Abstract

Due to strong light scattering in tissue, both the spatial resolution and maximum penetration depth of optical-resolution photoacoustic microscopy (OR-PAM) deteriorate sharply with depth. To reduce tissue scattering, we propose to use glycerol as an optical clearing agent in OR-PAM. Our results show that the imaging performance of OR-PAM can be greatly enhanced by optical clearing both in vitro and in vivo.

© 2013 Optical Society of America

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  2. Y. Zhou, C. Zhang, D.-K. Yao, and L. V. Wang, J. Biomed. Opt. 17, 126019 (2012).
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
  7. L. V. Wang and H. Wu, Biomedical Optics: Principles and Imaging (Wiley, 2007).
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  9. M. Kinnunen and R. Myllylä, J. Phys. D 382654 (2005).
    [CrossRef]
  10. R. Myllylä, Z. Zhao, and M. Kinnunen, in Handbook of Optical Sensing of Glucose in Biological Fluids and TissuesV. V. Tuchin, ed. (Taylor & Francis, 2008).
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    [CrossRef]
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    [CrossRef]
  13. G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, Photochem. Photobiol. 77541 (2003).
    [CrossRef]
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    [CrossRef]
  15. D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
    [CrossRef]
  16. J. Wang, R. Shi, and D. Zhu, J. Biomed. Opt. 18, 061209 (2013).
    [CrossRef]

2013 (1)

J. Wang, R. Shi, and D. Zhu, J. Biomed. Opt. 18, 061209 (2013).
[CrossRef]

2012 (2)

L. V. Wang and S. Hu, Science 335, 1458 (2012).
[CrossRef]

Y. Zhou, C. Zhang, D.-K. Yao, and L. V. Wang, J. Biomed. Opt. 17, 126019 (2012).
[CrossRef]

2011 (2)

J. Yao and L. V. Wang, Contrast Media Mol. Imag. 6, 332 (2011).
[CrossRef]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, J. Biomed. Opt. 16, 076003 (2011).
[CrossRef]

2010 (4)

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, J. Biophoton. 3, 44 (2010).
[CrossRef]

J. Yao, K. I. Maslov, Y. Shi, L. A. Taber, and L. V. Wang, Opt. Lett. 35, 1419 (2010).
[CrossRef]

S. L. Chen, T. Ling, S. W. Huang, H. Won Baac, and L. J. Guo, Opt. Lett. 35, 1200 (2010).
[CrossRef]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
[CrossRef]

2008 (1)

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

2005 (2)

M. Kinnunen and R. Myllylä, J. Phys. D 382654 (2005).
[CrossRef]

V. V. Tuchin, J. Phys. D 38, 2497 (2005).
[CrossRef]

2003 (1)

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, Photochem. Photobiol. 77541 (2003).
[CrossRef]

Chen, S. L.

Cui, H.

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

Dozier, S. S.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, Photochem. Photobiol. 77541 (2003).
[CrossRef]

Guo, L. J.

Han, Z.

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, J. Biophoton. 3, 44 (2010).
[CrossRef]

Hu, S.

L. V. Wang and S. Hu, Science 335, 1458 (2012).
[CrossRef]

Huang, S. W.

Kinnunen, M.

M. Kinnunen and R. Myllylä, J. Phys. D 382654 (2005).
[CrossRef]

R. Myllylä, Z. Zhao, and M. Kinnunen, in Handbook of Optical Sensing of Glucose in Biological Fluids and TissuesV. V. Tuchin, ed. (Taylor & Francis, 2008).

Larin, K. V.

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, Laser & Photon. Rev. (2013) .
[CrossRef]

Li, P.

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

Ling, T.

Luo, Q.

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
[CrossRef]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, Laser & Photon. Rev. (2013) .
[CrossRef]

Mao, Z.

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, J. Biophoton. 3, 44 (2010).
[CrossRef]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

Maslov, K. I.

