Abstract

In deep-tissue photoacoustic imaging, optical-contrast images of deep-lying structures are formed by recording acoustic waves that are generated by optical absorption. Although photoacoustics is perhaps the leading technique for high-resolution deep-tissue optical imaging, its spatial resolution is fundamentally limited by the acoustic wavelength, which is orders of magnitude longer than the optical diffraction limit. Here, we present an approach for surpassing the acoustic diffraction limit in photoacoustics by exploiting inherent temporal fluctuations in the photoacoustic signals due to sample dynamics, such as those induced by the flow of absorbing red blood cells. This was achieved using a conventional photoacoustic imaging system by adapting concepts from super-resolution fluorescence fluctuation microscopy to the statistical analysis of acoustic signals from flowing acoustic emitters. Specifically, we experimentally demonstrate that flow of absorbing particles and whole human blood yields super-resolved photoacoustic images, and provides static background reduction. By generalizing the statistical analysis to complex-valued signals, we demonstrate super-resolved photoacoustic images that are free from common photoacoustic imaging artifacts caused by band-limited acoustic detection. The presented technique holds potential for contrast-agent-free microvessel imaging, as red blood cells provide a strong endogenous source of naturally fluctuating absorption.

© 2017 Optical Society of America

Full Article  |  PDF Article
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References

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  1. V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7, 603–614 (2010).
    [Crossref]
  2. L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335, 1458–1462 (2012).
    [Crossref]
  3. P. Beard, “Biomedical photoacoustic imaging,” Interface Focus 1, 602–631 (2011).
    [Crossref]
  4. M. Omar, D. Soliman, J. Gateau, and V. Ntziachristos, “Ultrawideband reflection-mode optoacoustic mesoscopy,” Opt. Lett. 39, 3911–3914 (2014).
    [Crossref]
  5. D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9, 713–725 (2003).
    [Crossref]
  6. T. Chaigne, J. Gateau, M. Allain, O. Katz, S. Gigan, A. Sentenac, and E. Bossy, “Super-resolution photoacoustic fluctuation imaging with multiple speckle illumination,” Optica 3, 54–57 (2016).
    [Crossref]
  7. T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
    [Crossref]
  8. E. Hojman, T. Chaigne, O. Solomon, S. Gigan, E. Bossy, Y. C. Eldar, and O. Katz, “Photoacoustic imaging beyond the acoustic diffraction-limit with dynamic speckle illumination and sparse joint support recovery,” Opt. Express 25, 4875–4886 (2017).
    [Crossref]
  9. T. W. Murray, M. Haltmeier, T. Berer, E. Leiss-Holzinger, and P. Burgholzer, “Super-resolution photoacoustic microscopy using blind structured illumination,” Optica 4, 17–22 (2017).
    [Crossref]
  10. J. W. Goodman, Speckle Phenomena in Optics: Theory and Applications (Roberts, 2007).
  11. J. Gateau, T. Chaigne, O. Katz, S. Gigan, and E. Bossy, “Improving visibility in photoacoustic imaging using dynamic speckle illumination,” Opt. Lett. 38, 5188–5191 (2013).
    [Crossref]
  12. C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
    [Crossref]
  13. A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
    [Crossref]
  14. X. L. Deán-Ben, L. Ding, and D. Razansky, “Dynamic particle enhancement in limited-view optoacoustic tomography,” Opt. Lett. 42, 827–830 (2017).
    [Crossref]
  15. S. Vilov, B. Arnal, and E. Bossy, “Overcoming the acoustic diffraction limit in photoacoustic imaging by localization of flowing absorbers,” Opt. Lett. 42, 4379–4382 (2017).
  16. X. L. Dean-Ben and D. Razansky, “Localization optoacoustic tomography,” arXiv:1707.02145 (2017).
  17. S. Tang and G. Whitesides, “Basic microfluidic and soft lithographic techniques,” in Optofluidics: Fundamentals, Devices and Applications (McGraw-Hill, 2010).
  18. C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
    [Crossref]
  19. T. W. Secomb, “Blood flow in the microcirculation,” Annu. Rev. Fluid Mech. 49, 443–461 (2017).
    [Crossref]
  20. J. Eriksson, E. Ollila, and V. Koivunen, “Essential statistics and tools for complex random variables,” IEEE Trans. Signal Process. 58, 5400–5408 (2010).
    [Crossref]
  21. X. Wang, D. Chen, B. Yu, and H. Niu, “Statistical precision in super-resolution optical fluctuation imaging,” Appl. Opt. 55, 7911–7916 (2016).
    [Crossref]
  22. S. Geissbuehler, C. Dellagiacoma, and T. Lasser, “Comparison between sofi and storm,” Biomed. Opt. Express 2, 408–420 (2011).
    [Crossref]
  23. J. D. Müller, “Cumulant analysis in fluorescence fluctuation spectroscopy,” Biophys. J. 86, 3981–3992 (2004).
    [Crossref]
  24. H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99, 184501 (2007).
    [Crossref]
  25. J. Brunker and P. Beard, “Acoustic resolution photoacoustic Doppler velocimetry in blood-mimicking fluids,” Sci. Rep. 6, 20902 (2016).
    [Crossref]
  26. J. Brunker and P. Beard, “Velocity measurements in whole blood using acoustic resolution photoacoustic Doppler,” Biomed. Opt. Express 7, 2789–2806 (2016).
    [Crossref]
  27. T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
    [Crossref]
  28. Y. Zhou, J. Yao, K. I. Maslov, and L. V. Wang, “Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo,” J. Biomed. Opt. 19, 037001 (2014).
    [Crossref]
  29. B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
    [Crossref]

