Abstract

The range of imaging depth in optical resolution photoacoustic microscopy (PAM) is limited by the short depth of focus of high-numerical aperture objective lenses. In this paper, focus tunable lens modulation has been employed at the resonant frequency of focus tunable lenses in order to enhance both the range of imaging depth and the scanning speed. By electrically controlling the focal length in the axial direction of the sample, the range of imaging depth was extended approximately 1.22 times and the scanning speed was enhanced by approximately 7.40 times, in comparison to corresponding values of conventional PAM systems.

© 2017 Optical Society of America

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References

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2015 (1)

J. Y. Kim, C. Lee, K. Park, G. Lim, and C. Kim, “Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner,” Sci. Rep. 5, 7932 (2015).
[PubMed]

2014 (2)

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

B. Li, H. Qin, S. Yang, and D. Xing, “In vivo fast variable focus photoacoustic microscopy using an electrically tunable lens,” Opt. Express 22(17), 20130–20137 (2014).
[PubMed]

2013 (1)

2012 (6)

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).
[PubMed]

Z. Chen, S. Yang, and D. Xing, “In vivo detection of hemoglobin oxygen saturation and carboxyhemoglobin saturation with multiwavelength photoacoustic microscopy,” Opt. Lett. 37(16), 3414–3416 (2012).
[PubMed]

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335(6075), 1458–1462 (2012).
[PubMed]

C. Zhang, K. Maslov, J. Yao, and L. V. Wang, “In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer,” J. Biomed. Opt. 17(11), 116016 (2012).
[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).

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

2011 (5)

2010 (2)

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

C. Zhang, K. Maslov, and L. V. Wang, “Subwavelength-resolution label-free photoacoustic microscopy of optical absorption in vivo,” Opt. Lett. 35(19), 3195–3197 (2010).
[PubMed]

2008 (1)

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).
[PubMed]

1984 (1)

Aschwanden, M.

M. Blum, M. Büeler, C. Grätzel, and M. Aschwanden, “Compact optical design solutions using focus tunable lenses,” in SPIE Proc. 8167, (2011).

Bauer, A. Q.

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

Beard, P.

Blum, M.

M. Blum, M. Büeler, C. Grätzel, and M. Aschwanden, “Compact optical design solutions using focus tunable lenses,” in SPIE Proc. 8167, (2011).

Büeler, M.

M. Blum, M. Büeler, C. Grätzel, and M. Aschwanden, “Compact optical design solutions using focus tunable lenses,” in SPIE Proc. 8167, (2011).

Chen, M. S.

H. C. Lin, M. S. Chen, and Y. H. Lin, “A review of electrically tunable focusing liquid crystal lenses,” Trans. Electric. Electron. Mater. 12(6), 234–240 (2011).

Chen, R.

Chen, Z.

Cohen, D. K.

Culver, J. P.

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

Danielli, A.

Fahrbach, F. O.

Gao, L.

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

Gee, W. H.

Grätzel, C.

M. Blum, M. Büeler, C. Grätzel, and M. Aschwanden, “Compact optical design solutions using focus tunable lenses,” in SPIE Proc. 8167, (2011).

Grewe, B. F.

Helmchen, F.

Hu, S.

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335(6075), 1458–1462 (2012).
[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).
[PubMed]

Huang, C. H.

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

Huisken, J.

Kim, C.

J. Y. Kim, C. Lee, K. Park, G. Lim, and C. Kim, “Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner,” Sci. Rep. 5, 7932 (2015).
[PubMed]

Kim, J. Y.

J. Y. Kim, C. Lee, K. Park, G. Lim, and C. Kim, “Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner,” Sci. Rep. 5, 7932 (2015).
[PubMed]

Ku, G.

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

Laufer, J.

Lee, C.

J. Y. Kim, C. Lee, K. Park, G. Lim, and C. Kim, “Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner,” Sci. Rep. 5, 7932 (2015).
[PubMed]

Lewkowicz, J.

