Skip to main content

Thank you for visiting 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.

Snapshot photoacoustic topography through an ergodic relay for high-throughput imaging of optical absorption


Current embodiments of photoacoustic imaging require either serial detection with a single-element ultrasonic transducer or parallel detection with an ultrasonic array, necessitating a trade-off between cost and throughput. Here, we present photoacoustic topography through an ergodic relay (PATER) for low-cost high-throughput snapshot wide-field imaging. Encoding spatial information with randomized temporal signatures through ergodicity, PATER requires only a single-element ultrasonic transducer to capture a wide-field image with a single laser shot. We applied PATER to demonstrate both functional imaging of haemodynamic responses and high-speed imaging of blood pulse wave propagation in mice in vivo. Leveraging the high frame rate of 2 kHz, PATER tracked and localized moving melanoma tumour cells in the mouse brain in vivo, which enabled flow velocity quantification and super-resolution imaging. Among the potential biomedical applications of PATER, wearable devices to monitor human vital signs in particular is envisaged.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Imaging mechanism of PATER.
Fig. 2: Schematic of the PATER system.
Fig. 3: Mouse brain haemoglobin responses to front-paw stimulations.
Fig. 4: Quantification of blood pulse wave velocity.
Fig. 5: Localization and tracking of MTCs in the mouse brain at super-resolution.

Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request and with permission from corporate collaborations.

Code availability

The reconstruction algorithm and data processing methods are described in detail in the Methods. We have opted not to make the computer codes publicly available owing to corporate collaborations and pending patent applications.


  1. 1.

    Juskaitis, R., Wilson, T., Neil, M. M. A. & Kozubek, M. Efficient real-time confocal microscopy with white light sources. Nature 383, 804–806 (1996).

    ADS  Google Scholar 

  2. 2.

    Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    ADS  Google Scholar 

  3. 3.

    Horton, N. G. et al. In vivo three-photon microscopy of subcortical structures within an intact mouse brain. Nat. Photon. 7, 205–209 (2013).

    ADS  Google Scholar 

  4. 4.

    Vakoc, B. J., Fukumura, D., Jain, R. K. & Bouma, B. E. Cancer imaging by optical coherence tomography: preclinical progress and clinical potential. Nat. Rev. Cancer 12, 363–368 (2012).

    Google Scholar 

  5. 5.

    Etoh, T. G. et al. An image sensor which captures 100 consecutive frames at 1000000 frames/s. IEEE Trans. Electron. Dev. 50, 144–151 (2003).

    ADS  Google Scholar 

  6. 6.

    Gao, L., Liang, J., Li, C. & Wang, L. V. Single-shot compressed ultrafast photography at one hundred billion frames per second. Nature 516, 74–77 (2014).

    ADS  Google Scholar 

  7. 7.

    Wu, H. et al. Eulerian video magnification for revealing subtle changes in the world. ACM Trans. Graphics 31, 1–8 (2012).

    Google Scholar 

  8. 8.

    Bouchard, M. B., Chen, B. R., Burgess, S. A. & Hillman, E. M. C. Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics. Opt. Express 17, 15670–15678 (2009).

    ADS  Google Scholar 

  9. 9.

    Wang, L. V. & Hu, S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science 335, 1458–1462 (2012).

    ADS  Google Scholar 

  10. 10.

    Jathoul, A. P. et al. Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter. Nat. Photon. 9, 239–246 (2015).

    ADS  Google Scholar 

  11. 11.

    Taruttis, A. & Ntziachristos, V. Advances in real-time multispectral optoacoustic imaging and its applications. Nat. Photon. 9, 219–227 (2015).

    ADS  Google Scholar 

  12. 12.

    Wang, L. V. & Yao, J. A practical guide to photoacoustic tomography in the life sciences. Nat. Methods 13, 627–638 (2016).

    Google Scholar 

  13. 13.

    Li, L. et al. Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution. Nat. Biomed. Eng. 1, 0071 (2017).

    Google Scholar 

  14. 14.

    Deán-Ben, X. L. & Razansky, D. Adding fifth dimension to optoacoustic imaging: volumetric time-resolved spectrally enriched tomography. Light Sci. Appl. 3, e137 (2014).

    Google Scholar 

  15. 15.

    Yao, J. et al. Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe. Nat. Methods 13, 67–73 (2015).

    Google Scholar 

  16. 16.

    Gamelin, J. et al. A real-time photoacoustic tomography system for small animals. Opt. Express 17, 10489–10498 (2009).

    ADS  Google Scholar 

  17. 17.