2017 (8)

A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
[Crossref]

T. W. Secomb, “Blood flow in the microcirculation,” Annu. Rev. Fluid Mech. 49, 443–461 (2017).
[Crossref]

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
[Crossref]

T. W. Murray, M. Haltmeier, T. Berer, E. Leiss-Holzinger, and P. Burgholzer, “Super-resolution photoacoustic microscopy using blind structured illumination,” Optica 4, 17–22 (2017).
[Crossref]

X. L. Deán-Ben, L. Ding, and D. Razansky, “Dynamic particle enhancement in limited-view optoacoustic tomography,” Opt. Lett. 42, 827–830 (2017).
[Crossref]

E. Hojman, T. Chaigne, O. Solomon, S. Gigan, E. Bossy, Y. C. Eldar, and O. Katz, “Photoacoustic imaging beyond the acoustic diffraction-limit with dynamic speckle illumination and sparse joint support recovery,” Opt. Express 25, 4875–4886 (2017).
[Crossref]

S. Vilov, B. Arnal, and E. Bossy, “Overcoming the acoustic diffraction limit in photoacoustic imaging by localization of flowing absorbers,” Opt. Lett. 42, 4379–4382 (2017).

2016 (4)

2015 (2)

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

2014 (2)

Y. Zhou, J. Yao, K. I. Maslov, and L. V. Wang, “Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo,” J. Biomed. Opt. 19, 037001 (2014).
[Crossref]

M. Omar, D. Soliman, J. Gateau, and V. Ntziachristos, “Ultrawideband reflection-mode optoacoustic mesoscopy,” Opt. Lett. 39, 3911–3914 (2014).
[Crossref]

2013 (1)

2012 (1)

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

2011 (2)

2010 (2)

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7, 603–614 (2010).
[Crossref]

J. Eriksson, E. Ollila, and V. Koivunen, “Essential statistics and tools for complex random variables,” IEEE Trans. Signal Process. 58, 5400–5408 (2010).
[Crossref]

2009 (1)

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
[Crossref]

2007 (1)

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99, 184501 (2007).
[Crossref]

2004 (1)

J. D. Müller, “Cumulant analysis in fluorescence fluctuation spectroscopy,” Biophys. J. 86, 3981–3992 (2004).
[Crossref]

2003 (1)

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9, 713–725 (2003).
[Crossref]

Adam, D.

