Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Photoacoustically guided wavefront shaping for enhanced optical focusing in scattering media

Abstract

Non-invasively focusing light into strongly scattering media, such as biological tissue, is highly desirable but challenging. Recently, ultrasonically guided wavefront-shaping technologies have been developed to address this limitation. So far, the focusing resolution of most implementations has been limited by acoustic diffraction. Here, we introduce nonlinear photoacoustically guided wavefront shaping (PAWS), which achieves optical diffraction-limited focusing in scattering media. We develop an efficient dual-pulse excitation approach to generate strong nonlinear photoacoustic signals based on the Grueneisen relaxation effect. These nonlinear photoacoustic signals are used as feedback to guide iterative wavefront optimization. As a result, light is effectively focused to a single optical speckle grain on the scale of 5–7 μm, which is 10 times smaller than the acoustic focus, with an enhancement factor of 6,000 in peak fluence. This technology has the potential to benefit many applications that require a highly confined strong optical focus in tissue.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Principles.
Figure 2: Experimental set-up and dual-stage optimization.
Figure 3: Experimental results of stage 1: using a linear photoacoustic signal as feedback for wavefront shaping (linear PAWS).
Figure 4: Experimental results of stage 2: using a nonlinear photoacoustic signal as feedback for wavefront shaping (nonlinear PAWS).
Figure 5: Visualization of single speckle grain focusing using nonlinear PAWS.

Similar content being viewed by others

References

  1. Bohren, C. F. & Huffman, D. R. Absorption and Scattering of Light by Small Particles (Wiley, 1998).

    Book  Google Scholar 

  2. Wang, L. V. & Wu, H.-I. Biomedical Optics: Principles and Imaging (John Wiley & Sons, 2007).

    Google Scholar 

  3. Fenno, L., Yizhar, O. & Deisseroth, K. The development and application of optogenetics. Ann. Rev. Neurosci. 34, 389–412 (2011).

    Article  Google Scholar 

  4. Galanzha, E. I. et al. In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles. J. Biophoton. 2, 528–539 (2009).

    Article  Google Scholar 

  5. Vellekoop, I. M. & Mosk, A. P. Focusing coherent light through opaque strongly scattering media. Opt. Lett. 32, 2309–2311 (2007).

    Article  ADS  Google Scholar 

  6. Xu, X., Liu, H. & Wang, L. V. Time-reversed ultrasonically encoded optical focusing into scattering media. Nature Photon. 5, 154–157 (2011).

    Article  ADS  Google Scholar 

  7. Liu, H., Xu, X., Lai, P. & Wang, L. V. Time-reversed ultrasonically encoded (TRUE) optical focusing into tissue-mimicking media with optical thickness up to 70 mean free paths. J. Biomed. Opt. 16, 086009 (2011).

    Article  ADS  Google Scholar 

  8. Lai, P., Xu, X., Liu, H., Suzuki, Y. & Wang, L. V. Reflection-mode time-reversed ultrasonically encoded (TRUE) optical focusing into turbid media. J. Biomed. Opt. 16, 080505 (2011).

    Article  ADS  Google Scholar 

  9. Lai, P., Xu, X., Liu, H. & Wang, L. V. Time-reversed ultrasonically encoded (TRUE) optical focusing in biological tissue. J. Biomed. Opt. 17, 030506 (2012).

    Article  ADS  Google Scholar 

  10. Suzuki, Y., Xu, X., Lai, P. & Wang, L. V. Energy enhancement in time-reversed ultrasonically encoded optical focusing using a photorefractive polymer. J. Biomed. Opt. 17, 080507 (2012).

    Article  ADS  Google Scholar 

  11. Lai, P., Suzuki, Y., Xu, X. & Wang, L. V. Focused fluorescence excitation with time-reversed ultrasonically encoded light and imaging in thick scattering media. Laser Phys. Lett. 10, 075604 (2013).