Li, B.

Li, L.

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

Lim, G.

J. Y. Kim, C. Lee, K. Park, G. Lim, and C. Kim, “Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner,” Sci. Rep. 5, 7932 (2015).
[PubMed]

Lin, H. C.

H. C. Lin, M. S. Chen, and Y. H. Lin, “A review of electrically tunable focusing liquid crystal lenses,” Trans. Electric. Electron. Mater. 12(6), 234–240 (2011).

Lin, Y. H.

H. C. Lin, M. S. Chen, and Y. H. Lin, “A review of electrically tunable focusing liquid crystal lenses,” Trans. Electric. Electron. Mater. 12(6), 234–240 (2011).

Ludeke, M.

Maslov, K.

Maslov, K. I.

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[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).
[PubMed]

Nasiriavanaki, M.

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

Park, K.

J. Y. Kim, C. Lee, K. Park, G. Lim, and C. Kim, “Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner,” Sci. Rep. 5, 7932 (2015).
[PubMed]

Puckett, E. R.

Qin, H.

Rao, B.

Rowland, K. J.

Schmid, B.

Shung, K. K.

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).
[PubMed]

van ’t Hoff, M.

Voigt, F. F.

Wan, H.

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

Wang, L.

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, “Fast voice-coil scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 36(2), 139–141 (2011).
[PubMed]

Wang, L. V.

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335(6075), 1458–1462 (2012).
[PubMed]

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

C. Zhang, K. Maslov, J. Yao, and L. V. Wang, “In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer,” J. Biomed. Opt. 17(11), 116016 (2012).
[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).
[PubMed]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, “Fast voice-coil scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 36(2), 139–141 (2011).
[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).
[PubMed]

B. Rao, K. Maslov, A. Danielli, R. Chen, K. K. Shung, Q. Zhou, and L. V. Wang, “Real-time four-dimensional optical-resolution photoacoustic microscopy with Au nanoparticle-assisted subdiffraction-limit resolution,” Opt. Lett. 36(7), 1137–1139 (2011).
[PubMed]

C. Zhang, K. Maslov, and L. V. Wang, “Subwavelength-resolution label-free photoacoustic microscopy of optical absorption in vivo,” Opt. Lett. 35(19), 3195–3197 (2010).
[PubMed]

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

Warner, B. W.

Xia, J.

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

Xing, D.

Yang, J. M.

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

Yang, S.

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).

Yao, J.

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

C. Zhang, K. Maslov, J. Yao, and L. V. Wang, “In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer,” J. Biomed. Opt. 17(11), 116016 (2012).
[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).
[PubMed]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, “Fast voice-coil scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 36(2), 139–141 (2011).
[PubMed]

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).

Zhang, C.

C. Zhang, K. Maslov, J. Yao, and L. V. Wang, “In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer,” J. Biomed. Opt. 17(11), 116016 (2012).
[PubMed]

C. Zhang, K. Maslov, and L. V. Wang, “Subwavelength-resolution label-free photoacoustic microscopy of optical absorption in vivo,” Opt. Lett. 35(19), 3195–3197 (2010).
[PubMed]

Zhang, E.

Zhang, H. F.

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).
[PubMed]

Zhou, Q.

Zou, J.

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

Appl. Opt. (2)

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).

