Abstract

Imaging of cell nuclei plays a critical role in cancer diagnosis and prognosis. To image noninvasively cell nuclei in vivo without staining, we developed UV photoacoustic microscopy (UV-PAM), in which 266nm wavelength UV light excites unlabeled DNA and RNA in cell nuclei to produce photoacoustic waves. We applied UV-PAM to ex vivo imaging of cell nuclei in a mouse lip and a mouse small intestine and to in vivo imaging of the cell nuclei in the mouse skin. The UV-PAM images of unstained cell nuclei match the optical micrographs of the histologically stained cell nuclei. Given intrinsic optical contrast and high spatial resolution, in vivo label-free UV-PAM has potential for unique biological and clinical application.

© 2010 Optical Society of America

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References

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2010 (1)

S. Hu and L. V. Wang, J. Biomed. Opt. 15, 011101 (2010).
[CrossRef] [PubMed]

2009 (3)

S. Kaeb, M. Landthaler, and U. Hohenleutner, Lasers Med. Sci. 24, 819 (2009).
[CrossRef] [PubMed]

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

L. V. Wang, Nat. Photon. 3, 503 (2009).
[CrossRef]

2008 (2)

J. Paoli, M. Smedh, A. M. Wennberg, and M. B. Ericson, J. Invest. Dermatol. 128, 1248 (2008).
[CrossRef]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Proc. SPIE 6856, 68561I (2008).
[CrossRef]

2004 (1)

D. Zink, A. H. Fischer, and J. A. Nickerson, Nat. Rev. Cancer 4, 677 (2004).
[CrossRef] [PubMed]

1996 (1)

J. McHowat, J. H. Jones, and M. H. Creer, J. Lipid Res. 37, 2450 (1996).
[PubMed]

1990 (1)

C. M. Stoscheck, Methods Enzymol. 182, 50 (1990).
[CrossRef] [PubMed]

Creer, M. H.

J. McHowat, J. H. Jones, and M. H. Creer, J. Lipid Res. 37, 2450 (1996).
[PubMed]

Dusza, S. W.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

Ericson, M. B.

J. Paoli, M. Smedh, A. M. Wennberg, and M. B. Ericson, J. Invest. Dermatol. 128, 1248 (2008).
[CrossRef]

Fischer, A. H.

D. Zink, A. H. Fischer, and J. A. Nickerson, Nat. Rev. Cancer 4, 677 (2004).
[CrossRef] [PubMed]

Gareau, D. S.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

Hohenleutner, U.

S. Kaeb, M. Landthaler, and U. Hohenleutner, Lasers Med. Sci. 24, 819 (2009).
[CrossRef] [PubMed]

Hu, S.

S. Hu and L. V. Wang, J. Biomed. Opt. 15, 011101 (2010).
[CrossRef] [PubMed]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Proc. SPIE 6856, 68561I (2008).
[CrossRef]

Jones, J. H.

J. McHowat, J. H. Jones, and M. H. Creer, J. Lipid Res. 37, 2450 (1996).
[PubMed]

Kaeb, S.

S. Kaeb, M. Landthaler, and U. Hohenleutner, Lasers Med. Sci. 24, 819 (2009).
[CrossRef] [PubMed]

Karen, J. K.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

Landthaler, M.

S. Kaeb, M. Landthaler, and U. Hohenleutner, Lasers Med. Sci. 24, 819 (2009).
[CrossRef] [PubMed]

Maslov, K.

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Proc. SPIE 6856, 68561I (2008).
[CrossRef]

McHowat, J.

J. McHowat, J. H. Jones, and M. H. Creer, J. Lipid Res. 37, 2450 (1996).
[PubMed]

Molavi, D. W.

D. W. Molavi, The Practice of Surgical Pathology: A Beginner’s Guide to the Diagnostic Process (Springer, 2008).
[CrossRef]

Nehal, K. S.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

Nickerson, J. A.

D. Zink, A. H. Fischer, and J. A. Nickerson, Nat. Rev. Cancer 4, 677 (2004).
[CrossRef] [PubMed]

Paoli, J.

