Abstract

Acoustic resolution photoacoustic microscopy (AR-PAM) takes advantage of weak acoustic scattering to image fine structures, such as the subcutaneous microvasculature, providing a spatial resolution on the order of tens of micrometers. However, the amplitude of AR-PAM deteriorates sharply with depth, as a result of light scattering and acoustic attenuation caused by structures such as the skin. Optical clearing techniques can enhance optical transmittance by decreasing the scattering of light through tissues. However, it is unknown whether optical clearing agents (OCAs) can be used to improve AR-PAM. We applied different types of OCAs to rat dorsal skin in an ex vivo study to determine the effects of OCAs on photoacoustic detection. We identified three OCAs that improved the photoacoustic amplitude for further in vivo testing. With the use of an appropriate penetration enhancer, PEG-400 significantly improved the photoacoustic amplitude for detection of deep-sealed blood vessels, while glycerol alone improved the image quality of shallow vessels. In contrast, DMSO application resulted in decreased photoacoustic amplitude in the in vivo trials.

© 2013 Optical Society of America

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  1. I. M. Braverman, J. Invest. Dermatol. 5, 3 (2000).
    [CrossRef]
  2. G. E. Koehl, A. Gaumann, and E. K. Geissler, Clin. Exp. Metastasis 26, 329 (2009).
    [CrossRef]
  3. H. F. Zhang, K. Maslov, and L. H. Wang, Nat. Protoc. 2, 797 (2007).
    [CrossRef]
  4. K. Maslov, G. Stoica, and L. H. Wang, Opt. Lett. 30, 625 (2005).
    [CrossRef]
  5. V. V. Tuchin, J. Phys. D 38, 2497 (2005).
    [CrossRef]
  6. J. Wang, D. Zhu, M. Chen, and X. J. Liu, J. Innov. Opt. Health Sci. 3, 159 (2010).
    [CrossRef]
  7. S. G. Proskurin and I. V. Meglinski, Laser Phys. Lett. 4, 824 (2007).
    [CrossRef]
  8. R. Cicchi, F. S. Pavone, D. Massi, and D. D. Sampson, Opt. Express 13, 2337 (2005).
    [CrossRef]
  9. Y. Zhou, J. J. Yao, and L. H. Wang, Opt. Lett. 38, 2592 (2013).
    [CrossRef]
  10. X. Q. Yang, X. Cai, K. Maslov, L. H. Wang, and Q. M. Luo, Chin. Opt. Lett. 8, 609 (2010).
    [CrossRef]
  11. X. Wen, Z. Z. Mao, Z. Z. Han, V. V. Tuchin, and D. Zhu, J. Biophotonics 3, 44 (2010).
    [CrossRef]
  12. M. Zimmerley, R. A. McClure, B. Choi, and E. O. Potma, Appl. Opt. 48, D79 (2009).
    [CrossRef]
  13. L. Pan, L. Zan, and F. S. Foster, Ultrasound Med. Biol. 24, 995 (1998).
    [CrossRef]
  14. R. Feng, Ultrasonics Handbook (Nanjing University, 1999).
  15. D. Zhu, J. Wang, Z. W. Zhi, X. Wen, and Q. M. Luo, J. Biomed. Opt. 15, 026008 (2010).
    [CrossRef]
  16. G. Vargas, J. K. Barton, and A. J. Welch, J. Biomed. Opt. 13, 021114 (2008).
    [CrossRef]
  17. T. Agner and J. Serup, Clin. Exp. Dermatol. 14, 214 (1989).
    [CrossRef]
  18. M. Kinnunen and R. Myllylä, J. Phys. D 38, 2654 (2005).
    [CrossRef]
  19. Z. M. Zhao and R. Myllylä, Proc. SPIE 4707, 153 (2002).
    [CrossRef]
  20. C. C. Harland, J. C. Bamber, B. A. Gusterson, and P. S. Mortime, Br. J. Dermatol. 128, 525 (1993).
    [CrossRef]