Biomed. Opt. Express (1)

J. Biomed. Opt. (3)

J. Yao, C. H. Huang, L. Wang, J. M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, “Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror,” J. Biomed. Opt. 17(8), 080505 (2012).
[PubMed]

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

C. Zhang, K. Maslov, J. Yao, and L. V. Wang, “In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer,” J. Biomed. Opt. 17(11), 116016 (2012).
[PubMed]

Nat. Biotechnol. (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).
[PubMed]

Opt. Express (2)

Opt. Lett. (6)

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

M. Nasiriavanaki, J. Xia, H. Wan, A. Q. Bauer, J. P. Culver, and L. V. Wang, “High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain,” Proc. Natl. Acad. Sci. U.S.A. 111(1), 21–26 (2014).
[PubMed]

Sci. Rep. (1)

J. Y. Kim, C. Lee, K. Park, G. Lim, and C. Kim, “Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner,” Sci. Rep. 5, 7932 (2015).
[PubMed]

Science (1)

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335(6075), 1458–1462 (2012).
[PubMed]

Trans. Electric. Electron. Mater. (1)

H. C. Lin, M. S. Chen, and Y. H. Lin, “A review of electrically tunable focusing liquid crystal lenses,” Trans. Electric. Electron. Mater. 12(6), 234–240 (2011).

Other (3)

M. Blum, M. Büeler, C. Grätzel, and M. Aschwanden, “Compact optical design solutions using focus tunable lenses,” in SPIE Proc. 8167, (2011).

Optotune Datasheet, “Fast electrically tunable lens EL-10-30 series ”, Optotune, (2013)

K. Ogata, “System Dynamics,” 4th Ed, Prentice Hall, (2004)

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Figures (8)

Fig. 1
Fig. 1

Schematic of the proposed PAM, where FG is the function generator; CL is a convex lens; ND is the neutral density filter; PH is the pin hole; FTL is the focus tunable lens; TL is the tube lens; OL is the objective lens; WT is the water tank; UT is the ultrasonic transducer; LPF is the low pass filter; and LNA is the low noise amplifier.

Fig. 2
Fig. 2

Relationship between the scanning range and modulation frequency. (a) The modulation frequency of the FTL is lower than the settling frequency. (b) The modulation frequency of the FTL is higher than the settling frequency and lower than the resonant frequency. (c) The resonant frequency is used as the modulation frequency. (d) The modulation frequency of the FTL is higher than the resonant frequency.

Fig. 3
Fig. 3

Measurement method used to determine the PA range of imaging depth as the modulation frequency changes. (a) PA signals are measured at each focal position by moving the sample along the x-axis. Laser beams are in focus and the PA signals are strong at positions X2, X3, and X4. Sample positions X1 and X5 are out of focus and weakly illuminated. (b) Envelope of the PA signals is generated by interlinking the values at each sample position. The range of imaging depth is defined as the FWHM of the envelope.

Fig. 4
Fig. 4

(a) Envelopes of the collected maximum PA signals at modulation frequencies of 50, 200, and 370 Hz, respectively. (b) Range of imaging depth at modulation frequencies ranging from 50 to 800 Hz.

Fig. 5
Fig. 5

Lateral and axial resolutions of the proposed PAM system. (a) ESF fitted to experimental data, and the corresponding LSF based on the first derivative of the ESF. (b) LSF fitted from experimental data.

Fig. 6
Fig. 6

B-scan PA image of a human hair with top (green) and bottom (orange) illumination at 50 Hz (a), 200 Hz (b), and 370 Hz (c).

Fig. 7
Fig. 7

Maximum PA amplitude for top and bottom illumination in the axial position. (a) Normalized PA amplitudes for the top illumination (green dots) and bottom illumination (orange dots) at the resonant frequency. Each dot indicates the maximum value of the acquired PA signals. (b) Normalized PA amplitudes at each modulation frequency. The extended imaging depth was about 0.77 mm beyond merging point of the top and bottom PA signals at the resonant frequency.

Fig. 8
Fig. 8

In vivo PA images of the ear of a mouse. (a) photograph of the ear, (b) PA image with top illumination, (c) side-view image indicated by the dashed line box in (b), (d) PA image with bottom illumination, (e) side-view image indicated by the dashed line box in (d), (f) merged PA image of the top (a) and bottom (b) illuminations, and (g) side-view image indicated by the dashed line box in (f).

Equations (1)

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f s t = 1 s e t t l i n g t i m e

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