Abstract

We developed a new reflection-mode optical-resolution photoacoustic microscopy (OR-PAM) based on the cooperation of a reflective objective and an ultrasonic transducer. The reflective objective is used to produce nearly diffraction-limited optical focusing, and the excited ultrasound waves are then directly detected by an ultrasonic transducer that was placed in the central cone of the objective. This new design avoids the coupling between optical focusing and ultrasound transmission in the reflection mode. Moreover, the proposed system is able to provide lateral resolution of 1.2 μm at 580 nm, penetration depth of 0.9 mm in biological tissues, and a work distance of 6.0 mm. We present in vivo imaging of the microvasculature in mouse ears and in vitro imaging of red blood cells (RBCs), which demonstrate the capability of the system to study microcirculation.

© 2013 Optical Society of America

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  1. L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science335(6075), 1458–1462 (2012).
    [CrossRef] [PubMed]
  2. S. Hu and L. V. Wang, “Photoacoustic imaging and characterization of the microvasculature,” J. Biomed. Opt.15(1), 011101 (2010).
    [CrossRef] [PubMed]
  3. L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics3(9), 503–509 (2009).
    [CrossRef] [PubMed]
  4. H. Wang, D. Xing, and L. Z. Xiang, “Photoacoustic imaging using an ultrasonic Fresnel zone plate transducer,” J. Phys. D Appl. Phys.41(9), 095111 (2008).
    [CrossRef]
  5. H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol.24(7), 848–851 (2006).
    [CrossRef] [PubMed]
  6. H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
    [CrossRef] [PubMed]
  7. X. Q. Yang, X. Cai, K. Maslov, L. V. Wang, and Q. M. Luo, “High-resolution photoacoustic microscope for rat brain imaging in vivo,” Chin. Opt. Lett.8(6), 609–611 (2010).
    [CrossRef]
  8. K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett.33(9), 929–931 (2008).
    [CrossRef] [PubMed]
  9. Y. Liu, C. Zhang, and L. V. Wang, “Effects of light scattering on optical-resolution photoacoustic microscopy,” J. Biomed. Opt.17(12), 126014 (2012).
    [CrossRef] [PubMed]
  10. S. Hu, K. Maslov, and L. V. Wang, “Second-generation optical-resolution photoacoustic microscopy with improved sensitivity and speed,” Opt. Lett.36(7), 1134–1136 (2011).
    [CrossRef] [PubMed]
  11. G. Ku, K. Maslov, L. Li, and L. V. Wang, “Photoacoustic microscopy with 2-microm transverse resolution,” J. Biomed. Opt.15(2), 021302 (2010).
    [CrossRef] [PubMed]
  12. Z. Xie, S. Jiao, H. F. Zhang, and C. A. Puliafito, “Laser-scanning optical-resolution photoacoustic microscopy,” Opt. Lett.34(12), 1771–1773 (2009).
    [CrossRef] [PubMed]
  13. J. Yao, K. I. Maslov, E. R. Puckett, K. J. Rowland, B. W. Warner, and L. V. Wang, “Double-illumination photoacoustic microscopy,” Opt. Lett.37(4), 659–661 (2012).
    [CrossRef] [PubMed]
  14. C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
    [CrossRef] [PubMed]
  15. P. Hajireza, W. Shi, and R. J. Zemp, “Real-time handheld optical-resolution photoacoustic microscopy,” Opt. Express19(21), 20097–20102 (2011).
    [CrossRef] [PubMed]
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    [CrossRef]
  17. D. K. Yao, K. Maslov, K. K. Shung, Q. Zhou, and L. V. Wang, “In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA,” Opt. Lett.35(24), 4139–4141 (2010).
    [CrossRef] [PubMed]
  18. S. Hu, K. Maslov, V. Tsytsarev, and L. V. Wang, “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy,” J. Biomed. Opt.14(4), 040503 (2009).
    [CrossRef] [PubMed]
  19. J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
    [CrossRef] [PubMed]
  20. Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
    [CrossRef] [PubMed]
  21. V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
    [CrossRef] [PubMed]
  22. A. Krumholz, L. Wang, J. Yao, and L. V. Wang, “Functional photoacoustic microscopy of diabetic vasculature,” J. Biomed. Opt.17(6), 060502 (2012).
    [CrossRef] [PubMed]
  23. J. Yao and L. V. Wang, “Transverse flow imaging based on photoacoustic Doppler bandwidth broadening,” J. Biomed. Opt.15(2), 021304 (2010).
    [CrossRef] [PubMed]
  24. B. Rao, L. Li, K. Maslov, and L. Wang, “Hybrid-scanning optical-resolution photoacoustic microscopy for in vivo vasculature imaging,” Opt. Lett.35(10), 1521–1523 (2010).
    [CrossRef] [PubMed]
  25. J. M. Boone and J. A. Seibert, “An analytical edge spread function model for computer fitting and subsequent calculation of the LSF and MTF,” Med. Phys.21(10), 1541–1545 (1994).
    [CrossRef] [PubMed]

