Abstract

Real time, high-speed image stabilization with a retinal tracking scanning laser ophthalmoscope (TSLO) enables new approaches to established diagnostics. Large frequency range (DC to 19 kHz), wide-field (40-deg) stabilized Doppler flowmetry imaging was demonstrated in initial human subject tests. The fundus imaging method is a quasi-confocal line-scanning laser ophthalmoscope (LSLO). The retinal tracking system uses a confocal reflectometer with a closed loop optical servo system to lock onto features in the ocular fundus and automatically re-lock after blinks. By performing a slow scan with the laser line imager, frequency-resolved retinal perfusion and vascular flow images were obtained free of eye motion artifacts. Normal adult subjects and patients were tested with and without mydriasis to characterize flow imaging performance.

©2004 Optical Society of America

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References

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    [PubMed]
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  4. A. E. Elsner, D. Bartsch, J. J. Weiter, and M. E. Hartnett, “New devices in retinal imaging and functional evaluation,” in Practical Atlas of Retinal Disease and Therapy, W. Freeman, ed. (Lippincott-Raven, New York,1998).
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    [Crossref]
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    [Crossref]
  7. A. E. Ennos, “Speckle interferometry,” in Laser Speckle and Related Topics, J. C. Dainty, ed. (Springer-Verlag, Berlin,1984).
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    [Crossref]
  10. R. Bonner and R. Nossal, “Model for laser Doppler measurements of blood flow in tissue,” Appl. Opt. 20, 2097–2107 (1981).
    [Crossref] [PubMed]
  11. C. Riva, B. Ross, and G. Benedek, “Laser Doppler measurements of blood flow in capillary tubes and retinal arteries,” Invest. Ophthalmol. 11, 936–944 (1972).
    [PubMed]
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    [Crossref] [PubMed]
  13. N. Konishi and H. Fujii, “Real-time visualization of retinal microcirculation by laser flowgraphy,” Opt. Eng. 34, 753–757 (1995).
    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref]
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    [Crossref]
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  23. R. Daniel Ferguson, “Servo tracking system utilizing phase-sensitive detection of reflectance variation,” U.S. Patents #5,767,941 and #5,943,115.
  24. D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, “Image stabilization for scanning laser ophthalmoscopy,” Opt. Express 10, 1542–1549 (2002), http://www.opticsexpress.org/abstract.cfm?URI=OPEX-10-26-1542.
    [Crossref] [PubMed]
  25. D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, “Compact scanning laser ophthalmoscope with high speed retinal tracker,” Appl. Opt. 42, 4621–4632 (2003).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]

2003 (2)

2002 (1)

2001 (1)

G. Michelson, J. Welzenbach, I. Pal, and J. Harazny, “Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry,” Int. Ophthalmol. 23, 327–335 (2001).
[Crossref]

2000 (1)

1999 (2)

J. D. Briers, G. Richards, and X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4, 164–175 (1999).
[Crossref] [PubMed]

T. G. van Leeuwen, M. D. Kulkarni, S. Yazdanfar, A. M. Rollins, and J. A. Izatt, “High-flow-velocity and shear-rate imaging by use of color Doppler optical coherence tomography,” Opt. Lett. 24, 1584–1586 (1999).
[Crossref]

1997 (1)

1996 (2)

G. Michelson, B. Schmauss, M.J. Langhans, J. Harazny, and M.J.M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma 5, 99–105 (1996).
[Crossref] [PubMed]

M. E. Hartnett, J. J. Weiter, G. Staurenghi, and A. E. Elsner, “Deep retinal vascular anomalous complexes in advanced age-related macular degeneration,” Ophthalmol.,  103, 2042–2053 (1996).

