Abstract

Noninvasive in vivo functional optical imaging of the intact retina is demonstrated by using high-speed, ultrahigh-resolution optical coherence tomography (OCT). Imaging was performed with 2.8μm resolution at a rate of 24,000 axial scans per second. A white-light stimulus was applied to the dark-adapted rat retina, and the average reflectivities from different intraretinal layers were monitored as a function of time. A 10%–15% increase in the average amplitude reflectance of the photoreceptor outer segments was observed in response to the stimulus. The spatial distribution of the change in the OCT signal is consistent with an increase in backscatter from the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of OCT functional imaging in the intact retina.

© 2006 Optical Society of America

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M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
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K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
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2004 (3)

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2002 (1)

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F. Uehara, M. T. Matthes, D. Yasumura, and M. M. Lavail, Science 248, 1633 (1990).
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A. Grinvald, R. D. Frostig, E. Lieke, and R. Hildesheim, Physiol. Rev. 68, 1285 (1988).
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K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
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K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
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P. J. DeLint, T. T. Berendschot, J. van de Kraats, and D. van Norren, Invest. Ophthalmol. Visual Sci. 41, 282 (2000).

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K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
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P. J. DeLint, T. T. Berendschot, J. van de Kraats, and D. van Norren, Invest. Ophthalmol. Visual Sci. 41, 282 (2000).

Drexler, W.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
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A. Grinvald, R. D. Frostig, E. Lieke, and R. Hildesheim, Physiol. Rev. 68, 1285 (1988).
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George, J. S.

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D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, Invest. Ophthalmol. Visual Sci. 36, 57 (2005).

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K. Tsunoda, Y. Oguchi, G. Hanazono, and M. Tanifuji, Invest. Ophthalmol. Visual Sci. 45, 3820 (2004).
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Hermann, B.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
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Hildesheim, R.

A. Grinvald, R. D. Frostig, E. Lieke, and R. Hildesheim, Physiol. Rev. 68, 1285 (1988).
[PubMed]

Hitzenberger, C. K.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, Opt. Commun. 117, 43 (1995).
[CrossRef]

Homma, R.

R. U. Maheswari, H. Takaoka, H. Kadono, R. Homma, and M. Tanifuji, J. Neurosci. Methods 124, 83 (2003).
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Kadono, H.

R. U. Maheswari, H. Takaoka, H. Kadono, R. Homma, and M. Tanifuji, J. Neurosci. Methods 124, 83 (2003).
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Kamp, G.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, Opt. Commun. 117, 43 (1995).
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M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
[CrossRef]

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Kowalevicz, A.

Krupsky, S.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, Invest. Ophthalmol. Visual Sci. 36, 57 (2005).

Kwon, Y. H.

M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
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Lazebnik, M.

Lieke, E.

A. Grinvald, R. D. Frostig, E. Lieke, and R. Hildesheim, Physiol. Rev. 68, 1285 (1988).
[PubMed]

Maheswari, R. U.

R. U. Maheswari, H. Takaoka, H. Kadono, R. Homma, and M. Tanifuji, J. Neurosci. Methods 124, 83 (2003).
[CrossRef] [PubMed]

Marks, D. L.

Matthes, M. T.

F. Uehara, M. T. Matthes, D. Yasumura, and M. M. Lavail, Science 248, 1633 (1990).
[CrossRef] [PubMed]

Nassif, N.

Nassif, N. A.

Nelson, D. A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, Invest. Ophthalmol. Visual Sci. 36, 57 (2005).

Nelson, J. S.

Oguchi, Y.

K. Tsunoda, Y. Oguchi, G. Hanazono, and M. Tanifuji, Invest. Ophthalmol. Visual Sci. 45, 3820 (2004).
[CrossRef]

Park, B. H.

Perry, B.

Pflug, R.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Pierce, M. C.

Pokorny, J.

M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
[CrossRef]

Pollack, A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, Invest. Ophthalmol. Visual Sci. 36, 57 (2005).

Popov, S.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Potgieter, K.

Povazay, B.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Qiu, P.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Reitsamer, H.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Rosner, M.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, Invest. Ophthalmol. Visual Sci. 36, 57 (2005).

Sattmann, H.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Soliz, P.

M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
[CrossRef]

Srinivasan, V. J.

Takaoka, H.

R. U. Maheswari, H. Takaoka, H. Kadono, R. Homma, and M. Tanifuji, J. Neurosci. Methods 124, 83 (2003).
[CrossRef] [PubMed]

Tanifuji, M.