    Article  ADS  Google Scholar 

  12. Wang, Y. M., Judkewitz, B., DiMarzio, C. A. & Yang, C. Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light. Nature Commun. 3, 928 (2012).

    Article  ADS  Google Scholar 

  13. Si, K., Fiolka, R. & Cui, M. Fluorescence imaging beyond the ballistic regime by ultrasound-pulse-guided digital phase conjugation. Nature Photon. 6, 657–661 (2012).

    Article  ADS  Google Scholar 

  14. Judkewitz, B., Wang, Y. M., Horstmeyer, R., Mathy, A. & Yang, C. Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE). Nature Photon. 7, 300–305 (2013).

    Article  ADS  Google Scholar 

  15. Hsieh, C.-L., Pu, Y., Grange, R. & Psaltis, D. Digital phase conjugation of second harmonic radiation emitted by nanoparticles in turbid media. Opt. Express 18, 12283–12290 (2010).

    Article  ADS  Google Scholar 

  16. Vellekoop, I. M., Cui, M. & Yang, C. Digital optical phase conjugation of fluorescence in turbid tissue. Appl. Phys. Lett. 101, 081108 (2012).

    Article  ADS  Google Scholar 

  17. Vellekoop, I. M. & Mosk, A. P. Phase control algorithms for focusing light through turbid media. Opt. Commun. 281, 3071–3080 (2008).

    Article  ADS  Google Scholar 

  18. Cui, M. Parallel wavefront optimization method for focusing light through random scattering media. Opt. Lett. 36, 870–872 (2011).

    Article  ADS  Google Scholar 

  19. Conkey, D. B., Brown, A. N., Caravaca-Aguirre, A. M. & Piestun, R. Genetic algorithm optimization for focusing through turbid media in noisy environments. Opt. Express 20, 4840–4849 (2012).

    Article  ADS  Google Scholar 

  20. Popoff, S. M. et al. Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media. Phys. Rev. Lett. 104, 100601 (2010).

    Article  ADS  Google Scholar 

  21. Kong, F. et al. Photoacoustic-guided convergence of light through optically diffusive media. Opt. Lett. 36, 2053–2055 (2011).

    Article  ADS  Google Scholar 

  22. Caravaca-Aguirre, A. M. et al. High contrast three-dimensional photoacoustic imaging through scattering media by localized optical fluence enhancement. Opt. Express 21, 26671–26676 (2013).

    Article  ADS  Google Scholar 

  23. Conkey, D. B. et al. Super-resolution photoacoustic imaging through a scattering wall. Preprint at http://arXiv.org/abs/1310.5736 (2013).

  24. Chaigne, T. et al. Improving photoacoustic-guided optical focusing in scattering media by spectrally filtered detection. Opt. Lett. 39, 6054–6057 (2014).

    Article  ADS  Google Scholar 

  25. Chaigne, T. et al. Controlling light in scattering media noninvasively using the photo-acoustic transmission-matrix. Nature Photon. 8, 58–64 (2014).

    Article  ADS  Google Scholar 

  26. Yao, J., Ke, H., Tai, S., Zhou, Y. & Wang, L. V. Absolute photoacoustic thermometry in deep tissue. Opt. Lett. 38, 5228–5231 (2013).

    Article  ADS  Google Scholar 

  27. Katz, O., Small, E., Broomberg, Y. & Silberberg, Y. Focusing and compression of ultrashort pulses through scattering media. Nature Photon. 5, 372–377 (2011).

    Article  ADS  Google Scholar 

  28. Tay, J. W., Lai, P., Suzuki, Y. & Wang, L. V. Ultrasonically encoded wavefront shaping for focusing into random media. Sci. Rep. 4, 3918 (2014).

    Article  ADS  Google Scholar 

  29. Hepler, L. G. Thermal expansion and structure in water and aqueous solutions. Can. J. Chem. 47, 4613–4617 (1969).

    Article  Google Scholar 

  30. Wang, S.-H., Wei, C.-W., Jee, S.-H. & Li, P.-C. Quantitative thermal imaging for plasmonic photothermal therapy. J. Med. Biol. Eng. 31, 387–393 (2011).