A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
[Crossref]

Allain, M.

Arnal, B.

S. Vilov, B. Arnal, and E. Bossy, “Overcoming the acoustic diffraction limit in photoacoustic imaging by localization of flowing absorbers,” Opt. Lett. 42, 4379–4382 (2017).

B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
[Crossref]

Balabani, S.

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

Baranger, J.

B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
[Crossref]

Bar-Zion, A.

A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
[Crossref]

Baud, O.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Beard, P.

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

J. Brunker and P. Beard, “Acoustic resolution photoacoustic Doppler velocimetry in blood-mimicking fluids,” Sci. Rep. 6, 20902 (2016).
[Crossref]

J. Brunker and P. Beard, “Velocity measurements in whole blood using acoustic resolution photoacoustic Doppler,” Biomed. Opt. Express 7, 2789–2806 (2016).
[Crossref]

P. Beard, “Biomedical photoacoustic imaging,” Interface Focus 1, 602–631 (2011).
[Crossref]

Berer, T.

Bergel, A.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Biran, V.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Bossy, E.

Brunker, J.

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

J. Brunker and P. Beard, “Acoustic resolution photoacoustic Doppler velocimetry in blood-mimicking fluids,” Sci. Rep. 6, 20902 (2016).
[Crossref]

J. Brunker and P. Beard, “Velocity measurements in whole blood using acoustic resolution photoacoustic Doppler,” Biomed. Opt. Express 7, 2789–2806 (2016).
[Crossref]

Bücking, T.

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

Burgholzer, P.

Chaigne, T.

Chen, D.

Choyke, P. L.

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9, 713–725 (2003).
[Crossref]

Cohen, I.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Colyer, R.

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
[Crossref]

Correas, J.-M.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Couture, O.

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Dean-Ben, X. L.

X. L. Dean-Ben and D. Razansky, “Localization optoacoustic tomography,” arXiv:1707.02145 (2017).

Deán-Ben, X. L.

Deffieux, T.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Dellagiacoma, C.

Demene, C.

B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
[Crossref]

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Dertinger, T.

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
[Crossref]

Desailly, Y.

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Ding, L.

Eldar, Y. C.

E. Hojman, T. Chaigne, O. Solomon, S. Gigan, E. Bossy, Y. C. Eldar, and O. Katz, “Photoacoustic imaging beyond the acoustic diffraction-limit with dynamic speckle illumination and sparse joint support recovery,” Opt. Express 25, 4875–4886 (2017).
[Crossref]

A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
[Crossref]

Enderlein, J.

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
[Crossref]

Eriksson, J.

J. Eriksson, E. Ollila, and V. Koivunen, “Essential statistics and tools for complex random variables,” IEEE Trans. Signal Process. 58, 5400–5408 (2010).
[Crossref]

Errico, C.

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Fang, H.

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99, 184501 (2007).
[Crossref]

Franqui, S.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Gateau, J.

Geissbuehler, S.

Gennisson, J.-L.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Gigan, S.

Goodman, J. W.

J. W. Goodman, Speckle Phenomena in Optics: Theory and Applications (Roberts, 2007).

Haltmeier, M.

Hojman, E.

Hu, S.

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

Iyer, G.

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
[Crossref]

Katz, O.

Koivunen, V.

J. Eriksson, E. Ollila, and V. Koivunen, “Essential statistics and tools for complex random variables,” IEEE Trans. Signal Process. 58, 5400–5408 (2010).
[Crossref]

Lasser, T.

Leiss-Holzinger, E.

Lenkei, Z.

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Maslov, K.

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99, 184501 (2007).
[Crossref]

Maslov, K. I.

Y. Zhou, J. Yao, K. I. Maslov, and L. V. Wang, “Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo,” J. Biomed. Opt. 19, 037001 (2014).
[Crossref]

McDonald, D. M.