2013 (1)

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

2012 (7)

A. Krumholz, L. Wang, J. Yao, and L. V. Wang, “Functional photoacoustic microscopy of diabetic vasculature,” J. Biomed. Opt.17(6), 060502 (2012).
[CrossRef] [PubMed]

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science335(6075), 1458–1462 (2012).
[CrossRef] [PubMed]

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
[CrossRef] [PubMed]

Y. Liu, C. Zhang, and L. V. Wang, “Effects of light scattering on optical-resolution photoacoustic microscopy,” J. Biomed. Opt.17(12), 126014 (2012).
[CrossRef] [PubMed]

C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
[CrossRef] [PubMed]

Y. Yuan, S. H. Yang, and D. Xing, “Optical-resolution photoacoustic microscopy based on two-dimensional scanning galvanometer,” Appl. Phys. Lett.100(2), 023702 (2012).
[CrossRef]

J. Yao, K. I. Maslov, E. R. Puckett, K. J. Rowland, B. W. Warner, and L. V. Wang, “Double-illumination photoacoustic microscopy,” Opt. Lett.37(4), 659–661 (2012).
[CrossRef] [PubMed]

2011 (4)

S. Hu, K. Maslov, and L. V. Wang, “Second-generation optical-resolution photoacoustic microscopy with improved sensitivity and speed,” Opt. Lett.36(7), 1134–1136 (2011).
[CrossRef] [PubMed]

P. Hajireza, W. Shi, and R. J. Zemp, “Real-time handheld optical-resolution photoacoustic microscopy,” Opt. Express19(21), 20097–20102 (2011).
[CrossRef] [PubMed]

V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
[CrossRef] [PubMed]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
[CrossRef] [PubMed]

2010 (6)

2009 (3)

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics3(9), 503–509 (2009).
[CrossRef] [PubMed]

S. Hu, K. Maslov, V. Tsytsarev, and L. V. Wang, “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy,” J. Biomed. Opt.14(4), 040503 (2009).
[CrossRef] [PubMed]

Z. Xie, S. Jiao, H. F. Zhang, and C. A. Puliafito, “Laser-scanning optical-resolution photoacoustic microscopy,” Opt. Lett.34(12), 1771–1773 (2009).
[CrossRef] [PubMed]

2008 (2)

H. Wang, D. Xing, and L. Z. Xiang, “Photoacoustic imaging using an ultrasonic Fresnel zone plate transducer,” J. Phys. D Appl. Phys.41(9), 095111 (2008).
[CrossRef]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett.33(9), 929–931 (2008).
[CrossRef] [PubMed]

2006 (1)

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol.24(7), 848–851 (2006).
[CrossRef] [PubMed]

1994 (1)

J. M. Boone and J. A. Seibert, “An analytical edge spread function model for computer fitting and subsequent calculation of the LSF and MTF,” Med. Phys.21(10), 1541–1545 (1994).
[CrossRef] [PubMed]

Barbour, D. L.

V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
[CrossRef] [PubMed]

Boone, J. M.

J. M. Boone and J. A. Seibert, “An analytical edge spread function model for computer fitting and subsequent calculation of the LSF and MTF,” Med. Phys.21(10), 1541–1545 (1994).
[CrossRef] [PubMed]

Cai, X.

Chen, R.

