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

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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Figure 1: Schematics of the SIP-PACT system.
Figure 2: Label-free SIP-PACT of small-animal whole-body anatomy from the brain to the trunk.
Figure 3: Label-free imaging of small-animal whole-body dynamics.
Figure 4: SIP-PACT of mouse whole-body oxygenation dynamics.
Figure 5: Label-free tracking of CTCs in the mouse brain in vivo.
Figure 6: Deep imaging of rat whole-brain functions and whole-body anatomy.

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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

Affiliations

Authors

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.

Corresponding author

Correspondence to Lihong V. Wang.

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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.

Supplementary information

Supplementary Information

Supplementary figures, tables, references and video captions. (PDF 17806 kb)

Supplementary Video 1

In vivo label-free photoacoustic computed tomography of mouse internal organs. (MP4 47735 kb)

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. (MP4 18496 kb)

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. (MP4 14849 kb)

Supplementary Video 4

In vivo label-free photoacoustic computed tomography of a mouse's whole-body anatomy at a cross-section of the liver. (MP4 5966 kb)

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. (MP4 6368 kb)

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. (MP4 13612 kb)

Supplementary Video 7

In vivo cross-sectional images of the mouse liver reconstructed by increasing angular coverage. (MP4 237 kb)

Supplementary Video 8

Pulse-wave-induced cross-sectional-area changes of two vertical arteries over time. (MP4 1761 kb)

Supplementary Video 9

In vivo label-free photoacoustic computed tomography of the mouse brain in response to an oxygen challenge. (MP4 3395 kb)

Supplementary Video 10

Oxygenation response of the lower abdominal cavity of a mouse during whole-body oxygen challenge. (MP4 7848 kb)

Supplementary Video 11

Label-free tracking of circulating melanoma tumour cells in the mouse brain in vivo. (MP4 8069 kb)

Supplementary Video 12

In vivo monitoring of dye perfusion in the mouse brain. (MP4 955 kb)

Supplementary Video 13

In vivo label-free photoacoustic computed tomography of rat whole-body anatomy at a cross-section of the lower abdominal cavity. (MP4 3008 kb)

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Li, L., Zhu, L., Ma, C. et al. Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution. Nat Biomed Eng 1, 0071 (2017). https://doi.org/10.1038/s41551-017-0071

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