J. Paoli, M. Smedh, A. M. Wennberg, and M. B. Ericson, J. Invest. Dermatol. 128, 1248 (2008).
[CrossRef]

Rajadhyaksha, M.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

Smedh, M.

J. Paoli, M. Smedh, A. M. Wennberg, and M. B. Ericson, J. Invest. Dermatol. 128, 1248 (2008).
[CrossRef]

Stoscheck, C. M.

C. M. Stoscheck, Methods Enzymol. 182, 50 (1990).
[CrossRef] [PubMed]

Tudisco, M.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

Wang, L. V.

S. Hu and L. V. Wang, J. Biomed. Opt. 15, 011101 (2010).
[CrossRef] [PubMed]

L. V. Wang, Nat. Photon. 3, 503 (2009).
[CrossRef]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Proc. SPIE 6856, 68561I (2008).
[CrossRef]

Wennberg, A. M.

J. Paoli, M. Smedh, A. M. Wennberg, and M. B. Ericson, J. Invest. Dermatol. 128, 1248 (2008).
[CrossRef]

Zhang, H. F.

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Proc. SPIE 6856, 68561I (2008).
[CrossRef]

Zink, D.

D. Zink, A. H. Fischer, and J. A. Nickerson, Nat. Rev. Cancer 4, 677 (2004).
[CrossRef] [PubMed]

Br. J. Dermatol. (1)

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, Br. J. Dermatol. 160, 1242(2009).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

S. Hu and L. V. Wang, J. Biomed. Opt. 15, 011101 (2010).
[CrossRef] [PubMed]

J. Invest. Dermatol. (1)

J. Paoli, M. Smedh, A. M. Wennberg, and M. B. Ericson, J. Invest. Dermatol. 128, 1248 (2008).
[CrossRef]

J. Lipid Res. (1)

J. McHowat, J. H. Jones, and M. H. Creer, J. Lipid Res. 37, 2450 (1996).
[PubMed]

Lasers Med. Sci. (1)

S. Kaeb, M. Landthaler, and U. Hohenleutner, Lasers Med. Sci. 24, 819 (2009).
[CrossRef] [PubMed]

Methods Enzymol. (1)

C. M. Stoscheck, Methods Enzymol. 182, 50 (1990).
[CrossRef] [PubMed]

Nat. Photon. (1)

L. V. Wang, Nat. Photon. 3, 503 (2009).
[CrossRef]

Nat. Rev. Cancer (1)

D. Zink, A. H. Fischer, and J. A. Nickerson, Nat. Rev. Cancer 4, 677 (2004).
[CrossRef] [PubMed]

Proc. SPIE (1)

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Proc. SPIE 6856, 68561I (2008).
[CrossRef]

Other (1)

D. W. Molavi, The Practice of Surgical Pathology: A Beginner’s Guide to the Diagnostic Process (Springer, 2008).
[CrossRef]

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Figures (3)

Fig. 1
Fig. 1

Schematic of the UV-PAM system.

Fig. 2
Fig. 2

Cell-nuclear images of a 6-μm-thick cross section of mouse small intestine acquired with UV-PAM and histology. (a) Photoacoustic image (MAP) of the section without staining. (b) Histologic image of the section stained with hematoxylin and eosin. (c) Close-up of the area enclosed by dashed lines in (a). (d) Histologic image of the stained section enclosed by dashed lines in (b). The correlation coefficients are 0.88 between the images shown in panels (a) and (b) and 0.83 between the images shown in panels (c) and (d). PA, photoacoustic.

Fig. 3
Fig. 3

Cell-nuclear images of ex vivo and in vivo tissue acquired with UV-PAM. (a) Photoacoustic image (MAP) of epithelial cells in the ex vivo lip of a mouse. (b) Photoacoustic image (MAP) of epithelial cells in the ex vivo intestinal villi of a mouse. (c) In vivo photoacoustic images (dimensions: 250 μm × 250 μm ) of cells in the ear skin of a nude mouse at different depths (0, 53, and 105 μm ). PA, photoacoustic.

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