Abstract

Noninvasive monitoring of blood flow in retinal microcirculation may elucidate the progression and treatment of ocular disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Color Doppler optical coherence tomography (CDOCT) is a technique that allows simultaneous micrometer-scale resolution cross-sectional imaging of tissue microstructure and blood flow in living tissues. CDOCT is demonstrated for the first time in living human subjects for bidirectional blood-flow mapping of retinal vasculature.

© 2000 Optical Society of America

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  1. A. Alm, in Adler’s Physiology of the Eye: Clinical Application, W. M. Hart, ed. (Mosby, St. Louis, Mo., 1992), pp. 198–227.
  2. A. Harris, T. A. Ciulla, H. S. Chung, and B. Martin, Arch. Ophthalmol. 116, 1491 (1998).
    [CrossRef] [PubMed]
  3. C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Blood Velocimetry, A. P. Shepherd and P. Å. Öberg, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1990), pp. 349–383.
    [CrossRef]
  4. J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, Opt. Lett. 22, 1439 (1997).
    [CrossRef]
  5. S. Yazdanfar, A. M. Rollins, and J. A. Izatt, Proc. SPIE 3598, 177 (1999).
    [CrossRef]
  6. Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, Opt. Lett. 22, 64 (1997).
    [CrossRef] [PubMed]
  7. 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]
  8. A. M. Rollins and J. A. Izatt, Opt. Lett. 24, 1484 (1999).
    [CrossRef]
  9. S. Yazdanfar, M. D. Kulkarni, and J. A. Izatt, Opt. Express 1, 424 (1997), http://epubs.osa.org/opticsexpress .
    [CrossRef] [PubMed]
  10. M. D. Kulkarni, T. G. van Leeuwen, S. Yazdanfar, and J. A. Izatt, Opt. Lett. 23, 1057 (1998).
    [CrossRef]
  11. American National Standards Institute, “Safe use of lasers,” (Laser Institute of America, New York, 1993).
  12. E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
    [CrossRef] [PubMed]
  13. A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
    [CrossRef] [PubMed]
  14. T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
    [CrossRef] [PubMed]

1999 (3)

S. Yazdanfar, A. M. Rollins, and J. A. Izatt, Proc. SPIE 3598, 177 (1999).
[CrossRef]

A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
[CrossRef] [PubMed]

A. M. Rollins and J. A. Izatt, Opt. Lett. 24, 1484 (1999).
[CrossRef]

1998 (3)

T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
[CrossRef] [PubMed]

A. Harris, T. A. Ciulla, H. S. Chung, and B. Martin, Arch. Ophthalmol. 116, 1491 (1998).
[CrossRef] [PubMed]

M. D. Kulkarni, T. G. van Leeuwen, S. Yazdanfar, and J. A. Izatt, Opt. Lett. 23, 1057 (1998).
[CrossRef]

1997 (3)

1993 (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]

Alm, A.

A. Alm, in Adler’s Physiology of the Eye: Clinical Application, W. M. Hart, ed. (Mosby, St. Louis, Mo., 1992), pp. 198–227.

Barton, J. K.

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.

T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
[CrossRef] [PubMed]

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

Chung, H. S.

A. Harris, T. A. Ciulla, H. S. Chung, and B. Martin, Arch. Ophthalmol. 116, 1491 (1998).
[CrossRef] [PubMed]

Ciulla, T. A.

A. Harris, T. A. Ciulla, H. S. Chung, and B. Martin, Arch. Ophthalmol. 116, 1491 (1998).
[CrossRef] [PubMed]

Dave, D.

Dorschel, K.

A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
[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]

Friebel, M.

A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
[CrossRef] [PubMed]

Fujimoto, J. G.

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
[CrossRef] [PubMed]

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]

Grunwald, J. E.

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Blood Velocimetry, A. P. Shepherd and P. Å. Öberg, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1990), pp. 349–383.
[CrossRef]

Hahn, A.

A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
[CrossRef] [PubMed]

Harris, A.

A. Harris, T. A. Ciulla, H. S. Chung, and B. Martin, Arch. Ophthalmol. 116, 1491 (1998).
[CrossRef] [PubMed]

Hee, M. R.

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
[CrossRef] [PubMed]

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.

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
[CrossRef] [PubMed]

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]

Izatt, J. A.

Kulkarni, M. D.

Lin, C. P.

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
[CrossRef] [PubMed]

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.

T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
[CrossRef] [PubMed]

Martin, B.

A. Harris, T. A. Ciulla, H. S. Chung, and B. Martin, Arch. Ophthalmol. 116, 1491 (1998).
[CrossRef] [PubMed]

Milner, T. E.

T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
[CrossRef] [PubMed]

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

Muller, G.

A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
[CrossRef] [PubMed]

Nelson, J. S.

T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
[CrossRef] [PubMed]

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

Petrig, B. L.