1995 (2)

N. Konishi and H. Fujii, “Real-time visualization of retinal microcirculation by laser flowgraphy,” Opt. Eng. 34, 753–757 (1995).
[Crossref]

X. J. Wang, T. E. Milner, and J. S. Nelson, “Characterization of fluid flow velocity by optical Doppler tomography,” Opt. Lett. 20, 1337–1339 (1995).
[Crossref] [PubMed]

1993 (1)

J. D. Briers, “Speckle fluctuations and biomedical optics: implications and applications,” Opt. Eng. 32, 277–283 (1993).
[Crossref]

1988 (1)

1981 (2)

R. Bonner and R. Nossal, “Model for laser Doppler measurements of blood flow in tissue,” Appl. Opt. 20, 2097–2107 (1981).
[Crossref] [PubMed]

A. F. Fercher and J. D. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37, 326–329 (1981).
[Crossref]

1974 (1)

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–832 (1974).
[Crossref] [PubMed]

1973 (1)

J. J. Weiter, R. A. Schachar, and J. T. Ernest, “Control of intraocular blood flow, I. Intraocular pressure,” Invest Ophthalmol. 12, 327–331 (1973).
[PubMed]

1972 (1)

C. Riva, B. Ross, and G. Benedek, “Laser Doppler measurements of blood flow in capillary tubes and retinal arteries,” Invest. Ophthalmol. 11, 936–944 (1972).
[PubMed]

1970 (1)

D. Gabor, “Laser speckle and its elimination,” IBM J. Res. Dev. 14, 509–514 (1970).
[Crossref]

Alm, A.

A. Alm, “Ocular circulation,” in Alder’s Physiology of the Eye. Clinical Applications, W. M. Hart, ed. (Mosby-Year Book, St. Louis,1992).

Barton, J. K.

Bartsch, D.

A. E. Elsner, D. Bartsch, J. J. Weiter, and M. E. Hartnett, “New devices in retinal imaging and functional evaluation,” in Practical Atlas of Retinal Disease and Therapy, W. Freeman, ed. (Lippincott-Raven, New York,1998).

Benedek, G.

C. Riva, B. Ross, and G. Benedek, “Laser Doppler measurements of blood flow in capillary tubes and retinal arteries,” Invest. Ophthalmol. 11, 936–944 (1972).
[PubMed]

Ben-Sira, I.

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–832 (1974).
[Crossref] [PubMed]

Bonner, R.

Bouma, B. E.

Briers, J. D.

J. D. Briers, G. Richards, and X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4, 164–175 (1999).
[Crossref] [PubMed]

J. D. Briers, “Speckle fluctuations and biomedical optics: implications and applications,” Opt. Eng. 32, 277–283 (1993).
[Crossref]

A. F. Fercher and J. D. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37, 326–329 (1981).
[Crossref]

Cense, B.

Chen, T. C.

Dadusc, G.

D. X. Hammer, R.D. Ferguson, T. Ustun, G. Dadusc, and R.H. Webb, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” in Ophthalmic Technologies XIV, F. Manns, P. G. Söderberg, and A. Ho, eds., Proc. SPIE5314, 161–169 (2004).

de Boer, J. F.

Elsner, A. E.

D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, “Compact scanning laser ophthalmoscope with high speed retinal tracker,” Appl. Opt. 42, 4621–4632 (2003).
[Crossref] [PubMed]

D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, “Image stabilization for scanning laser ophthalmoscopy,” Opt. Express 10, 1542–1549 (2002), http://www.opticsexpress.org/abstract.cfm?URI=OPEX-10-26-1542.
[Crossref] [PubMed]

M. E. Hartnett, J. J. Weiter, G. Staurenghi, and A. E. Elsner, “Deep retinal vascular anomalous complexes in advanced age-related macular degeneration,” Ophthalmol.,  103, 2042–2053 (1996).

A. E. Elsner, D. Bartsch, J. J. Weiter, and M. E. Hartnett, “New devices in retinal imaging and functional evaluation,” in Practical Atlas of Retinal Disease and Therapy, W. Freeman, ed. (Lippincott-Raven, New York,1998).

Ennos, A. E.

A. E. Ennos, “Speckle interferometry,” in Laser Speckle and Related Topics, J. C. Dainty, ed. (Springer-Verlag, Berlin,1984).

Ernest, J. T.

J. J. Weiter, R. A. Schachar, and J. T. Ernest, “Control of intraocular blood flow, I. Intraocular pressure,” Invest Ophthalmol. 12, 327–331 (1973).
[PubMed]

Fercher, A. F.

