton, J. A. Izatt, M. D. Kulkarni, and A. J. Welch, Proc. SPIE 2970, 266 (1997).
[CrossRef]

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, Opt. Lett. 22, 64 (1997).
[CrossRef] [PubMed]

1996 (1)

J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
[CrossRef]

1995 (1)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

1981 (1)

1979 (1)

H. D. Papenfuss, J. F. Gross, M. Intaglietta, and F. A. Treese, Microvasc. Res. 18, 311 (1979).
[CrossRef] [PubMed]

Barton, J.

J. Barton, J. A. Izatt, M. D. Kulkarni, and A. J. Welch, Proc. SPIE 2970, 266 (1997).
[CrossRef]

Bonner, R.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Chen, Z.

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, Opt. Lett. 22, 64 (1997).
[CrossRef] [PubMed]

Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
[CrossRef]

Dave, D.

Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
[CrossRef]

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, Opt. Lett. 22, 64 (1997).
[CrossRef] [PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Fujimoto, J. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Gross, J. F.

H. D. Papenfuss, J. F. Gross, M. Intaglietta, and F. A. Treese, Microvasc. Res. 18, 311 (1979).
[CrossRef] [PubMed]

Grunwald, J. E.

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Flowmetry, A. P. Shepherd and P. A. Oberg, eds. (Kluwer, Boston, Mass., 1990), pp. 349–409.
[CrossRef]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Intaglietta, M.

H. D. Papenfuss, J. F. Gross, M. Intaglietta, and F. A. Treese, Microvasc. Res. 18, 311 (1979).
[CrossRef] [PubMed]

Izatt, J. A.

J. Barton, J. A. Izatt, M. D. Kulkarni, and A. J. Welch, Proc. SPIE 2970, 266 (1997).
[CrossRef]

J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
[CrossRef]

M. D. Kulkarni and J. A. Izatt, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), pp. 59–60.

J. A. Izatt and M. D. Kulkarni, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), postdeadline paper CPD3-1.

Kobayashi, K.

J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
[CrossRef]

Kremkau, F. W.

F. W. Kremkau, Diagnostic Ultrasound (Saunders, Philadelphia, Pa., 1989).

Kulkarni, M. D.

J. Barton, J. A. Izatt, M. D. Kulkarni, and A. J. Welch, Proc. SPIE 2970, 266 (1997).
[CrossRef]

J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
[CrossRef]

M. D. Kulkarni and J. A. Izatt, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), pp. 59–60.

J. A. Izatt and M. D. Kulkarni, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), postdeadline paper CPD3-1.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Lindmo, T.

Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
[CrossRef]

Milner, T. E.

Nawab, S. H.

S. H. Nawab and T. F. Quatieri, in Advanced Topics in Signal Processing, J. S. Lim and A. V. Oppenheim, eds. (Prentice-Hall, Englewood Cliffs, N.J., 1988), Chap. 6.

Nelson, J. S.

Nossal, R.

Papenfuss, H. D.

H. D. Papenfuss, J. F. Gross, M. Intaglietta, and F. A. Treese, Microvasc. Res. 18, 311 (1979).
[CrossRef] [PubMed]

Petrig, B. L.

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Flowmetry, A. P. Shepherd and P. A. Oberg, eds. (Kluwer, Boston, Mass., 1990), pp. 349–409.
[CrossRef]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Quatieri, T. F.

S. H. Nawab and T. F. Quatieri, in Advanced Topics in Signal Processing, J. S. Lim and A. V. Oppenheim, eds. (Prentice-Hall, Englewood Cliffs, N.J., 1988), Chap. 6.

Riva, C. E.

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Flowmetry, A. P. Shepherd and P. A. Oberg, eds. (Kluwer, Boston, Mass., 1990), pp. 349–409.
[CrossRef]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Sivak, M. V.

J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
[CrossRef]

Smithies, D.

Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
[CrossRef]

Srinivas, S.

Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
[CrossRef]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Treese, F. A.

H. D. Papenfuss, J. F. Gross, M. Intaglietta, and F. A. Treese, Microvasc. Res. 18, 311 (1979).
[CrossRef] [PubMed]

Wang, H. W.