2013

2010

X. Q. Yang, X. Cai, K. Maslov, L. H. Wang, and Q. M. Luo, Chin. Opt. Lett. 8, 609 (2010).
[CrossRef]

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

J. Wang, D. Zhu, M. Chen, and X. J. Liu, J. Innov. Opt. Health Sci. 3, 159 (2010).
[CrossRef]

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

2009

M. Zimmerley, R. A. McClure, B. Choi, and E. O. Potma, Appl. Opt. 48, D79 (2009).
[CrossRef]

G. E. Koehl, A. Gaumann, and E. K. Geissler, Clin. Exp. Metastasis 26, 329 (2009).
[CrossRef]

2008

G. Vargas, J. K. Barton, and A. J. Welch, J. Biomed. Opt. 13, 021114 (2008).
[CrossRef]

2007

S. G. Proskurin and I. V. Meglinski, Laser Phys. Lett. 4, 824 (2007).
[CrossRef]

H. F. Zhang, K. Maslov, and L. H. Wang, Nat. Protoc. 2, 797 (2007).
[CrossRef]

2005

2002

Z. M. Zhao and R. Myllylä, Proc. SPIE 4707, 153 (2002).
[CrossRef]

2000

I. M. Braverman, J. Invest. Dermatol. 5, 3 (2000).
[CrossRef]

1998

L. Pan, L. Zan, and F. S. Foster, Ultrasound Med. Biol. 24, 995 (1998).
[CrossRef]

1993

C. C. Harland, J. C. Bamber, B. A. Gusterson, and P. S. Mortime, Br. J. Dermatol. 128, 525 (1993).
[CrossRef]

1989

T. Agner and J. Serup, Clin. Exp. Dermatol. 14, 214 (1989).
[CrossRef]

Agner, T.

T. Agner and J. Serup, Clin. Exp. Dermatol. 14, 214 (1989).
[CrossRef]

Bamber, J. C.

C. C. Harland, J. C. Bamber, B. A. Gusterson, and P. S. Mortime, Br. J. Dermatol. 128, 525 (1993).
[CrossRef]

Barton, J. K.

G. Vargas, J. K. Barton, and A. J. Welch, J. Biomed. Opt. 13, 021114 (2008).
[CrossRef]

Braverman, I. M.

I. M. Braverman, J. Invest. Dermatol. 5, 3 (2000).
[CrossRef]

Cai, X.

Chen, M.

J. Wang, D. Zhu, M. Chen, and X. J. Liu, J. Innov. Opt. Health Sci. 3, 159 (2010).
[CrossRef]

Choi, B.

Cicchi, R.

Feng, R.

R. Feng, Ultrasonics Handbook (Nanjing University, 1999).

Foster, F. S.

L. Pan, L. Zan, and F. S. Foster, Ultrasound Med. Biol. 24, 995 (1998).
[CrossRef]

Gaumann, A.

G. E. Koehl, A. Gaumann, and E. K. Geissler, Clin. Exp. Metastasis 26, 329 (2009).
[CrossRef]

Geissler, E. K.

G. E. Koehl, A. Gaumann, and E. K. Geissler, Clin. Exp. Metastasis 26, 329 (2009).
[CrossRef]

Gusterson, B. A.

C. C. Harland, J. C. Bamber, B. A. Gusterson, and P. S. Mortime, Br. J. Dermatol. 128, 525 (1993).
[CrossRef]

Han, Z. Z.

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

Harland, C. C.

C. C. Harland, J. C. Bamber, B. A. Gusterson, and P. S. Mortime, Br. J. Dermatol. 128, 525 (1993).
[CrossRef]

Kinnunen, M.

M. Kinnunen and R. Myllylä, J. Phys. D 38, 2654 (2005).
[CrossRef]

Koehl, G. E.

G. E. Koehl, A. Gaumann, and E. K. Geissler, Clin. Exp. Metastasis 26, 329 (2009).
[CrossRef]

Liu, X. J.

J. Wang, D. Zhu, M. Chen, and X. J. Liu, J. Innov. Opt. Health Sci. 3, 159 (2010).
[CrossRef]

Luo, Q. M.

X. Q. Yang, X. Cai, K. Maslov, L. H. Wang, and Q. M. Luo, Chin. Opt. Lett. 8, 609 (2010).
[CrossRef]

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

Mao, Z. Z.

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

Maslov, K.

Massi, D.

McClure, R. A.

Meglinski, I. V.

S. G. Proskurin and I. V. Meglinski, Laser Phys. Lett. 4, 824 (2007).
[CrossRef]

Mortime, P. S.

C. C. Harland, J. C. Bamber, B. A. Gusterson, and P. S. Mortime, Br. J. Dermatol. 128, 525 (1993).
[CrossRef]

Myllylä, R.

M. Kinnunen and R. Myllylä, J. Phys. D 38, 2654 (2005).
[CrossRef]

Z. M. Zhao and R. Myllylä, Proc. SPIE 4707, 153 (2002).
[CrossRef]

Pan, L.

L. Pan, L. Zan, and F. S. Foster, Ultrasound Med. Biol. 24, 995 (1998).
[CrossRef]

Pavone, F. S.

Potma, E. O.

Proskurin, S. G.

S. G. Proskurin and I. V. Meglinski, Laser Phys. Lett. 4, 824 (2007).
[CrossRef]

Sampson, D. D.

Serup, J.

T. Agner and J. Serup, Clin. Exp. Dermatol. 14, 214 (1989).
[CrossRef]

Stoica, G.

Tuchin, V. V.

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

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

Vargas, G.