A. F. Fercher and J. D. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37, 326–329 (1981).
[Crossref]

Ferguson, R. D.

Ferguson, R. Daniel

R. Daniel Ferguson, “Servo tracking system utilizing phase-sensitive detection of reflectance variation,” U.S. Patents #5,767,941 and #5,943,115.

Ferguson, R.D.

D. X. Hammer, R.D. Ferguson, T. Ustun, G. Dadusc, and R.H. Webb, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” in Ophthalmic Technologies XIV, F. Manns, P. G. Söderberg, and A. Ho, eds., Proc. SPIE5314, 161–169 (2004).

Fujii, H.

N. Konishi and H. Fujii, “Real-time visualization of retinal microcirculation by laser flowgraphy,” Opt. Eng. 34, 753–757 (1995).
[Crossref]

Gabor, D.

D. Gabor, “Laser speckle and its elimination,” IBM J. Res. Dev. 14, 509–514 (1970).
[Crossref]

Goodman, J. W.

J. W. Goodman, “Statistical properties of laser speckle patterns,” in Laser Speckle and Related Topics, J. C. Dainty, ed. (Springer-Verlag, Berlin,1984).

Groh, M.J.M.

G. Michelson, B. Schmauss, M.J. Langhans, J. Harazny, and M.J.M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma 5, 99–105 (1996).
[Crossref] [PubMed]

Hammer, D. X.

Harazny, J.

G. Michelson, J. Welzenbach, I. Pal, and J. Harazny, “Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry,” Int. Ophthalmol. 23, 327–335 (2001).
[Crossref]

G. Michelson, B. Schmauss, M.J. Langhans, J. Harazny, and M.J.M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma 5, 99–105 (1996).
[Crossref] [PubMed]

Hartnett, M. E.

M. E. Hartnett, J. J. Weiter, G. Staurenghi, and A. E. Elsner, “Deep retinal vascular anomalous complexes in advanced age-related macular degeneration,” Ophthalmol.,  103, 2042–2053 (1996).

A. E. Elsner, D. Bartsch, J. J. Weiter, and M. E. Hartnett, “New devices in retinal imaging and functional evaluation,” in Practical Atlas of Retinal Disease and Therapy, W. Freeman, ed. (Lippincott-Raven, New York,1998).

He, X. W.

J. D. Briers, G. Richards, and X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4, 164–175 (1999).
[Crossref] [PubMed]

Izatt, J. A.

Konishi, N.

N. Konishi and H. Fujii, “Real-time visualization of retinal microcirculation by laser flowgraphy,” Opt. Eng. 34, 753–757 (1995).
[Crossref]

Kulkarni, M. D.

Langhans, M.J.

G. Michelson, B. Schmauss, M.J. Langhans, J. Harazny, and M.J.M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma 5, 99–105 (1996).
[Crossref] [PubMed]

Leeuwen, T. G. van

Magill, J. C.

Michelson, G.

G. Michelson, J. Welzenbach, I. Pal, and J. Harazny, “Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry,” Int. Ophthalmol. 23, 327–335 (2001).
[Crossref]

G. Michelson, B. Schmauss, M.J. Langhans, J. Harazny, and M.J.M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma 5, 99–105 (1996).
[Crossref] [PubMed]

Milner, T. E.

Nassif, N.

Nelson, J. S.

Nossal, R.

Pal, I.

G. Michelson, J. Welzenbach, I. Pal, and J. Harazny, “Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry,” Int. Ophthalmol. 23, 327–335 (2001).
[Crossref]

Park, B. H.

Petrig, B. L.

Pierce, M. C.

Richards, G.

J. D. Briers, G. Richards, and X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4, 164–175 (1999).
[Crossref] [PubMed]

Riva, C.

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–832 (1974).
[Crossref] [PubMed]

C. Riva, B. Ross, and G. Benedek, “Laser Doppler measurements of blood flow in capillary tubes and retinal arteries,” Invest. Ophthalmol. 11, 936–944 (1972).
[PubMed]

Riva, C. E.