    Wong, T. T. W. et al. Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy. Nat. Commun. 8, 1386 (2017).

    ADS  Google Scholar 

  18. 18.

    Li, L. et al. Label-free photoacoustic tomography of whole mouse brain structures ex vivo. Neurophotonics 3, 035001 (2016).

    Google Scholar 

  19. 19.

    Wang, L. V. Multiscale photoacoustic microscopy and computed tomography. Nat. Photon. 3, 503–509 (2009).

    ADS  Google Scholar 

  20. 20.

    Draeger, C. & Fink, M. One-channel time reversal of elastic waves in a chaotic 2D-silicon cavity. Phys. Rev. Lett. 79, 407–410 (1997).

    ADS  Google Scholar 

  21. 21.

    Ing, R. K., Quieffin, N., Catheline, S. & Fink, M. In solid localization of finger impacts using acoustic time-reversal process. Appl. Phys. Lett. 87, 204104 (2005).

    ADS  Google Scholar 

  22. 22.

    Cox, B. & Beard, P. C. Photoacoustic tomography with a single detector in a reverberant cavity. J. Acoustical Soc. Am. 125, 1426–1436 (2009).

    ADS  Google Scholar 

  23. 23.

    Wang, L. V. Photo acoustic tomography. Scholarpedia 9, 10278 (2014).

    ADS  Google Scholar 

  24. 24.

    Beard, P. C. Biomedical photoacoustic imaging. Interface Focus 1, 602–631 (2011).

    Google Scholar 

  25. 25.

    Treeby, B. & Cox, B. k-Wave: MATLAB toolbox for the simulation and reconstruction of photoacoustic wave-fields. J. Biomed. Opt. 15, 021314 (2010).

    ADS  Google Scholar 

  26. 26.

    Yao, J. et al. High-speed label-free functional photoacoustic microscopy of mouse brain in action. Nat. Methods 12, 407–410 (2015).

    Google Scholar 

  27. 27.

    Liao, L. D. et al. Transcranial imaging of functional cerebral hemodynamic changes in single blood vessels using in vivo photoacoustic microscopy. J. Cerebral Blood Flow Metabolism 2, 938–951 (2012).

    Google Scholar 

  28. 28.

    Hai, P., Yao, J., Maslov, K., Zhou, Y. & Wang, L. V. Near-infrared optical-resolution photoacoustic microscopy. Opt. Lett. 39, 5192–5195 (2014).

    ADS  Google Scholar 

  29. 29.

    Hsu, H.-C. et al. Dual-axis illumination for virtually augmenting the detection view of optical-resolution photoacoustic microscopy. J. Biomed. Opt. 23, 076001 (2018).

    ADS  Google Scholar 

  30. 30.

    Georgianos, P. I., Pikilidou, M. I., Liakopoulos, V., Balaska, E. V. & Zebekakis, P. E. Arterial stiffness in end-stage renal disease—pathogenesis, clinical epidemiology, and therapeutic potentials. Hypertension Res. 41, 309–319 (2018).

    Google Scholar 

  31. 31.

    London, G. M. & Guerin, A. P. Influence of arterial pulse and reflected waves on blood pressure and cardiac function. Am. Heart J. 138, S220–S224 (1999).

    Google Scholar 

  32. 32.

    Yeh, C., Hu, S., Maslov, K. & Wang, L. V. Photoacoustic microscopy of blood pulse wave. J. Biomed. Opt. 17, 070504 (2012).

    ADS  Google Scholar 

  33. 33.

    Fitch, R. M., Vergona, R., Sullivan, M. E. & Wang, Y.-X. Nitric oxide synthase inhibition increases aortic stiffness measured by pulse wave velocity in rats. Cardiovasc. Res. 51, 351–358 (2001).

    Google Scholar 

  34. 34.

    Seki, J. Flow pulsation and network structure in mesenteric microvasculature of rats. Am. J. Physiol. Heart Circulatory Physiol. 266, H811–H821 (1994).

    Google Scholar 

  35. 35.

    Miura, G. Cancer tumor imaging: catch me if you can. Nat. Chem. Biol. 10, 485 (2014).

    ADS  Google Scholar 

  36. 36.

    Hai, P. et al. Label-free high-throughput detection and quantification of circulating melanoma tumor cell clusters by linear-array-based photoacoustic tomography. J. Biomed. Opt. 22, 041004 (2017).

    ADS  Google Scholar 

  37. 37.

    Dean-Ben, X. L. & Razansky, D. Localization optoacoustic tomography. Light Sci. Appl. 7, 18004 (2018).