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9, 713–725 (2003).
[Crossref]

Müller, J. D.

J. D. Müller, “Cumulant analysis in fluorescence fluctuation spectroscopy,” Biophys. J. 86, 3981–3992 (2004).
[Crossref]

Murray, T. W.

Niu, H.

Ntziachristos, V.

M. Omar, D. Soliman, J. Gateau, and V. Ntziachristos, “Ultrawideband reflection-mode optoacoustic mesoscopy,” Opt. Lett. 39, 3911–3914 (2014).
[Crossref]

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7, 603–614 (2010).
[Crossref]

Ollila, E.

J. Eriksson, E. Ollila, and V. Koivunen, “Essential statistics and tools for complex random variables,” IEEE Trans. Signal Process. 58, 5400–5408 (2010).
[Crossref]

Omar, M.

Osmanski, B.-F.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Pernot, M.

B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
[Crossref]

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Pezet, S.

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Pierre, J.

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Razansky, D.

Secomb, T. W.

T. W. Secomb, “Blood flow in the microcirculation,” Annu. Rev. Fluid Mech. 49, 443–461 (2017).
[Crossref]

Sentenac, A.

Sieu, L.-A.

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

Soliman, D.

Solomon, O.

E. Hojman, T. Chaigne, O. Solomon, S. Gigan, E. Bossy, Y. C. Eldar, and O. Katz, “Photoacoustic imaging beyond the acoustic diffraction-limit with dynamic speckle illumination and sparse joint support recovery,” Opt. Express 25, 4875–4886 (2017).
[Crossref]

A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
[Crossref]

Steenbergen, W.

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

Tang, S.

S. Tang and G. Whitesides, “Basic microfluidic and soft lithographic techniques,” in Optofluidics: Fundamentals, Devices and Applications (McGraw-Hill, 2010).

Tanter, M.

B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
[Crossref]

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Tremblay-Darveau, C.

A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
[Crossref]

van den Berg, P.

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

Vilov, S.

Wang, L. V.

Y. Zhou, J. Yao, K. I. Maslov, and L. V. Wang, “Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo,” J. Biomed. Opt. 19, 037001 (2014).
[Crossref]

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

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99, 184501 (2007).
[Crossref]

Wang, X.

Weiss, S.

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
[Crossref]

Whitesides, G.

S. Tang and G. Whitesides, “Basic microfluidic and soft lithographic techniques,” in Optofluidics: Fundamentals, Devices and Applications (McGraw-Hill, 2010).

Yao, J.

Y. Zhou, J. Yao, K. I. Maslov, and L. V. Wang, “Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo,” J. Biomed. Opt. 19, 037001 (2014).
[Crossref]

Yu, B.

Zhou, Y.

Y. Zhou, J. Yao, K. I. Maslov, and L. V. Wang, “Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo,” J. Biomed. Opt. 19, 037001 (2014).
[Crossref]

Annu. Rev. Fluid Mech. (1)

T. W. Secomb, “Blood flow in the microcirculation,” Annu. Rev. Fluid Mech. 49, 443–461 (2017).
[Crossref]

Appl. Opt. (1)

Biomed. Opt. Express (2)

Biophys. J. (1)

J. D. Müller, “Cumulant analysis in fluorescence fluctuation spectroscopy,” Biophys. J. 86, 3981–3992 (2004).
[Crossref]

IEEE Trans. Med. Imaging (2)

A. Bar-Zion, C. Tremblay-Darveau, O. Solomon, D. Adam, and Y. C. Eldar, “Fast vascular ultrasound imaging with enhanced spatial resolution and background rejection,” IEEE Trans. Med. Imaging 36, 169–180 (2017).
[Crossref]

C. Demene, T. Deffieux, M. Pernot, B.-F. Osmanski, V. Biran, J.-L. Gennisson, L.-A. Sieu, A. Bergel, S. Franqui, J.-M. Correas, I. Cohen, O. Baud, and M. Tanter, “Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases Doppler and ultrasound sensitivity,” IEEE Trans. Med. Imaging 34, 2271–2285 (2015).
[Crossref]