J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
[CrossRef]

Wang, X. J.

Welch, A. J.

J. Barton, J. A. Izatt, M. D. Kulkarni, and A. J. Welch, Proc. SPIE 2970, 266 (1997).
[CrossRef]

Appl. Opt. (1)

IEEE J. Sel. Topics Quantum Electron. (1)

J. A. Izatt, M. D. Kulkarni, H. W. Wang, K. Kobayashi, and M. V. Sivak, IEEE J. Sel. Topics Quantum Electron. 2, 1017 (1996).
[CrossRef]

Microvasc. Res. (1)

H. D. Papenfuss, J. F. Gross, M. Intaglietta, and F. A. Treese, Microvasc. Res. 18, 311 (1979).
[CrossRef] [PubMed]

Opt. Lett. (2)

Proc. SPIE (2)

Z. Chen, T. E. Milner, S. Srinivas, T. Lindmo, D. Smithies, D. Dave, and J. S. Nelson, Proc. SPIE 2981, 112 (1997).
[CrossRef]

J. Barton, J. A. Izatt, M. D. Kulkarni, and A. J. Welch, Proc. SPIE 2970, 266 (1997).
[CrossRef]

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Other (6)

Animal experiments were conducted under a protocol approved by the Institutional Animal Care and Use Committee of the Case Western Reserve University School of Medicine.

F. W. Kremkau, Diagnostic Ultrasound (Saunders, Philadelphia, Pa., 1989).

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Flowmetry, A. P. Shepherd and P. A. Oberg, eds. (Kluwer, Boston, Mass., 1990), pp. 349–409.
[CrossRef]

J. A. Izatt and M. D. Kulkarni, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), postdeadline paper CPD3-1.

M. D. Kulkarni and J. A. Izatt, in Conference on Lasers and Electro-Optics, Vol. 9 of 1996 OSA Technical Digest Series (Optical Society of America, Washington, D.C., 1996), pp. 59–60.

S. H. Nawab and T. F. Quatieri, in Advanced Topics in Signal Processing, J. S. Lim and A. V. Oppenheim, eds. (Prentice-Hall, Englewood Cliffs, N.J., 1988), Chap. 6.

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Figures (4)

Fig. 1
Fig. 1

Schematic diagram of the fiber-optic color Doppler OCT scanner and Doppler processing signal path. A superluminescent diode was used as the low-coherence illumination source (λ=1270 nm, Δλ=35 nm FWHM, P=0.6 mW, coherence length 20  µm FWHM). BPF, bandpass filter; A/D’s, analog–digital converters. I, in-phase; Q, quadrature.

Fig. 2
Fig. 2

In vivo cross-sectional magnitude-only OCT image of subsurface tissue structure in a hamster dorsal skin-flap surgical preparation. Blood vessels are not apparent. The image was acquired in 40  s and contains 200 (h)×512 v pixels.

Fig. 3
Fig. 3

STFT spectrograms of the complex demodulated A-scan data obtained at the locations of vertical lines A and B in Fig.  2. Each horizontal row of the image represents the FFT of a 32-element windowed subset of the 512-element digitized A-scan data, with the window position centered on the row height. The mean velocity of flow at each depth was estimated from the centroid frequency of each FFT (white line). The STFT spectrograms were averaged five times.

Fig. 4
Fig. 4

In vivo color Doppler OCT image obtained by overlaying the magnitude-only OCT image with color-coded 2D Doppler velocity data. The presence of an artery–vein pair was confirmed by comparison with histology. Only velocities greater than +1.4 and less than -0.6 mm/s are displayed for clarity. The spatial resolution of the Doppler velocity data was 44 µm in depth by 14 µm lateral diameter (corresponding to a 7-pl blood sampling volume), and the velocity-estimation precision was 0.56 mm/s. The magnitude and velocity data were averaged five times.

Equations (4)

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i˜dt=Atcos2πfr-fst+ϕt.
idt=Atexp-j2πfst+ϕt.
Fidt=Sf-fs.
Snts, f=m=-N/2N/2-1idn+mtswmtsexp-j2πfmts.

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