Rollins, A. M.

Ross, B.

C. Riva, B. Ross, and G. Benedek, “Laser Doppler measurements of blood flow in capillary tubes and retinal arteries,” Invest. Ophthalmol. 11, 936–944 (1972).
[PubMed]

Schachar, R. A.

J. J. Weiter, R. A. Schachar, and J. T. Ernest, “Control of intraocular blood flow, I. Intraocular pressure,” Invest Ophthalmol. 12, 327–331 (1973).
[PubMed]

Schmauss, B.

G. Michelson, B. Schmauss, M.J. Langhans, J. Harazny, and M.J.M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma 5, 99–105 (1996).
[Crossref] [PubMed]

Staurenghi, G.

M. E. Hartnett, J. J. Weiter, G. Staurenghi, and A. E. Elsner, “Deep retinal vascular anomalous complexes in advanced age-related macular degeneration,” Ophthalmol.,  103, 2042–2053 (1996).

Tanaka, T.

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–832 (1974).
[Crossref] [PubMed]

Tearney, G. J.

Ustun, T.

D. X. Hammer, R.D. Ferguson, T. Ustun, G. Dadusc, and R.H. Webb, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” in Ophthalmic Technologies XIV, F. Manns, P. G. Söderberg, and A. Ho, eds., Proc. SPIE5314, 161–169 (2004).

Wang, X. J.

Webb, R. H.

Webb, R.H.

D. X. Hammer, R.D. Ferguson, T. Ustun, G. Dadusc, and R.H. Webb, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” in Ophthalmic Technologies XIV, F. Manns, P. G. Söderberg, and A. Ho, eds., Proc. SPIE5314, 161–169 (2004).

Weiter, J. J.

M. E. Hartnett, J. J. Weiter, G. Staurenghi, and A. E. Elsner, “Deep retinal vascular anomalous complexes in advanced age-related macular degeneration,” Ophthalmol.,  103, 2042–2053 (1996).

J. J. Weiter, R. A. Schachar, and J. T. Ernest, “Control of intraocular blood flow, I. Intraocular pressure,” Invest Ophthalmol. 12, 327–331 (1973).
[PubMed]

A. E. Elsner, D. Bartsch, J. J. Weiter, and M. E. Hartnett, “New devices in retinal imaging and functional evaluation,” in Practical Atlas of Retinal Disease and Therapy, W. Freeman, ed. (Lippincott-Raven, New York,1998).

Welch, A. J.

Welzenbach, J.

G. Michelson, J. Welzenbach, I. Pal, and J. Harazny, “Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry,” Int. Ophthalmol. 23, 327–335 (2001).
[Crossref]

White, B. R

White, M. A.

Yazdanfar, S.

Appl. Opt. (3)

IBM J. Res. Dev. (1)

D. Gabor, “Laser speckle and its elimination,” IBM J. Res. Dev. 14, 509–514 (1970).
[Crossref]

Int. Ophthalmol. (1)

G. Michelson, J. Welzenbach, I. Pal, and J. Harazny, “Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry,” Int. Ophthalmol. 23, 327–335 (2001).
[Crossref]

Invest Ophthalmol. (1)

J. J. Weiter, R. A. Schachar, and J. T. Ernest, “Control of intraocular blood flow, I. Intraocular pressure,” Invest Ophthalmol. 12, 327–331 (1973).
[PubMed]

Invest. Ophthalmol. (1)

C. Riva, B. Ross, and G. Benedek, “Laser Doppler measurements of blood flow in capillary tubes and retinal arteries,” Invest. Ophthalmol. 11, 936–944 (1972).
[PubMed]

J. Biomed. Opt. (1)

J. D. Briers, G. Richards, and X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4, 164–175 (1999).
[Crossref] [PubMed]

J. Glaucoma (1)

G. Michelson, B. Schmauss, M.J. Langhans, J. Harazny, and M.J.M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma 5, 99–105 (1996).
[Crossref] [PubMed]

Ophthalmol. (1)

M. E. Hartnett, J. J. Weiter, G. Staurenghi, and A. E. Elsner, “Deep retinal vascular anomalous complexes in advanced age-related macular degeneration,” Ophthalmol.,  103, 2042–2053 (1996).