IEEE Trans. Signal Process. (1)

J. Eriksson, E. Ollila, and V. Koivunen, “Essential statistics and tools for complex random variables,” IEEE Trans. Signal Process. 58, 5400–5408 (2010).
[Crossref]

Interface Focus (1)

P. Beard, “Biomedical photoacoustic imaging,” Interface Focus 1, 602–631 (2011).
[Crossref]

J. Biomed. Opt. (1)

Y. Zhou, J. Yao, K. I. Maslov, and L. V. Wang, “Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo,” J. Biomed. Opt. 19, 037001 (2014).
[Crossref]

Nat. Med. (1)

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9, 713–725 (2003).
[Crossref]

Nat. Methods (1)

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7, 603–614 (2010).
[Crossref]

Nature (1)

C. Errico, J. Pierre, S. Pezet, Y. Desailly, Z. Lenkei, O. Couture, and M. Tanter, “Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging,” Nature 527, 499–502 (2015).
[Crossref]

Opt. Express (1)

Opt. Lett. (4)

Optica (2)

Phys. Med. Biol. (1)

B. Arnal, J. Baranger, C. Demene, M. Tanter, and M. Pernot, “In vivo real-time cavitation imaging in moving organs,” Phys. Med. Biol. 62, 843–857 (2017).
[Crossref]

Phys. Rev. Lett. (1)

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99, 184501 (2007).
[Crossref]

Proc. Natl. Acad. Sci. USA (1)

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, and J. Enderlein, “Fast, background-free, 3d super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. USA 106, 22287–22292 (2009).
[Crossref]

Proc. SPIE (1)

T. Bücking, P. van den Berg, S. Balabani, W. Steenbergen, P. Beard, and J. Brunker, “Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast,” Proc. SPIE 10064, 100642M (2017).
[Crossref]

Sci. Rep. (1)

J. Brunker and P. Beard, “Acoustic resolution photoacoustic Doppler velocimetry in blood-mimicking fluids,” Sci. Rep. 6, 20902 (2016).
[Crossref]

Science (1)

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

Other (3)

X. L. Dean-Ben and D. Razansky, “Localization optoacoustic tomography,” arXiv:1707.02145 (2017).

S. Tang and G. Whitesides, “Basic microfluidic and soft lithographic techniques,” in Optofluidics: Fundamentals, Devices and Applications (McGraw-Hill, 2010).

J. W. Goodman, Speckle Phenomena in Optics: Theory and Applications (Roberts, 2007).

Supplementary Material (4)

NameDescription
» Supplement 1       Additional theoretical developments, visualisations of imaged samples, description of signal processing and imaging performances analysis
» Visualization 1       Microscope movie of the samples with flowing microspheres
» Visualization 2       Microscope movie of the samples with flowing whole blood (zoom on 1 channel)
» Visualization 3       Microscope movie of the samples with flowing whole blood, area near the input of the circuit with slower flow allows the visualization of single RBC

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Figures (5)

Fig. 1.
Fig. 1.

Numerical results with a vasculature-like phantom. (a) A vessel-like structure (white), with small circulating absorbers (orange). The yellow lines indicate the directions used for the cross sections in (b) and (g). (b) Cross sections along the horizontal yellow line in (a): dashed gray, target structure; red, variance image; blue, 5th-order cumulant; black, horizontal cross section of the main lobe of the PSF [inset in (c)]. (c) Absolute value of the mean PA image, averaged over all acquired images of flowing absorbers. Scale bar: 100 μm. Inset: absolute value of the PSF, |h(r)|. (d) Variance image. Inset: |h2(r)|. (e) Absolute value of 3rd-order cumulant. Inset: |h3(r)|. (f) Absolute value of 5th-order cumulant. Inset: |h5(r)|. (g) Cross sections along the oblique yellow line in (a): dashed gray, target vessel-like structure; red, variance image; blue, 5th-order cumulant.