K. Tsunoda, Y. Oguchi, G. Hanazono, and M. Tanifuji, Invest. Ophthalmol. Visual Sci. 45, 3820 (2004).
[CrossRef]

R. U. Maheswari, H. Takaoka, H. Kadono, R. Homma, and M. Tanifuji, J. Neurosci. Methods 124, 83 (2003).
[CrossRef] [PubMed]

Targowski, P.

Taylor, J. R.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Tearney, G. J.

Tripathi, R.

Ts'o, D.

M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
[CrossRef]

Tsunoda, K.

K. Tsunoda, Y. Oguchi, G. Hanazono, and M. Tanifuji, Invest. Ophthalmol. Visual Sci. 45, 3820 (2004).
[CrossRef]

Uehara, F.

F. Uehara, M. T. Matthes, D. Yasumura, and M. M. Lavail, Science 248, 1633 (1990).
[CrossRef] [PubMed]

Unterhuber, A.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

van de Kraats, J.

P. J. DeLint, T. T. Berendschot, J. van de Kraats, and D. van Norren, Invest. Ophthalmol. Visual Sci. 41, 282 (2000).

van Norren, D.

P. J. DeLint, T. T. Berendschot, J. van de Kraats, and D. van Norren, Invest. Ophthalmol. Visual Sci. 41, 282 (2000).

Vanzetta, I.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, Invest. Ophthalmol. Visual Sci. 36, 57 (2005).

Villringer, A.

A. Villringer and B. Chance, Trends Neurosci. 20, 435 (1997).
[CrossRef] [PubMed]

Wojtkowski, M.

Yamauchi, A.

Yao, X. C.

Yasumura, D.

F. Uehara, M. T. Matthes, D. Yasumura, and M. M. Lavail, Science 248, 1633 (1990).
[CrossRef] [PubMed]

Yun, S. H.

Zimmerman, B.

M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
[CrossRef]

Appl. Opt. (1)

Invest. Ophthalmol. Visual Sci. (4)

P. J. DeLint, T. T. Berendschot, J. van de Kraats, and D. van Norren, Invest. Ophthalmol. Visual Sci. 41, 282 (2000).

K. Tsunoda, Y. Oguchi, G. Hanazono, and M. Tanifuji, Invest. Ophthalmol. Visual Sci. 45, 3820 (2004).
[CrossRef]

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, Invest. Ophthalmol. Visual Sci. 36, 57 (2005).

M. D. Abramoff, Y. H. Kwon, D. Ts'o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, Invest. Ophthalmol. Visual Sci. 47, 715 (2006).
[CrossRef]

J. Neurosci. Methods (1)

R. U. Maheswari, H. Takaoka, H. Kadono, R. Homma, and M. Tanifuji, J. Neurosci. Methods 124, 83 (2003).
[CrossRef] [PubMed]

Opt. Commun. (1)

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, Opt. Commun. 117, 43 (1995).
[CrossRef]

Opt. Express (2)

Opt. Lett. (3)

Physiol. Rev. (1)

A. Grinvald, R. D. Frostig, E. Lieke, and R. Hildesheim, Physiol. Rev. 68, 1285 (1988).
[PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, Proc. Natl. Acad. Sci. U.S.A. 103, 5066 (2006).
[CrossRef] [PubMed]

Science (1)

F. Uehara, M. T. Matthes, D. Yasumura, and M. M. Lavail, Science 248, 1633 (1990).
[CrossRef] [PubMed]

Trends Neurosci. (1)

A. Villringer and B. Chance, Trends Neurosci. 20, 435 (1997).
[CrossRef] [PubMed]

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Figures (4)

Fig. 1
Fig. 1

(A) OCT cross-sectional scan of the rat retina, with (B) an OCT fundus image and arrow showing the scan location. NFL, nerve fiber layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PR IS, photoreceptor inner segments; PR OS, photoreceptor outer segments; RPE, retinal pigment epithelium; CH, choroid.

Fig. 2
Fig. 2

Dark-adapted and preadapted functional response time courses compared with the baseline response. Each data point corresponds to the amplitude reflectance from the photoreceptor outer segments averaged over a single volume. Each error bar (± standard deviation) represents the standard deviation of the amplitude reflectance difference referenced to the stimulus onset ( t = 1.3 s ).

Fig. 3
Fig. 3

(A) Plot of the percent change in photoreceptor outer segment amplitude reflectance for t > 2.6 s compared with t < 1.3 s . (B) The data from one volume are unwrapped, flattened to the IS/OS boundary, and displayed as a log scale image for comparison with (A).

Fig. 4
Fig. 4

(A) Plot of the percent change in photoreceptor outer segment amplitude reflectance for t > 2.6 s compared with t < 1.3 s for the dark-adapted and preadapted trials. (B) The OCT data from one volume are unwrapped, flattened to the IS/OS boundary, and displayed as a log scale image for comparison with (A).

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