Article

Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution

  • Nature Biomedical Engineering 1, Article number: 0071 (2017)
  • doi:10.1038/s41551-017-0071
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Abstract

Imaging of small animals has played an indispensable role in preclinical research by providing high-dimensional physiological, pathological and phenotypic insights with clinical relevance. Yet, pure optical imaging suffers from either shallow penetration (up to ~1–2 mm) or a poor depth-to-resolution ratio (~3), and non-optical techniques for whole-body imaging of small animals lack either spatiotemporal resolution or functional contrast. Here, we demonstrate that stand-alone single-impulse panoramic photoacoustic computed tomography (SIP-PACT) mitigates these limitations by combining high spatiotemporal resolution (125 μm in-plane resolution, 50 μs per frame data acquisition and 50 Hz frame rate), deep penetration (48 mm cross-sectional width in vivo), anatomical, dynamical and functional contrasts, and full-view fidelity. Using SIP-PACT, we imaged in vivo whole-body dynamics of small animals in real time and obtained clear sub-organ anatomical and functional details. We tracked unlabelled circulating melanoma cells and imaged the vasculature and functional connectivity of whole rat brains. SIP-PACT holds great potential for both preclinical imaging and clinical translation.

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Acknowledgements

We thank Y. He, C. Li, Y. Li and J. Xia for their technical support, and J. Ballard for close reading of the manuscript. This work was sponsored by the United States National Institutes of Health (NIH) grants DP1 EB016986 (NIH Director’s Pioneer Award), R01 CA186567 (NIH Director’s Transformative Research Award), U01 NS090579 (BRAIN Initiative), U01 NS099717 (BRAIN Initiative), R01 EB016963 and S10 RR026922.

Author information

Author notes

    • Cheng Ma
    • , Junjie Yao
    •  & Lidai Wang

    Present addresses: Department of Electronic Engineering, Tsinghua University, Beijing 100084, China (C.M.); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA (J.Y.); Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong, China (L.W.)

    • Lei Li
    • , Liren Zhu
    • , Cheng Ma
    •  & Li Lin

    These authors contributed equally to this work.

Affiliations

  1. Department of Electrical and Systems Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, USA.

    • Lei Li
  2. Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.

    • Lei Li
    • , Liren Zhu
    • , Li Lin
    • , Konstantin Maslov
    • , Junhui Shi
    •  & Lihong V. Wang
  3. Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, USA.

    • Liren Zhu
    • , Cheng Ma
    • , Li Lin
    • , Junjie Yao
    • , Lidai Wang
    • , Ruiying Zhang
    •  & Wanyi Chen
  4. Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.

    • Cheng Ma
    •  & Lihong V. Wang

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Contributions

L.Li and L.V.W. conceived and designed the study. L.Li and L.Z. constructed the hardware system. L.Li, L.Z. and C.M. developed the software system and the reconstruction algorithm. L.W. and J.S. constructed the control program. K.M. and W.C. designed the preamplifiers. L.Li, C.M. and L.Lin performed the experiments. R.Z. cultured the B16 cells. L.Li, L.Z., C.M. and J.Y. analysed the data. L.V.W. supervised the study. All authors contributed to the writing of the manuscript.

Competing interests

L.V.W. and K.M. have a financial interest in Microphotoacoustics, Inc.; however, Microphotoacoustics, Inc. did not support this work. The other authors declare no competing financial interests.

Corresponding author

Correspondence to Lihong V. Wang.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary figures, tables, references and video captions.

Videos

  1. 1.

    Supplementary Video 1

    In vivo label-free photoacoustic computed tomography of mouse internal organs.

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    Supplementary Video 2

    In vivo label-free photoacoustic computed tomography of a mouse's whole-body anatomy at a cross-section of the upper thoracic cavity.

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    Supplementary Video 3

    In vivo label-free photoacoustic computed tomography of mouse's whole-body anatomy at a cross-section of the lower thoracic cavity.

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    Supplementary Video 4

    In vivo label-free photoacoustic computed tomography of a mouse's whole-body anatomy at a cross-section of the liver.

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    Supplementary Video 5

    In vivo label-free photoacoustic computed tomography of a mouse's whole-body anatomy at a cross-section of the upper abdominal cavity.

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    Supplementary Video 6

    In vivo label-free photoacoustic computed tomography of a mouse's whole-body anatomy at a cross-section of the lower abdominal cavity.

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    Supplementary Video 7

    In vivo cross-sectional images of the mouse liver reconstructed by increasing angular coverage.

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    Supplementary Video 8

    Pulse-wave-induced cross-sectional-area changes of two vertical arteries over time.

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    Supplementary Video 9

    In vivo label-free photoacoustic computed tomography of the mouse brain in response to an oxygen challenge.

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    Supplementary Video 10

    Oxygenation response of the lower abdominal cavity of a mouse during whole-body oxygen challenge.

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    Supplementary Video 11

    Label-free tracking of circulating melanoma tumour cells in the mouse brain in vivo.

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    Supplementary Video 12

    In vivo monitoring of dye perfusion in the mouse brain.

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    Supplementary Video 13

    In vivo label-free photoacoustic computed tomography of rat whole-body anatomy at a cross-section of the lower abdominal cavity.