Abstract

We developed random-access optical-resolution photoacoustic microscopy using a digital micromirror device. This system can rapidly scan arbitrarily shaped regions of interest within a 40μm×40μm imaging area with a lateral resolution of 3.6 μm. To identify a region of interest, a global structural image is first acquired, then the selected region is scanned. The random-access ability was demonstrated by imaging two static samples, a carbon fiber cross and a monolayer of red blood cells, with an acquisition rate up to 4 kHz. The system was then used to monitor blood flow in vivo in real time within user-selected capillaries in a mouse ear. By imaging only the capillary of interest, the frame rate was increased by up to 9.2 times.

© 2013 Optical Society of America

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L. Wang, K. Maslov, and L. V. Wang, Proc. Natl. Acad. Sci. USA 110, 5759 doi: 10.1073/pnas.1215578110 (2013).
[CrossRef]

R. Li, M. N. Slipchenko, P. Wang, and J.-X. Cheng, J. Biomed. Opt. 18, 040502 (2013).
[CrossRef]

G. Li, K. I. Maslov, and L. V. Wang, J. Biomed. Opt. 18, 030501 (2013).
[CrossRef]

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

2012

V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

A. Kocabas, C.-H. Shen, Z. V. Guo, and S. Ramanathan, Nature 490, 273 (2012).
[CrossRef]

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

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

2011

2010

2008

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
[CrossRef]

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, Nat. Neurosci. 11, 713 (2008).
[CrossRef]

2006

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

2003

D. Dudley, W. M. Duncan, and J. Slaughter, Proc. SPIE 4985, 14 (2003).
[CrossRef]

2000

1999

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Hanley, Verveer, Gemkow, J. Arndt, and Jovin, J. Microsc. 196, 317 (1999).
[CrossRef]

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V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

Bourdieu, L.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Candes, E.

V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

Chahid, M.

V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

Chatenay, D.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Cheng, A.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

Cheng, J.-X.

R. Li, M. N. Slipchenko, P. Wang, and J.-X. Cheng, J. Biomed. Opt. 18, 040502 (2013).
[CrossRef]

Dahan, M.

V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

Dieudonné, S.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Dlugan, A. L. P.

Dudley, D.

D. Dudley, W. M. Duncan, and J. Slaughter, Proc. SPIE 4985, 14 (2003).
[CrossRef]

Duemani Reddy, G.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, Nat. Neurosci. 11, 713 (2008).
[CrossRef]

Duncan, W. M.

D. Dudley, W. M. Duncan, and J. Slaughter, Proc. SPIE 4985, 14 (2003).
[CrossRef]

Fawzi, A.

Fink, R.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, Nat. Neurosci. 11, 713 (2008).
[CrossRef]

Forbrich, A. E.

Gao, L.

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

Gemkow,

Hanley, Verveer, Gemkow, J. Arndt, and Jovin, J. Microsc. 196, 317 (1999).
[CrossRef]

Guo, Z. V.

A. Kocabas, C.-H. Shen, Z. V. Guo, and S. Ramanathan, Nature 490, 273 (2012).
[CrossRef]

Hanley,

Hanley, Verveer, Gemkow, J. Arndt, and Jovin, J. Microsc. 196, 317 (1999).
[CrossRef]

Hitt, M. M.

Hu, J.

Hu, S.

Huang, C.-H.

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

Jiang, M.

Jiao, S.

Jovin,

Hanley, Verveer, Gemkow, J. Arndt, and Jovin, J. Microsc. 196, 317 (1999).
[CrossRef]

Kelleher, K.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, Nat. Neurosci. 11, 713 (2008).
[CrossRef]

Kocabas, A.

A. Kocabas, C.-H. Shen, Z. V. Guo, and S. Ramanathan, Nature 490, 273 (2012).
[CrossRef]

Kremer, Y.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Krichevsky, O.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Lakhiani, C.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

Lane, P. M.