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, J. Biomed. Opt. 16, 076003 (2011).
[CrossRef]

J. Yao, K. I. Maslov, Y. Shi, L. A. Taber, and L. V. Wang, Opt. Lett. 35, 1419 (2010).
[CrossRef]

Myllylä, R.

M. Kinnunen and R. Myllylä, J. Phys. D 382654 (2005).
[CrossRef]

R. Myllylä, Z. Zhao, and M. Kinnunen, in Handbook of Optical Sensing of Glucose in Biological Fluids and TissuesV. V. Tuchin, ed. (Taylor & Francis, 2008).

Readinger, A.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, Photochem. Photobiol. 77541 (2003).
[CrossRef]

Shi, R.

J. Wang, R. Shi, and D. Zhu, J. Biomed. Opt. 18, 061209 (2013).
[CrossRef]

Shi, Y.

Taber, L. A.

Tuchin, V. V.

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, J. Biophoton. 3, 44 (2010).
[CrossRef]

V. V. Tuchin, J. Phys. D 38, 2497 (2005).
[CrossRef]

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, Laser & Photon. Rev. (2013) .
[CrossRef]

Vargas, G.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, Photochem. Photobiol. 77541 (2003).
[CrossRef]

Wang, J.

J. Wang, R. Shi, and D. Zhu, J. Biomed. Opt. 18, 061209 (2013).
[CrossRef]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
[CrossRef]

Wang, L. V.

L. V. Wang and S. Hu, Science 335, 1458 (2012).
[CrossRef]

Y. Zhou, C. Zhang, D.-K. Yao, and L. V. Wang, J. Biomed. Opt. 17, 126019 (2012).
[CrossRef]

J. Yao and L. V. Wang, Contrast Media Mol. Imag. 6, 332 (2011).
[CrossRef]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, J. Biomed. Opt. 16, 076003 (2011).
[CrossRef]

J. Yao, K. I. Maslov, Y. Shi, L. A. Taber, and L. V. Wang, Opt. Lett. 35, 1419 (2010).
[CrossRef]

L. V. Wang and H. Wu, Biomedical Optics: Principles and Imaging (Wiley, 2007).

Welch, A. J.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, Photochem. Photobiol. 77541 (2003).
[CrossRef]

Wen, X.

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, J. Biophoton. 3, 44 (2010).
[CrossRef]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
[CrossRef]

Won Baac, H.

Wu, H.

L. V. Wang and H. Wu, Biomedical Optics: Principles and Imaging (Wiley, 2007).

Xia, Y.

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, J. Biomed. Opt. 16, 076003 (2011).
[CrossRef]

Yao, D.-K.

Y. Zhou, C. Zhang, D.-K. Yao, and L. V. Wang, J. Biomed. Opt. 17, 126019 (2012).
[CrossRef]

Yao, J.

J. Yao and L. V. Wang, Contrast Media Mol. Imag. 6, 332 (2011).
[CrossRef]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, J. Biomed. Opt. 16, 076003 (2011).
[CrossRef]

J. Yao, K. I. Maslov, Y. Shi, L. A. Taber, and L. V. Wang, Opt. Lett. 35, 1419 (2010).
[CrossRef]

Zhang, C.

Y. Zhou, C. Zhang, D.-K. Yao, and L. V. Wang, J. Biomed. Opt. 17, 126019 (2012).
[CrossRef]

Zhang, J.

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

Zhang, Y.

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, J. Biomed. Opt. 16, 076003 (2011).
[CrossRef]

Zhao, Z.

R. Myllylä, Z. Zhao, and M. Kinnunen, in Handbook of Optical Sensing of Glucose in Biological Fluids and TissuesV. V. Tuchin, ed. (Taylor & Francis, 2008).

Zhi, Z.

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
[CrossRef]

Zhou, Y.

Y. Zhou, C. Zhang, D.-K. Yao, and L. V. Wang, J. Biomed. Opt. 17, 126019 (2012).
[CrossRef]

Zhu, D.