G. Vargas, J. K. Barton, and A. J. Welch, J. Biomed. Opt. 13, 021114 (2008).
[CrossRef]

Wang, J.

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

J. Wang, D. Zhu, M. Chen, and X. J. Liu, J. Innov. Opt. Health Sci. 3, 159 (2010).
[CrossRef]

Wang, L. H.

Welch, A. J.

G. Vargas, J. K. Barton, and A. J. Welch, J. Biomed. Opt. 13, 021114 (2008).
[CrossRef]

Wen, X.

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

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

Yang, X. Q.

Yao, J. J.

Zan, L.

L. Pan, L. Zan, and F. S. Foster, Ultrasound Med. Biol. 24, 995 (1998).
[CrossRef]

Zhang, H. F.

H. F. Zhang, K. Maslov, and L. H. Wang, Nat. Protoc. 2, 797 (2007).
[CrossRef]

Zhao, Z. M.

Z. M. Zhao and R. Myllylä, Proc. SPIE 4707, 153 (2002).
[CrossRef]

Zhi, Z. W.

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

Zhou, Y.

Zhu, D.

J. Wang, D. Zhu, M. Chen, and X. J. Liu, J. Innov. Opt. Health Sci. 3, 159 (2010).
[CrossRef]

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

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

Zimmerley, M.

Appl. Opt.

Br. J. Dermatol.

C. C. Harland, J. C. Bamber, B. A. Gusterson, and P. S. Mortime, Br. J. Dermatol. 128, 525 (1993).
[CrossRef]

Chin. Opt. Lett.

Clin. Exp. Dermatol.

T. Agner and J. Serup, Clin. Exp. Dermatol. 14, 214 (1989).
[CrossRef]

Clin. Exp. Metastasis

G. E. Koehl, A. Gaumann, and E. K. Geissler, Clin. Exp. Metastasis 26, 329 (2009).
[CrossRef]

J. Biomed. Opt.

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

G. Vargas, J. K. Barton, and A. J. Welch, J. Biomed. Opt. 13, 021114 (2008).
[CrossRef]

J. Biophotonics

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

J. Innov. Opt. Health Sci.

J. Wang, D. Zhu, M. Chen, and X. J. Liu, J. Innov. Opt. Health Sci. 3, 159 (2010).
[CrossRef]

J. Invest. Dermatol.

I. M. Braverman, J. Invest. Dermatol. 5, 3 (2000).
[CrossRef]

J. Phys. D

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

M. Kinnunen and R. Myllylä, J. Phys. D 38, 2654 (2005).
[CrossRef]

Laser Phys. Lett.

S. G. Proskurin and I. V. Meglinski, Laser Phys. Lett. 4, 824 (2007).
[CrossRef]

Nat. Protoc.

H. F. Zhang, K. Maslov, and L. H. Wang, Nat. Protoc. 2, 797 (2007).
[CrossRef]

Opt. Express

Opt. Lett.

Proc. SPIE

Z. M. Zhao and R. Myllylä, Proc. SPIE 4707, 153 (2002).
[CrossRef]

Ultrasound Med. Biol.

L. Pan, L. Zan, and F. S. Foster, Ultrasound Med. Biol. 24, 995 (1998).
[CrossRef]

Other

R. Feng, Ultrasonics Handbook (Nanjing University, 1999).

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Figures (6)

Fig. 1.
Fig. 1.

(a) Schematic of the imaging head. (b) Diagram of the sample setup. A, absorber; CL, conical lens; MP, metal plate; OC, optical condenser; S, sample; SH, sample holder; U, ultrasonic transducer; WT, water tank.

Fig. 2.
Fig. 2.

Changes in the photoacoustic amplitude with different OCAs (mean±SEM). Not all OCAs enhanced the amplitude. The enhancement was not monotonic.

Fig. 3.
Fig. 3.

Changes in photoacoustic spatial resolution with different OCAs (mean±SEM). No significant changes were observed except for glycerol.

Fig. 4.
Fig. 4.

Comparative images and statistical analysis for in vivo imaging with a mixture of PEG-400 and thiazone. (a) and (b) are photographs of skin before and after immersion. (c) and (d) are photoacoustic maximum amplitude projection (MAP) images projected along the depth direction. (e) and (f) are B-scan images denoted by the dashed lines in (c) and (d). The horizontal axis is the scan direction, and the vertical axis is the depth. (g) shows transverse plots of the vessel indicated by the green arrows in (c) and (d). (h) shows the statistical results for 10 randomly selected vessels. The scale bar is the same for (a)–(f).

Fig. 5.
Fig. 5.

Comparative images and statistical analysis for in vivo imaging with glycerol. The descriptions of the subgraphs are the same as in Fig. 4.

Fig. 6.
Fig. 6.

Comparative images and statistical analysis for in vivo imaging with DMSO. The descriptions of the subgraphs are the same as in Fig. 4.

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