Léger, J. F.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Li, G.

G. Li, K. I. Maslov, and L. V. Wang, J. Biomed. Opt. 18, 030501 (2013).
[CrossRef]

Li, R.

R. Li, M. N. Slipchenko, P. Wang, and J.-X. Cheng, J. Biomed. Opt. 18, 040502 (2013).
[CrossRef]

Liang, J.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

Livingston, E. H.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

MacAulay, C. E.

Mangum, M.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

Maslov, K.

Maslov, K. I.

G. Li, K. I. Maslov, and L. V. Wang, J. Biomed. Opt. 18, 030501 (2013).
[CrossRef]

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

Mousavi, H. S.

V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

Paproski, R. J.

Puliafito, C. A.

Ramanathan, S.

A. Kocabas, C.-H. Shen, Z. V. Guo, and S. Ramanathan, Nature 490, 273 (2012).
[CrossRef]

Rao, B.

Richards-Kortum, R.

Saggau, P.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, Nat. Neurosci. 11, 713 (2008).
[CrossRef]

Saint-Cyr, M.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

Salomé, R.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Shen, C.-H.

A. Kocabas, C.-H. Shen, Z. V. Guo, and S. Ramanathan, Nature 490, 273 (2012).
[CrossRef]

Shung, K. K.

Slaughter, J.

D. Dudley, W. M. Duncan, and J. Slaughter, Proc. SPIE 4985, 14 (2003).
[CrossRef]

Slipchenko, M. N.

R. Li, M. N. Slipchenko, P. Wang, and J.-X. Cheng, J. Biomed. Opt. 18, 040502 (2013).
[CrossRef]

Studer, V.

V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

Teotia, S.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

Verveer,

Hanley, Verveer, Gemkow, J. Arndt, and Jovin, J. Microsc. 196, 317 (1999).
[CrossRef]

Wachowicz, K.

Wang, L.

L. Wang, K. Maslov, and L. V. Wang, Proc. Natl. Acad. Sci. USA 110, 5759 doi: 10.1073/pnas.1215578110 (2013).
[CrossRef]

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, Opt. Lett. 36, 139 (2011).
[CrossRef]

Wang, L. V.

L. Wang, K. Maslov, and L. V. Wang, Proc. Natl. Acad. Sci. USA 110, 5759 doi: 10.1073/pnas.1215578110 (2013).
[CrossRef]

G. Li, K. I. Maslov, and L. V. Wang, J. Biomed. Opt. 18, 030501 (2013).
[CrossRef]

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

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

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, Opt. Lett. 36, 139 (2011).
[CrossRef]

S. Hu, K. Maslov, and L. V. Wang, Opt. Lett. 36, 1134 (2011).
[CrossRef]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
[CrossRef]

Wang, P.

R. Li, M. N. Slipchenko, P. Wang, and J.-X. Cheng, J. Biomed. Opt. 18, 040502 (2013).
[CrossRef]

Wyart, C.

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Yang, J.-M.

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

Yao, J.

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

L. Wang, K. Maslov, J. Yao, B. Rao, and L. V. Wang, Opt. Lett. 36, 139 (2011).
[CrossRef]

Zemp, R. J.

Zhang, H. F.

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, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

Zuzak, K. J.

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

Biomed. Opt. Express

J. Biomed. Opt.

R. Li, M. N. Slipchenko, P. Wang, and J.-X. Cheng, J. Biomed. Opt. 18, 040502 (2013).
[CrossRef]

J. Yao, C.-H. Huang, L. Wang, J.-M. Yang, L. Gao, K. I. Maslov, J. Zou, and L. V. Wang, J. Biomed. Opt. 17, 080505 (2012).
[CrossRef]

G. Li, K. I. Maslov, and L. V. Wang, J. Biomed. Opt. 18, 030501 (2013).
[CrossRef]

J. Microsc.

Hanley, Verveer, Gemkow, J. Arndt, and Jovin, J. Microsc. 196, 317 (1999).
[CrossRef]

J. Neurosci. Methods

R. Salomé, Y. Kremer, S. Dieudonné, J. F. Léger, O. Krichevsky, C. Wyart, D. Chatenay, and L. Bourdieu, J. Neurosci. Methods 154, 161 (2006).
[CrossRef]

Nat. Neurosci.