C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
[CrossRef] [PubMed]

Deng, Y.

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

Deng, Z. L.

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
[CrossRef] [PubMed]

Gong, H.

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
[CrossRef] [PubMed]

Hajireza, P.

Hu, S.

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science335(6075), 1458–1462 (2012).
[CrossRef] [PubMed]

C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
[CrossRef] [PubMed]

V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
[CrossRef] [PubMed]

S. Hu, K. Maslov, and L. V. Wang, “Second-generation optical-resolution photoacoustic microscopy with improved sensitivity and speed,” Opt. Lett.36(7), 1134–1136 (2011).
[CrossRef] [PubMed]

S. Hu and L. V. Wang, “Photoacoustic imaging and characterization of the microvasculature,” J. Biomed. Opt.15(1), 011101 (2010).
[CrossRef] [PubMed]

S. Hu, K. Maslov, V. Tsytsarev, and L. V. Wang, “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy,” J. Biomed. Opt.14(4), 040503 (2009).
[CrossRef] [PubMed]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett.33(9), 929–931 (2008).
[CrossRef] [PubMed]

Jiang, B. W.

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

Jiao, S.

Krumholz, A.

A. Krumholz, L. Wang, J. Yao, and L. V. Wang, “Functional photoacoustic microscopy of diabetic vasculature,” J. Biomed. Opt.17(6), 060502 (2012).
[CrossRef] [PubMed]

Ku, G.

G. Ku, K. Maslov, L. Li, and L. V. Wang, “Photoacoustic microscopy with 2-microm transverse resolution,” J. Biomed. Opt.15(2), 021302 (2010).
[CrossRef] [PubMed]

Li, L.

G. Ku, K. Maslov, L. Li, and L. V. Wang, “Photoacoustic microscopy with 2-microm transverse resolution,” J. Biomed. Opt.15(2), 021302 (2010).
[CrossRef] [PubMed]

B. Rao, L. Li, K. Maslov, and L. Wang, “Hybrid-scanning optical-resolution photoacoustic microscopy for in vivo vasculature imaging,” Opt. Lett.35(10), 1521–1523 (2010).
[CrossRef] [PubMed]

Liu, Y.

Y. Liu, C. Zhang, and L. V. Wang, “Effects of light scattering on optical-resolution photoacoustic microscopy,” J. Biomed. Opt.17(12), 126014 (2012).
[CrossRef] [PubMed]

Liu, Y. Y.

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

Luo, Q. M.

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
[CrossRef] [PubMed]

X. Q. Yang, X. Cai, K. Maslov, L. V. Wang, and Q. M. Luo, “High-resolution photoacoustic microscope for rat brain imaging in vivo,” Chin. Opt. Lett.8(6), 609–611 (2010).
[CrossRef]

Maslov, K.

C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
[CrossRef] [PubMed]

V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
[CrossRef] [PubMed]

S. Hu, K. Maslov, and L. V. Wang, “Second-generation optical-resolution photoacoustic microscopy with improved sensitivity and speed,” Opt. Lett.36(7), 1134–1136 (2011).
[CrossRef] [PubMed]

D. K. Yao, K. Maslov, K. K. Shung, Q. Zhou, and L. V. Wang, “In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA,” Opt. Lett.35(24), 4139–4141 (2010).
[CrossRef] [PubMed]

B. Rao, L. Li, K. Maslov, and L. Wang, “Hybrid-scanning optical-resolution photoacoustic microscopy for in vivo vasculature imaging,” Opt. Lett.35(10), 1521–1523 (2010).
[CrossRef] [PubMed]

X. Q. Yang, X. Cai, K. Maslov, L. V. Wang, and Q. M. Luo, “High-resolution photoacoustic microscope for rat brain imaging in vivo,” Chin. Opt. Lett.8(6), 609–611 (2010).
[CrossRef]

G. Ku, K. Maslov, L. Li, and L. V. Wang, “Photoacoustic microscopy with 2-microm transverse resolution,” J. Biomed. Opt.15(2), 021302 (2010).
[CrossRef] [PubMed]

S. Hu, K. Maslov, V. Tsytsarev, and L. V. Wang, “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy,” J. Biomed. Opt.14(4), 040503 (2009).
[CrossRef] [PubMed]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett.33(9), 929–931 (2008).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol.24(7), 848–851 (2006).
[CrossRef] [PubMed]

Maslov, K. I.

