Abstract

We present label-free functional photoacoustic imaging of the ocular microvasculature in living animals. The anterior segment of an adult mouse was imaged with a laser exposure level well within the American National Standards Institute safety standards. Individual red blood cells traveling along the iris capillaries were clearly resolved, and the hemoglobin oxygen saturation in the iris microvasculature was imaged spectrally. We believe that photoacoustic imaging has the potential to advance the diagnosis and treatment of ocular diseases in humans.

© 2009 Optical Society of America

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References

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  1. J. R. Pleis and J. W. Lucas, Summary Health Statistics for U.S. Adults: National Health Interview Survey (National Center for Health Statistics, 2007).
  2. L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
    [CrossRef] [PubMed]
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    [CrossRef]
  4. X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  6. K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
    [CrossRef] [PubMed]
  7. American National Standards Institute Inc. (ANSI), ANSI Z136.1-2007: American National Standard for Safe Use of Lasers (ANSI, 2007).
  8. Z. Xie, S. Jiao, H. F. Zhang, and C. A. Puliafito, Opt. Lett. 34, 1771 (2009).
    [CrossRef] [PubMed]

2009

2008

2006

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef] [PubMed]

2003

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

1994

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Aiello, L. M.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Aiello, L. P.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Arrigg, P. G.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Avery, R. L.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Ferrara, N.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Hu, S.

Hurley, B. R.

B. R. Hurley and C. D. Regillo, in Retinal Angiography and Optical Coherence Tomography, J.Fernando Arevalo, ed. (Springer, 2009), pp. 27-42.
[CrossRef]

Iwamoto, M. A.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Jampel, H. D.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Jiao, S.

Keyt, B. A.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

King, G. L.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Ku, G.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Lucas, J. W.

J. R. Pleis and J. W. Lucas, Summary Health Statistics for U.S. Adults: National Health Interview Survey (National Center for Health Statistics, 2007).

Maslov, K.

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef] [PubMed]

Nguyen, H. V.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Pang, Y.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Park, J. E.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Pasquale, L. R.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Pleis, J. R.

J. R. Pleis and J. W. Lucas, Summary Health Statistics for U.S. Adults: National Health Interview Survey (National Center for Health Statistics, 2007).

Puliafito, C. A.

Regillo, C. D.

B. R. Hurley and C. D. Regillo, in Retinal Angiography and Optical Coherence Tomography, J.Fernando Arevalo, ed. (Springer, 2009), pp. 27-42.
[CrossRef]

Shah, S. T.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Stoica, G.

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Thieme, H.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Wang, L. V.

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Wang, X.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Xie, X.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Xie, Z.

Zhang, H. F.

N. Engl. J. Med.

L. P. Aiello, R. L. Avery, P. G. Arrigg, B. A. Keyt, H. D. Jampel, S. T. Shah, L. R. Pasquale, H. Thieme, M. A. Iwamoto, J. E. Park, H. V. Nguyen, L. M. Aiello, N. Ferrara, and G. L. King, N. Engl. J. Med. 331, 1480 (1994).
[CrossRef] [PubMed]

Nat. Biotechnol.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef] [PubMed]

Opt. Lett.

Other

J. R. Pleis and J. W. Lucas, Summary Health Statistics for U.S. Adults: National Health Interview Survey (National Center for Health Statistics, 2007).

B. R. Hurley and C. D. Regillo, in Retinal Angiography and Optical Coherence Tomography, J.Fernando Arevalo, ed. (Springer, 2009), pp. 27-42.
[CrossRef]

American National Standards Institute Inc. (ANSI), ANSI Z136.1-2007: American National Standard for Safe Use of Lasers (ANSI, 2007).

Supplementary Material (1)

» Media 1: MOV (2800 KB)     

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Figures (3)

Fig. 1
Fig. 1

Schematic of the photoacoustic ophthalmic angiography system. The inset photograph shows the animal positioning: λ, wavelength; AO, acoustic-optical; ND, neutral density.

Fig. 2
Fig. 2

Label-free photoacoustic ophthalmic angiography of the iris microvasculature of a living adult Swiss Webster mouse. (a) Maximum amplitude projection image acquired at 570 nm (volumetric visualization is available online as Media 1). (b) Close-up of the boxed area in (a). The arrows indicate individual RBCs in iris capillaries. (c) Profile of RBC crossed by the dashed curve in (b). LIC, lesser iris circle; PA, photoacoustic signal.

Fig. 3
Fig. 3

Label-free photoacoustic ophthalmic angiography of hemoglobin oxygen saturation ( s O 2 ) in the iris microvasculature of a living adult Swiss Webster mouse. The imaged region is the same as that shown in Fig. 2a but with a focal plane closer to the posterior segment to better visualize the peripheral vascular structures. A dual-wavelength (570 and 578 nm) s O 2 measurement was performed on the boxed region of interest. A vessel-by-vessel s O 2 mapping was generated and overlaid on the maximum amplitude projection image acquired at 570 nm. CP, ciliary process; MIC, major iris circle; RCB, recurrent choroidal branch; RIA, radial iris artery.

Tables (1)

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Table 1 Experimental Parameters a

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