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Blood Velocimetry, A. P. Shepherd and P. Å. Öberg, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1990), pp. 349–383.
[CrossRef]

Puliafito, C. A.

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
[CrossRef] [PubMed]

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]

Riva, C. E.

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Blood Velocimetry, A. P. Shepherd and P. Å. Öberg, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1990), pp. 349–383.
[CrossRef]

Roggan, A.

A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
[CrossRef] [PubMed]

Rollins, A. M.

S. Yazdanfar, A. M. Rollins, and J. A. Izatt, Proc. SPIE 3598, 177 (1999).
[CrossRef]

A. M. Rollins and J. A. Izatt, Opt. Lett. 24, 1484 (1999).
[CrossRef]

Schuman, J. S.

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
[CrossRef] [PubMed]

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]

Smithies, D. J.

T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
[CrossRef] [PubMed]

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.

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, Opt. Lett. 18, 1864 (1993).
[CrossRef] [PubMed]

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]

van Leeuwen, T. G.

Welch, A. J.

Yazdanfar, S.

Arch. Ophthalmol. (1)

A. Harris, T. A. Ciulla, H. S. Chung, and B. Martin, Arch. Ophthalmol. 116, 1491 (1998).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

A. Roggan, M. Friebel, K. Dorschel, A. Hahn, and G. Muller, J. Biomed. Opt. 4, 36 (1999).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (5)

Phys. Med. Biol. (1)

T. Lindmo, D. J. Smithies, Z. Chen, J. S. Nelson, and T. E. Milner, Phys. Med. Biol. 43, 3045 (1998).
[CrossRef] [PubMed]

Proc. SPIE (1)

S. Yazdanfar, A. M. Rollins, and J. A. Izatt, Proc. SPIE 3598, 177 (1999).
[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 (3)

A. Alm, in Adler’s Physiology of the Eye: Clinical Application, W. M. Hart, ed. (Mosby, St. Louis, Mo., 1992), pp. 198–227.

C. E. Riva, B. L. Petrig, and J. E. Grunwald, in Laser-Doppler Blood Velocimetry, A. P. Shepherd and P. Å. Öberg, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1990), pp. 349–383.
[CrossRef]

American National Standards Institute, “Safe use of lasers,” (Laser Institute of America, New York, 1993).

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Figures (3)

Fig. 1
Fig. 1

Schematic of the retinal CDOCT Michelson interferometer. OCT measures interference between light reflected from a tissue sample and a scanning reference mirror, which provides depth ranging in the sample. The axial spatial resolution is determined by the coherence length of the light source, and the lateral resolution is determined by the beam-spot size in the sample. A 78-D condensing lens projects the image of the retina onto the image plane indicated by the dashed line, and the image plane is relayed onto the fiber tip plane by a pair of lenses. An xy-scanning mirror pair permits transverse imaging in arbitrary linear and circular scan patterns. A CCD camera sensitive to low-intensity near-infrared light was used to visualize the exact scan location on the fundus simultaneous with CDOCT imaging. BPF, bandpass filter; A/D’s, analog-to-digital converters; I, Q, in-phase and quadrature signal components, respectively, after demodulation.

Fig. 2
Fig. 2

A, in vivo CDOCT image of bidirectional flow in the human retina superior to the optic nerve head. Structural information is encoded in gray scale, where white indicates high reflectivity (e.g., RPE–CC), and black indicates low reflectivity (e.g., vitreous humor). For velocity information, the direction and magnitude of blood flow are encoded by color (red or blue) and intensity, respectively. The axial dimensions indicate optical depth. CDOCT is able to distinguish various layers of tissue as well as quantify blood-flow magnitude and direction in sub-100-µm-diameter retinal blood vessels. ILM, inner limiting membrane. B, retinal surface profile A before (unprocessed) and after correction of motion artifact, obtained by use of the thresholding algorithm described in the text. Assuming that the high-spatial-frequency components of this profile result from motion artifacts and the low-frequency components represent the natural topography of the retina, we low-pass filtered the raw profile 2.5 cycles/mm to indicate the desired profile. Each axial scan was then aligned with the filtered profile of the retinal surface. Note that, if all oscillations are removed (i.e., low-pass cutoff of 0 cycles/mm), the processing will completely flatten the retinal profile.

Fig. 3
Fig. 3

Depth-resolved raw flow distribution corresponding to a single-scan segment extracted from a CDOCT image of a retinal vessel. The flow profile was detected and digitized in 10.3 ms and thus it does not exhibit any effects of the pulsatile nature of the flow. A parabolic fit to the data indicates laminar flow and extracts parameters such as vessel depth and diameter (176 µm, assuming a tissue refractive index of 1.38). The standard deviation of the residuals, as determined with nonlinear least-squares regression, was 450 Hz, with a centerline frequency coefficient of variation of 1.13%. The arrow at the proximal end of the profile indicates the effect of multiple scattering of light as it propagates into the vessel.

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