J. Yao, K. I. Maslov, E. R. Puckett, K. J. Rowland, B. W. Warner, and L. V. Wang, “Double-illumination photoacoustic microscopy,” Opt. Lett.37(4), 659–661 (2012).
[CrossRef] [PubMed]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
[CrossRef] [PubMed]

Puckett, E. R.

Puliafito, C. A.

Rao, B.

Rowland, K. J.

Seibert, J. A.

J. M. Boone and J. A. Seibert, “An analytical edge spread function model for computer fitting and subsequent calculation of the LSF and MTF,” Med. Phys.21(10), 1541–1545 (1994).
[CrossRef] [PubMed]

Shi, W.

Shung, K. K.

C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
[CrossRef] [PubMed]

D. K. Yao, K. Maslov, K. K. Shung, Q. Zhou, and L. V. Wang, “In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA,” Opt. Lett.35(24), 4139–4141 (2010).
[CrossRef] [PubMed]

Stoica, G.

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol.24(7), 848–851 (2006).
[CrossRef] [PubMed]

Tsytsarev, V.

V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
[CrossRef] [PubMed]

S. Hu, K. Maslov, V. Tsytsarev, and L. V. Wang, “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy,” J. Biomed. Opt.14(4), 040503 (2009).
[CrossRef] [PubMed]

Wang, H.

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
[CrossRef] [PubMed]

H. Wang, D. Xing, and L. Z. Xiang, “Photoacoustic imaging using an ultrasonic Fresnel zone plate transducer,” J. Phys. D Appl. Phys.41(9), 095111 (2008).
[CrossRef]

Wang, L.

A. Krumholz, L. Wang, J. Yao, and L. V. Wang, “Functional photoacoustic microscopy of diabetic vasculature,” J. Biomed. Opt.17(6), 060502 (2012).
[CrossRef] [PubMed]

B. Rao, L. Li, K. Maslov, and L. Wang, “Hybrid-scanning optical-resolution photoacoustic microscopy for in vivo vasculature imaging,” Opt. Lett.35(10), 1521–1523 (2010).
[CrossRef] [PubMed]

Wang, L. V.

C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
[CrossRef] [PubMed]

A. Krumholz, L. Wang, J. Yao, and L. V. Wang, “Functional photoacoustic microscopy of diabetic vasculature,” J. Biomed. Opt.17(6), 060502 (2012).
[CrossRef] [PubMed]

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science335(6075), 1458–1462 (2012).
[CrossRef] [PubMed]

J. Yao, K. I. Maslov, E. R. Puckett, K. J. Rowland, B. W. Warner, and L. V. Wang, “Double-illumination photoacoustic microscopy,” Opt. Lett.37(4), 659–661 (2012).
[CrossRef] [PubMed]

Y. Liu, C. Zhang, and L. V. Wang, “Effects of light scattering on optical-resolution photoacoustic microscopy,” J. Biomed. Opt.17(12), 126014 (2012).
[CrossRef] [PubMed]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
[CrossRef] [PubMed]

S. Hu, K. Maslov, and L. V. Wang, “Second-generation optical-resolution photoacoustic microscopy with improved sensitivity and speed,” Opt. Lett.36(7), 1134–1136 (2011).
[CrossRef] [PubMed]

V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
[CrossRef] [PubMed]

X. Q. Yang, X. Cai, K. Maslov, L. V. Wang, and Q. M. Luo, “High-resolution photoacoustic microscope for rat brain imaging in vivo,” Chin. Opt. Lett.8(6), 609–611 (2010).
[CrossRef]

D. K. Yao, K. Maslov, K. K. Shung, Q. Zhou, and L. V. Wang, “In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA,” Opt. Lett.35(24), 4139–4141 (2010).
[CrossRef] [PubMed]

J. Yao and L. V. Wang, “Transverse flow imaging based on photoacoustic Doppler bandwidth broadening,” J. Biomed. Opt.15(2), 021304 (2010).
[CrossRef] [PubMed]