    Google Scholar 

  38. 38.

    Liang, Y., Jin, L., Guan, B.-O. & Wang, L. 2 MHz multi-wavelength pulsed laser for functional photoacoustic microscopy. Opt. Lett. 42, 1452–1455 (2017).

    ADS  Google Scholar 

  39. 39.

    Li, L. et al. Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo. Nat. Commun. 9, 2734 (2018).

    ADS  Google Scholar 

  40. 40.

    Wu, Z. et al. A microrobotic system guided by photoacoustic computed tomography for targeted navigation in intestines in vivo. Sci. Robot. 4, eaax0613 (2019).

    Google Scholar 

  41. 41.

    Moderne Messmethoden der Physik Vol. 1, 2, Extended edition (Deutscher Verlag der Wissenschaften, 1960).

  42. 42.

    Laser Institute of America. American National Standard for safe use of lasers (American National Standards Institute, 2000).

  43. 43.

    Bioucas-Dias, J. M. & Figueiredo, M. A. T. A new TwIST: two-step iterative shrinkage/thresholding algorithms for image restoration. IEEE Trans. Image Processing 16, 2992–3004 (2007).

    ADS  MathSciNet  Google Scholar 

  44. 44.

    Jacobs, J. D. & Hopper-Borge, E. A. Carotid artery infusions for pharmacokinetic and pharmacodynamic analysis of taxanes in mice. J. Vis. Exp. 92, e51917 (2014).

    Google Scholar 

  45. 45.

    Winkler, A. M., Maslov, K. & Wang, L. V. Noise-equivalent sensitivity of photoacoustics. J. Biomed. Opt. 18, 097003 (2013).

    Google Scholar 

  46. 46.

    Thompson, R. E., Larson, D. R. & Webb, W. W. Precise nanometer localization analysis for individual fluorescent probes. Biophys. J. 82, 2775–2783 (2002).

    Google Scholar 

Download references


We thank J. Ballard and C. Ma for close reading of the manuscript, Y. He and C. Yeh for technical support, and P. Hai for his image superposition codes. This work was sponsored by National Institutes of Health Grants DP1 EB016986 (NIH Director’s Pioneer Award), R01 CA186567 (NIH Director’s Transformative Research Award), R01 EB016963, U01 NS090579 (NIH BRAIN Initiative) and U01 NS099717 (NIH BRAIN Initiative).

Author information




Y.L. and L.L. designed the study. Y.L., L.L. and K.M. built the imaging system. L.L. and Y.L. planned the experiments. Y.L., L.L., E.B. and J.Y. performed the experiments. J.S. and L.W. developed the data acquisition program. L.Z., Y.L. and L.L. developed the reconstruction algorithm. Y.L., L.L., L.Z., J.L., P.H. and J.Y. analysed the data. L.V.W. conceived the concept and supervised the project. All authors contributed to writing the manuscript.

Corresponding author

Correspondence to Lihong V. Wang.

Ethics declarations

Competing interests

L.V.W. and K.M. have financial interests in Microphotoacoustics, Inc., CalPACT, LLC and Union Photoacoustic Technologies, Ltd, which did not support this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figs. 1–10 and Supplementary Notes 1–4.

Reporting Summary

Supplementary Video 1

Demonstration of PATER’s imaging mechanism.

Supplementary Video 2

Quantification of the spatial resolution of snapshot wide-field imaging by PATER.

Supplementary Video 3

Snapshot wide-field imaging by PATER of blood flow behind biological tissue.

Supplementary Video 4

Snapshot wide-field functional PATER imaging of haemoglobin responses in a mouse brain to front-paw stimulations in vivo.

Supplementary Video 5

Visualization of blood pulse wave propagation in the middle cerebral arteries.

Supplementary Video 6

Snapshot wide-field tracking of MTCs in a tube using PATER at 660 nm light illumination.

Supplementary Video 7

Snapshot wide-field tracking of MTCs in a mouse brain in vivo using PATER at 660 nm light illumination.

Supplementary Video 8

Close-up slow-motion video of snapshot wide-field tracking of MTCs as shown in Supplementary Video 6.

Supplementary Video 9

Buildup of MTC localization map. The positions of migrating MTCs in the blood vessels were tracked throughout the video from Supplementary Video 6 and superimposed.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Li, L., Zhu, L. et al. Snapshot photoacoustic topography through an ergodic relay for high-throughput imaging of optical absorption. Nat. Photonics 14, 164–170 (2020).

Download citation

Further reading


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