G. Duemani Reddy, K. Kelleher, R. Fink, and P. Saggau, Nat. Neurosci. 11, 713 (2008).
[CrossRef]

Nature

A. Kocabas, C.-H. Shen, Z. V. Guo, and S. Ramanathan, Nature 490, 273 (2012).
[CrossRef]

Opt. Express

Opt. Lett.

Proc. Natl. Acad. Sci. USA

V. Studer, J. Bobin, M. Chahid, H. S. Mousavi, E. Candes, and M. Dahan, Proc. Natl. Acad. Sci. USA 109, E1679 (2012).
[CrossRef]

L. Wang, K. Maslov, and L. V. Wang, Proc. Natl. Acad. Sci. USA 110, 5759 doi: 10.1073/pnas.1215578110 (2013).
[CrossRef]

Proc. SPIE

M. Saint-Cyr, C. Lakhiani, A. Cheng, M. Mangum, J. Liang, S. Teotia, E. H. Livingston, and K. J. Zuzak, Proc. SPIE 8618, 861806 (2013).
[CrossRef]

D. Dudley, W. M. Duncan, and J. Slaughter, Proc. SPIE 4985, 14 (2003).
[CrossRef]

Science

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

Supplementary Material (8)

» Media 1: AVI (3131 KB)     
» Media 2: AVI (14973 KB)     
» Media 3: AVI (14745 KB)     
» Media 4: AVI (13041 KB)     
» Media 5: AVI (3926 KB)     
» Media 6: AVI (4095 KB)     
» Media 7: AVI (3297 KB)     
» Media 8: AVI (3822 KB)     

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Figures (6)

Fig. 1.
Fig. 1.

Schematic overview of the RA-OR-PAM system, not to scale. AMP, signal amplifiers and filters; DAQ, data acquisition; DMD, digital micromirror device; L1–L3, lenses (focal lengths: f1=100mm, f2=30mm, and f3=160mm); M, mirror; OL, objective lens (Olympus, 100×, NA 1.4 oil-immersion); UT, ultrasound transducer; and W, water.

Fig. 2.
Fig. 2.

Quantification of the lateral resolution of the RA-OR-PAM system. (a) PA image of an edge made of deposited chromium. (b) ESF extracted from (a). (c) LSF extracted from (b) and interpolated with cubic spline.

Fig. 3.
Fig. 3.

PA images of a carbon-fiber cross acquired using four scanning methods: (a) global raster scanning, (b) 5-point cross pattern, (c) central row of the horizontal fiber, and (d) cross sections on the two fibers on both ends. The entire scanning area is 40μm×40μm.

Fig. 4.
Fig. 4.

PA imaging of a monolayer of RBC using (a) global raster scanning and (b) random-access scanning. The entire scanning area is 40μm×40μm.

Fig. 5.
Fig. 5.

Real-time imaging of capillary features and blood flow dynamics in a mouse ear in vivo. (a) 3D view of two crossed capillaries at different depths (Media 1), (b) flow dynamics of the structure in (a) (Media 2), (c) RBC clusters flowing through a loop capillary with a bifurcation (Media 3), and (d) capillary clogging and reperfusion (Media 4).

Fig. 6.
Fig. 6.

Real-time imaging of blood flow in a mouse ear in a loop capillary in vivo using (a) global raster scanning (Media 5) and (b) random-access scanning (Media 6). A capillary bifurcation was also imaged using (c) global raster scanning (Media 7) and (d) random-access scanning (Media 8).

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