G. Ku, K. Maslov, L. Li, and L. V. Wang, “Photoacoustic microscopy with 2-microm transverse resolution,” J. Biomed. Opt.15(2), 021302 (2010).
[CrossRef] [PubMed]

S. Hu and L. V. Wang, “Photoacoustic imaging and characterization of the microvasculature,” J. Biomed. Opt.15(1), 011101 (2010).
[CrossRef] [PubMed]

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics3(9), 503–509 (2009).
[CrossRef] [PubMed]

S. Hu, K. Maslov, V. Tsytsarev, and L. V. Wang, “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy,” J. Biomed. Opt.14(4), 040503 (2009).
[CrossRef] [PubMed]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett.33(9), 929–931 (2008).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol.24(7), 848–851 (2006).
[CrossRef] [PubMed]

Wang, Z.

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
[CrossRef] [PubMed]

Warner, B. W.

Xia, Y.

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
[CrossRef] [PubMed]

Xiang, L. Z.

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Xie, Z.

Xing, D.

Y. Yuan, S. H. Yang, and D. Xing, “Optical-resolution photoacoustic microscopy based on two-dimensional scanning galvanometer,” Appl. Phys. Lett.100(2), 023702 (2012).
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H. Wang, D. Xing, and L. Z. Xiang, “Photoacoustic imaging using an ultrasonic Fresnel zone plate transducer,” J. Phys. D Appl. Phys.41(9), 095111 (2008).
[CrossRef]

Xu, G. Q.

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
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Yang, S. H.

Y. Yuan, S. H. Yang, and D. Xing, “Optical-resolution photoacoustic microscopy based on two-dimensional scanning galvanometer,” Appl. Phys. Lett.100(2), 023702 (2012).
[CrossRef]

Yang, X. Q.

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
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X. Q. Yang, X. Cai, K. Maslov, L. V. Wang, and Q. M. Luo, “High-resolution photoacoustic microscope for rat brain imaging in vivo,” Chin. Opt. Lett.8(6), 609–611 (2010).
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Yao, D. K.

Yao, J.

A. Krumholz, L. Wang, J. Yao, and L. V. Wang, “Functional photoacoustic microscopy of diabetic vasculature,” J. Biomed. Opt.17(6), 060502 (2012).
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J. Yao, K. I. Maslov, E. R. Puckett, K. J. Rowland, B. W. Warner, and L. V. Wang, “Double-illumination photoacoustic microscopy,” Opt. Lett.37(4), 659–661 (2012).
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J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
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V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
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J. Yao and L. V. Wang, “Transverse flow imaging based on photoacoustic Doppler bandwidth broadening,” J. Biomed. Opt.15(2), 021304 (2010).
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Yuan, Y.

Y. Yuan, S. H. Yang, and D. Xing, “Optical-resolution photoacoustic microscopy based on two-dimensional scanning galvanometer,” Appl. Phys. Lett.100(2), 023702 (2012).
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Zemp, R. J.

Zhang, C.

Y. Liu, C. Zhang, and L. V. Wang, “Effects of light scattering on optical-resolution photoacoustic microscopy,” J. Biomed. Opt.17(12), 126014 (2012).
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C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
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Zhang, H. F.

Zhang, Y.

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
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Zhou, Q.

C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
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D. K. Yao, K. Maslov, K. K. Shung, Q. Zhou, and L. V. Wang, “In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA,” Opt. Lett.35(24), 4139–4141 (2010).
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Appl. Phys. Lett. (1)

Y. Yuan, S. H. Yang, and D. Xing, “Optical-resolution photoacoustic microscopy based on two-dimensional scanning galvanometer,” Appl. Phys. Lett.100(2), 023702 (2012).
[CrossRef]

Chin. Opt. Lett. (1)

J. Biomed. Opt. (11)

S. Hu, K. Maslov, V. Tsytsarev, and L. V. Wang, “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy,” J. Biomed. Opt.14(4), 040503 (2009).
[CrossRef] [PubMed]

J. Yao, K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, “Label-free oxygen-metabolic photoacoustic microscopy in vivo,” J. Biomed. Opt.16(7), 076003 (2011).
[CrossRef] [PubMed]

