Abstract

We demonstrate that both oxyhemoglobin and deoxyhemoglobin have sequential two-color, two-photon absorption properties that can serve as endogenous contrasts in microvasculature imaging. Using a sensitive modulation transfer technique, we are able to image hemoglobin in red blood cells with micrometer resolution, both in vitro and in vivo. We show that excellent contrast from hemoglobin without any labeling can be obtained in tissue.

© 2007 Optical Society of America

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2007 (2)

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, L. Hong, J. D. Simon, and W. S. Warren, Proc. SPIE 6424, 642402 (2007).
[CrossRef]

G. O. Clay, C. B. Schaffer, and D. Kleinfeld, J. Chem. Phys. 126, 025102 (2007).
[CrossRef] [PubMed]

2006 (4)

V. P. Zharov, E. I. Galanzha, Y. Menyaev, and V. V. Tuchin, J. Biomed. Opt. 11, 054034 (2006).
[CrossRef] [PubMed]

A. R. Hilde, B. Mischa, M. V. Erik, B. S. Chris, and M. Michiel, J. Biomed. Opt. 11, 050502 (2006).
[CrossRef]

T. Ye, G. Yurtsever, M. Fischer, J. D. Simon, and W. S. Warren, Proc. SPIE 6089, 60891X (2006).
[CrossRef]

G. O. Clay, A. C. Millard, C. B. Schaffer, J. Aus-Der-Au, P. S. Tsai, J. A. Squier, and D. Kleinfeld, J. Opt. Soc. Am. B 23, 932 (2006).
[CrossRef]

2005 (4)

J. C. Miller, H. H. Pien, D. Sahani, A. G. Sorensen, and J. H. Thrall, J. Natl. Cancer Inst. 97, 172 (2005).
[CrossRef] [PubMed]

B. S. Sorg, B. J. Moeller, O. Donovan, Y. T. Cao, and M. W. Dewhirst, J. Biomed. Opt. 10, 044004 (2005).
[CrossRef]

M. C. Fischer, T. Ye, G. Yurtsever, A. Miller, M. Ciocca, W. Wagner, and W. S. Warren, Opt. Lett. 30, 1551 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, J. C. Lung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, Opt. Lett. 30, 2272 (2005).
[CrossRef] [PubMed]

2004 (1)

B. W. Pogue, S. D. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. M. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, J. Biomed. Opt. 9, 541 (2004).
[CrossRef] [PubMed]

2003 (3)

2002 (1)

2001 (1)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, Neuron 31, 903 (2001).
[CrossRef] [PubMed]

1999 (1)

1998 (2)

P. T. C. So, H. Kim, and I. E. Kochevar, Opt. Express 3, 339 (1998).
[CrossRef] [PubMed]

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, Proc. Natl. Acad. Sci. U.S.A. 95, 15741 (1998).
[CrossRef] [PubMed]

1986 (1)

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Appl. Opt. (1)

J. Biomed. Opt. (4)

V. P. Zharov, E. I. Galanzha, Y. Menyaev, and V. V. Tuchin, J. Biomed. Opt. 11, 054034 (2006).
[CrossRef] [PubMed]

B. S. Sorg, B. J. Moeller, O. Donovan, Y. T. Cao, and M. W. Dewhirst, J. Biomed. Opt. 10, 044004 (2005).
[CrossRef]

B. W. Pogue, S. D. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. M. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, J. Biomed. Opt. 9, 541 (2004).
[CrossRef] [PubMed]

A. R. Hilde, B. Mischa, M. V. Erik, B. S. Chris, and M. Michiel, J. Biomed. Opt. 11, 050502 (2006).
[CrossRef]

J. Cell. Biochem. (1)

P. C. Lin, J. Cell. Biochem. 90, 484 (2003).
[CrossRef] [PubMed]

J. Chem. Phys. (1)

G. O. Clay, C. B. Schaffer, and D. Kleinfeld, J. Chem. Phys. 126, 025102 (2007).
[CrossRef] [PubMed]

J. Natl. Cancer Inst. (1)

J. C. Miller, H. H. Pien, D. Sahani, A. G. Sorensen, and J. H. Thrall, J. Natl. Cancer Inst. 97, 172 (2005).
[CrossRef] [PubMed]

J. Opt. Soc. Am. B (1)

Nat. Med. (1)

D. M. McDonald and P. L. Choyke, Nat. Med. 9, 713 (2003).
[CrossRef] [PubMed]

Nature (1)

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Neuron (1)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, Neuron 31, 903 (2001).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (4)

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

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, Proc. Natl. Acad. Sci. U.S.A. 95, 15741 (1998).
[CrossRef] [PubMed]

Proc. SPIE (2)

T. Ye, G. Yurtsever, M. Fischer, J. D. Simon, and W. S. Warren, Proc. SPIE 6089, 60891X (2006).
[CrossRef]

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, L. Hong, J. D. Simon, and W. S. Warren, Proc. SPIE 6424, 642402 (2007).
[CrossRef]

Other (1)

G. Yurtsever, T. Ye, K. Weaver, and W. Warren, presented at the Biomedical Optics Topical Meeting, Fort Lauderdale, Fla., March 19-22, 2006.

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Figures (5)

Fig. 1
Fig. 1

Transient absorption signals of (a) R6G with 775 nm pump and 650 nm probe, (b) oxyhemoglobin (curve with solid circles) and deoxyhemoglobin (curve with solid squares), with 775 nm pump and 650 nm probe, and (c) oxyhemoglobin (curve with solid circles) and deoxyhemoglobin (curve with solid squares), with 650 nm pump and 775 nm probe.

Fig. 2
Fig. 2

(a) Bright field image and (b) laser scanning two-color TPA image of mouse RBCs. (c) The reconstructed 3D cell image is based on 10 layers with layer separation of 1 μ m with an image size of 40 μ m × 40 μ m × 10 μ m .

Fig. 3
Fig. 3

Bright field image (the black box represents the imaging area) and a series of laser scanning two-color TPA image at various depths in the black mouse ear. Pump is at 775 nm ( 5.1 mW ) and probe is at 650 nm ( 3.5 mW ) .

Fig. 4
Fig. 4

Bright field image and a series of laser scanning two-color TPA image at various depths in the black mouse ear. Pump is at 650 nm ( 2.4 mW ) , and probe is at 775 nm ( 1.4 mW ) .

Fig. 5
Fig. 5

Bright field image and a series of laser scanning two-color TPA image at various depths in the live nude mouse ear. Pump is at 775 nm ( 6.0 mW ) and probe is at 650 nm ( 4.0 mW ) .

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