Fig. 2.
Fig. 2.

Schematic of the experimental setup: parallel microfluidic channels are flown with a water suspension of absorbing particles (Figs. 3 and 4) or whole blood (Fig. 5). The channels are positioned perpendicularly to the imaging plane (orange) of a linear ultrasound array. A pulsed laser beam (green) uniformly illuminates the imaging plane. For each nanosecond laser shot, a PA image is acquired, where the flowing particles appear as a frozen random distribution of absorbers inside the microfluidic channels, providing temporal PA fluctuations from one shot to the next.

Fig. 3.
Fig. 3.

Experimental results. (a) Top-view photograph of the microfluidic circuit, showing the five parallel channels along the (x-z) imaging plane (dashed orange line); see the flow visualization in Fig. S3(a) of Supplement 1. Scale bar: 250 μm. (b) Schematic of the channels with the relevant dimensions. (c) Mean PA image, representing the result of conventional PA imaging. Scale bar: 250 μm. (d) Variance image (2nd-order cumulant). (e) Absolute value of the 3rd-order cumulant. (f) Absolute value of the 6th-order cumulant. (g) One-dimensional profiles across the channels [white dashed line in (c)] for the mean (black), variance (red), 3rd-order (green), and 6th-order (blue) cumulant images. (h) Pulse-echo ultrasound image of the five channels filled with air, illustrating the inability to resolve the structure with conventional imaging. (i)–(k) nth root of the nth-order cumulants for (i) n=2, (j) n=3, and (k) n=6, computed to provide images with comparable units. (l) One-dimensional profiles across the channels for the nth root of the nth-order cumulant images for n=1 (black), n=2 (red), n=3 (green), and n=6 (blue).

Fig. 4.
Fig. 4.

Artifacts elimination via complex cumulant analysis: the axial oscillating artifacts present in conventional SOFI analysis of PA images (a) and (b) are eliminated by extending the SOFI framework to complex cumulants analysis in (c) and (d). (a), (b) 3rd-order real cumulant images of (a) numerical and (b) experimental datasets. Scale bars: 100 μm. (c), (d) 3rd-order complex cumulants (p=1, q=2) of (c) numerical and (d) experimental datasets. (e), (g) Axial profiles along the yellow lines of the (e) simulated images and (g) experimental images for complex cumulant of orders: 1 (black), 2 (red), 3 (green), and 6 (blue). (f), (h) Axial FWHM resolution of the results presented in (e), (g) as a function of complex cumulant order (black dots) together with a fit to the theoretically expected 1/n resolution increase.

Fig. 5.
Fig. 5.

SOFI demonstration using whole human blood at physiological concentration, using 15,100 images. (a) Mean PA image. Scale bar: 100 μm. (b) Microscope picture of the blood flow in the microfluidic channels [see Fig. S3(b) of Supplement 1 for the flow visualization]. Top-right inset: larger magnification. Bottom-right inset: RBCs at the input of the circuit [see Fig. S3(c) of Supplement 1]. Scale bar: 250 μm. (c) 6th-order complex cumulant image. (d) 6th root of the 6th-order complex cumulant image. (e), (f) Corresponding lateral profiles comparing mean (blue), 6th order (red), and microscope profiles (dashed black).

Equations (5)

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αk(r)=f(r)×gk(r).
PAk(r)=[I0×f(r)×gk(r)]*h(r).
Cn(r)=μn(r)k=1n1(n1k1)Ck(r)μnk(r),
Kp,q(r)=mp,q(r)u=1pv=1q1(pu)(q1v)Kpu,qv(r)mu,v(r)v=1q1(q1v)Kp,qv(r)m0,v(r)u=1p(pu)Kpu,q(r)mu,0(r).
Kp,0(r)=mp,0(r)u=1p1(p1u1)Ku,0(r)mpu,0(r),