J. Wang, R. Shi, and D. Zhu, J. Biomed. Opt. 18, 061209 (2013).
[CrossRef]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
[CrossRef]

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, J. Biophoton. 3, 44 (2010).
[CrossRef]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, Laser & Photon. Rev. (2013) .
[CrossRef]

Contrast Media Mol. Imag. (1)

J. Yao and L. V. Wang, Contrast Media Mol. Imag. 6, 332 (2011).
[CrossRef]

J. Biomed. Opt. (5)

Y. Zhou, C. Zhang, D.-K. Yao, and L. V. Wang, J. Biomed. Opt. 17, 126019 (2012).
[CrossRef]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, J. Biomed. Opt. 16, 076003 (2011).
[CrossRef]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, J. Biomed. Opt. 13, 021106 (2008).
[CrossRef]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, J. Biomed. Opt. 15, 026008 (2010).
[CrossRef]

J. Wang, R. Shi, and D. Zhu, J. Biomed. Opt. 18, 061209 (2013).
[CrossRef]

J. Biophoton. (1)

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, J. Biophoton. 3, 44 (2010).
[CrossRef]

J. Phys. D (2)

V. V. Tuchin, J. Phys. D 38, 2497 (2005).
[CrossRef]

M. Kinnunen and R. Myllylä, J. Phys. D 382654 (2005).
[CrossRef]

Opt. Lett. (2)

Photochem. Photobiol. (1)

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, Photochem. Photobiol. 77541 (2003).
[CrossRef]

Science (1)

L. V. Wang and S. Hu, Science 335, 1458 (2012).
[CrossRef]

Other (3)

R. Myllylä, Z. Zhao, and M. Kinnunen, in Handbook of Optical Sensing of Glucose in Biological Fluids and TissuesV. V. Tuchin, ed. (Taylor & Francis, 2008).

L. V. Wang and H. Wu, Biomedical Optics: Principles and Imaging (Wiley, 2007).

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, Laser & Photon. Rev. (2013) .
[CrossRef]

Supplementary Material (2)

» Media 1: MPG (3801 KB)     
» Media 2: MPG (3801 KB)     

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Figures (5)

Fig. 1.
Fig. 1.

System schematic used in the experiment. CorL, correction lens; OL, objective lens; RAP, right-angle prism; RhP, rhomboid prism; SOL, silicone oil layer; UT, ultrasonic transducer.

Fig. 2.
Fig. 2.

Optical clearing-aided PAM of a coin covered by mouse skin. (a) Photograph of the one cent coin used in the experiment. (b)–(d) PA images of the coin at different times during optical clearing. (e) Time course of the PA amplitude averaged over the whole image during optical clearing. The higher PA amplitude indicates that the optical clearing increased penetration depth.

Fig. 3.
Fig. 3.

In vivo PAM of mouse scalp facilitated by optical clearing. (a) PAM image before optical clearing. (b) PAM image with capillaries after optical clearing. (c) PAM image with parts of capillary layer digitally removed after optical clearing. (d)–(f) PA amplitude along the red dashed line in (a)–(c). MAP image along the y axis (g) before and (h) after optical clearing. (i) PA amplitude averaged along the x direction of (g) (blue line) and (h) (red dashed line). 3D PA image (j) (Media 1) before and (k) (Media 2) after optical clearing.

Fig. 4.
Fig. 4.

Optical clearing reveals more capillaries. (a) and (b) Close-ups of PAM images in the red dashed boxes in Figs. 3(a) and 3(b). (c) and (d) PA amplitudes along the red dashed lines in (a) and (b).

Fig. 5.
Fig. 5.

Optical clearing improves the lateral resolution for deep vessels. (a) Close-up of PAM image in the green dashed box in Fig. 3(a). (b) Close-up of PAM image in the green dashed box in Fig. 3(c). (c) and (d) PA amplitudes along the red dashed lines in (a) and (b). (e) Combined curves in (c) and (d) after normalization.

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