Opt. Commun. (1)

A. F. Fercher and J. D. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37, 326–329 (1981).
[Crossref]

Opt. Eng. (2)

J. D. Briers, “Speckle fluctuations and biomedical optics: implications and applications,” Opt. Eng. 32, 277–283 (1993).
[Crossref]

N. Konishi and H. Fujii, “Real-time visualization of retinal microcirculation by laser flowgraphy,” Opt. Eng. 34, 753–757 (1995).
[Crossref]

Opt. Express (2)

Opt. Lett. (4)

Science (1)

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–832 (1974).
[Crossref] [PubMed]

Other (6)

A. E. Ennos, “Speckle interferometry,” in Laser Speckle and Related Topics, J. C. Dainty, ed. (Springer-Verlag, Berlin,1984).

J. W. Goodman, “Statistical properties of laser speckle patterns,” in Laser Speckle and Related Topics, J. C. Dainty, ed. (Springer-Verlag, Berlin,1984).

A. E. Elsner, D. Bartsch, J. J. Weiter, and M. E. Hartnett, “New devices in retinal imaging and functional evaluation,” in Practical Atlas of Retinal Disease and Therapy, W. Freeman, ed. (Lippincott-Raven, New York,1998).

A. Alm, “Ocular circulation,” in Alder’s Physiology of the Eye. Clinical Applications, W. M. Hart, ed. (Mosby-Year Book, St. Louis,1992).

D. X. Hammer, R.D. Ferguson, T. Ustun, G. Dadusc, and R.H. Webb, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” in Ophthalmic Technologies XIV, F. Manns, P. G. Söderberg, and A. Ho, eds., Proc. SPIE5314, 161–169 (2004).

R. Daniel Ferguson, “Servo tracking system utilizing phase-sensitive detection of reflectance variation,” U.S. Patents #5,767,941 and #5,943,115.

Supplementary Material (5)

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Figures (8)

Fig. 1.
Fig. 1. (2.3 MB) Video and x-y eye positions during automatic re-lock after blinks. Slewing is caused by tracking biases that move the tracking mirrors when lock is lost at high servo gain

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Fig. 2.
Fig. 2. Diagram illustrating the slow scan technique for SDF (a) and for the HRF (b). The order of the BTC scan sequence is numbered on the diagram. The scan equation is shown below the diagram for each type. After Fourier transformation, the data cube is displayed as a video where individual frames are created by binning individual frequencies with a moving window.

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Fig. 3.
Fig. 3. (2.0 MB) Reconstructed image and blood flow video for a healthy 24 year old subject.

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Fig. 4.
Fig. 4. (2.2 MB) Reconstructed image and blood flow video for normal subject with light pigmentation.

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Fig. 5.
Fig. 5. (3.0 MB) Reconstructed image and blood flow video for patient with central serous chorioretinopathy (indicated by blue arrows).

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Fig. 6.
Fig. 6. Laminar Poiseuille flow measured in a major nasal retinal artery (indicated by yellow box) from a high-frequency, high-magnification scan. The FWHM vessel edges (circles) are plotted and fit to a parabolic curve. The frequency of flow in the vessel is indicated up to the measured resolution limit of the imaging system. The maximum detectable frequency in that vessel is also indicated (diamond, error bars indicate range of bin). Estimated peak velocity was 4.6±0.4 cm/s.

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Fig. 7.
Fig. 7. (2.3 MB) Reconstructed image and blood flow video for macular degeneration patient showing reduced perfusion in the macula.

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Fig. 8.
Fig. 8. False color composite blood flow images for second normal subject (a,d) and both patients (b,c,e,f). Upper row (a-c) shows images created with individually normalized frequencies bins and lower row shows images created when the composite image was normalized to the power in each bin. Red: f < 400 Hz, Green: f = 400 – 1000 Hz, Blue: f ~ 1000 Hz.

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Equations (1)

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u p = f p λ n sin ⁡ θ B

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