Y. Y. Liu, X. Q. Yang, H. Gong, B. W. Jiang, H. Wang, G. Q. Xu, and Y. Deng, “Assessing the effects of norepinephrine on single cerebral microvessels using optical-resolution photoacoustic microscope,” J. Biomed. Opt.18(7), 076007 (2013).
[CrossRef] [PubMed]

V. Tsytsarev, S. Hu, J. Yao, K. Maslov, D. L. Barbour, and L. V. Wang, “Photoacoustic microscopy of microvascular responses to cortical electrical stimulation,” J. Biomed. Opt.16(7), 076002 (2011).
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S. Hu and L. V. Wang, “Photoacoustic imaging and characterization of the microvasculature,” J. Biomed. Opt.15(1), 011101 (2010).
[CrossRef] [PubMed]

H. Wang, X. Q. Yang, Z. Wang, Z. L. Deng, H. Gong, and Q. M. Luo, “Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy,” J. Biomed. Opt.17(6), 061207 (2012).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

G. Ku, K. Maslov, L. Li, and L. V. Wang, “Photoacoustic microscopy with 2-microm transverse resolution,” J. Biomed. Opt.15(2), 021302 (2010).
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C. Zhang, K. Maslov, S. Hu, R. Chen, Q. Zhou, K. K. Shung, and L. V. Wang, “Reflection-mode submicron-resolution in vivo photoacoustic microscopy,” J. Biomed. Opt.17(2), 020501 (2012).
[CrossRef] [PubMed]

J. Phys. D Appl. Phys. (1)

H. Wang, D. Xing, and L. Z. Xiang, “Photoacoustic imaging using an ultrasonic Fresnel zone plate transducer,” J. Phys. D Appl. Phys.41(9), 095111 (2008).
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H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol.24(7), 848–851 (2006).
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Opt. Lett. (6)

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Figures (6)

Fig. 1
Fig. 1

Schematic of the OR-PAM system based on a reflective objective. (AspL, aspheric lens; ND, neutral density; FC, fiber coupler; SMF, single-mode fiber; PD, photodiode; US, ultrasonic transducer; BS, beam sampler; CorL, correction lens.)

Fig. 2
Fig. 2

Spatial resolution of the OR-PAM system. (a) Lateral resolution measurement on a sharp edge in an Air Force resolution test target. ESF, edge spread function. Blue circle: experimental measurement. Red solid line: theoretical fit. (b) LSF derived from the fitted ESF. LSF, line spread function. (c) Axial profile of a typical 0.5 μm carbon nanoparticle. Blue line with circle: experimental signal. Red solid line: envelope of the experimental signal.

Fig. 3
Fig. 3

Measurement of the penetration depth of the OR-PAM system. (a) A black tape, inserted obliquely into chicken’s breast, is imaged clearly down to 0.9 mm below the referenced surface. (b) Several human hairs are imaged at different depths in chicken’s breast. The hair down to 0.92 mm below the surface is still clearly visible in the image.

Fig. 4
Fig. 4

Microvasculature in a mouse ear imaged in vivo using our OR-PAM system. (a) Photograph of the mouse ear. The imaging area is indicated with a box. (b) Volumetric rendering of the PA imaging of microvasculature in the imaging area. (c) MAP image of (b) along z-axis. (d) A close-up MAP image in the area indicated by a box in (c) with a projection depth of 50 μm under the surface of the ear. The image shows the detailed micro blood vessels, including a capillary bed indicated by a circle.

Fig. 5
Fig. 5

In vivo imaging of microvasculature in mouse ear. (a) MAP image of a 0.5 mm × 1.2 mm area of a mouse ear. (b) MAP image of micro blood vessels in superficial layer of the ear where the capillary network can be shown. (c) 3-D view of three MAP images from three parallel layers beneath the skin surface, the layer spacing is 60 μm. (d) Close-up of the capillaries enclosed by the box in (b), where these discrete points may be the RBCs.

Fig. 6
Fig. 6

In vitro images of mouse RBCs. (a) MAP PA image. (b) Image from optical microscope (0.3 NA). The images are shown with the same scale bar.

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