    Article  Google Scholar 

  31. Duck, F. A. Physical Properties of Tissue (Academic, 1990).

    Google Scholar 

  32. Mosk, A. P., Lagendijk, A., Lerosey, G. & Fink, M. Controlling waves in space and time for imaging and focusing in complex media. Nature Photon. 6, 283–292 (2012).

    Article  ADS  Google Scholar 

  33. Conkey, D. B., Caravaca-Aguirre, A. M. & Piestun, R. High-speed scattering medium characterization with application to focusing light through turbid media. Opt. Express 20, 1733–1740 (2012).

    Article  ADS  Google Scholar 

  34. American National Standard for the Safe Use of Laser in Health Care Facilities, ANSI Z1361.1 (American National Standards Institute, 2000).

  35. Petrova, E. et al. Using optoacoustic imaging for measuring the temperature dependence of Grueneisen parameter in optically absorbing solutions. Opt. Express 21, 25077–25090 (2013).

    Article  ADS  Google Scholar 

  36. Tay, J. W., Taylor, M. A. & Bowen, W. P. Sagnac-interferometer-based characterization of spatial light modulators. Appl. Opt. 48, 2236–2242 (2009).

    Article  ADS  Google Scholar 

  37. Piederrière, Y. et al. Scattering through fluids: speckle size measurement and Monte Carlo simulations close to and into the multiple scattering. Opt. Express 12, 176–188 (2004).

    Article  ADS  Google Scholar 

  38. Kolosov, O. V., Lobkis, O. I., Maslov, K. I. & Zinin, P. V. The effect of the focal plane position on image of spherical object in the reflection acoustic microscope. Acoust. Lett. 16, 84–88 (1992).

    Google Scholar 

  39. Maslov, K. I., Dorozhkin, L. M., Doroshenko, V. S. & Maev, R. G. A new focusing ultrasonic transducer and two foci acoustic lens for acoustic microscopy. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 44, 380–385 (1997).

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank K. Maslov for manufacturing the acoustic lens, C. Ma for assistance with acoustic focus calibration, T.-W. Wong for help with preparing the supplementary cartoons and J. Ballard for editing the manuscript. This work was sponsored in part by National Institutes of Health grants DP1 EB016986 (NIH Director's Pioneer Award) and R01 CA186567 (NIH Director's Transformative Research Award) as well as National Academies Keck Futures Initiative grant IS 13.

Author information

Authors and Affiliations

Authors

Contributions

P.L., J.W.T. and L.V.W. initiated the project. P.L. implemented the photoacoustically guided wavefront-shaping system. L.W. initiated the principle of dual-pulse photoacoustic nonlinearity based on the Grueneisen relaxation effect. J.W.T. wrote code for the experiment and simulations. P.L., J.W.T. and L.W. designed and ran the experiment, and prepared the manuscript. L.V.W. provided overall supervision. All authors were involved in analysis of the results and revision of the manuscript.

Corresponding author

Correspondence to Lihong V. Wang.

Ethics declarations

Competing interests

P.L., J.W.T. and L.W. declare no competing financial interests. L.V.W. has financial interests in Microphotoacoustics, Inc. and Endra, Inc., which, however, did not support this work.

Supplementary information

Supplementary information

Supplementary information (PDF 524 kb)

Supplementary movie 1

Supplementary movie 1 (WMV 2231 kb)

Supplementary movie 2

Supplementary movie 2 (WMV 1395 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lai, P., Wang, L., Tay, J. et al. Photoacoustically guided wavefront shaping for enhanced optical focusing in scattering media. Nature Photon 9, 126–132 (2015). https://doi.org/10.1038/nphoton.2014.322

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nphoton.2014.322

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing