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Massively parallel functional photoacoustic computed tomography of the human brain

Abstract

Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging of the human brain requires bulky equipment for the generation of magnetic fields. Photoacoustic computed tomography obviates the need for magnetic fields by using light and sound to measure deoxyhaemoglobin and oxyhaemoglobin concentrations to then quantify oxygen saturation and blood volumes. Yet, the available imaging speeds, fields of view (FOV), sensitivities and penetration depths have been insufficient for functional imaging of the human brain. Here, we show that massively parallel ultrasonic transducers arranged hemispherically around the human head can produce tomographic images of the brain with a 10-cm-diameter FOV and spatial and temporal resolutions of 350 µm and 2 s, respectively. In patients who had a hemicraniectomy, a comparison of functional photoacoustic computed tomography and 7 T BOLD functional magnetic resonance imaging showed a strong spatial correspondence in the same FOV and a high temporal correlation between BOLD signals and photoacoustic signals, with the latter enabling faster detection of functional activation. Our findings establish the use of photoacoustic computed tomography for human brain imaging.

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Fig. 1: Representations of the 1K3D-fPACT.
Fig. 2: PACT angiography and MRA of the same brains.
Fig. 3: Evaluating the 1K3D-fPACT for brain function mapping using 7 T fMRI and motor tasks.
Fig. 4: Imaging language processing.
Fig. 5: Measuring brain function in a participant who experienced discomfort in MRI due to implants.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. 3D functional image stacks of fMRI and fPACT for participant 3 (FT and LP session 1) are available online (https://doi.org/10.5061/dryad.sxksn0310). Other data are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request.

Code availability

The fMRI data were processed using the freely available software package SPM12. The codes used to extract the fPACT function are available online (https://doi.org/10.5281/zenodo.4615721). The reconstruction codes based on the universal backprojection algorithm, the system control software and the data collection software are proprietary and used in licensed technologies, yet they are available from the corresponding authors on reasonable request.

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Acknowledgements

We thank G. Corral-Leyva for patient care and Y. Luo for discussion on the potential of artificial intelligence in advancing PACT. This work was sponsored by the US National Institutes of Health (NIH) grants R35 CA220436 (Outstanding Investigator Award), U01 NS099717 (BRAIN Initiative), R01 NS102213, R01 NS114382 and R01 EB028297, and by Caltech internal funds (PPF0021).

Author information

Authors and Affiliations

Authors

Contributions

L.V.W., C.Y.L., S.N. and J.J.R. conceived the project. S.N., J.J.R., C.Y.L. and L.V.W. designed the study. L.L., S.N., K.M. and J.S. built the system hardware. S.N. developed the system software. S.N., X.Y. and J.J.R. performed the PACT experiments. K.B.J. and L.Y. performed the MRI experiments. P.H., X.Y. and S.N. developed the reconstruction algorithms. X.Y., S.N., K.B.J., J.J.R., C.Y.L., D.J.W. and L.V.W. analysed and interpreted the data. J.J.R. and C.Y.L. recruited the participants. S.N., J.J.R. and X.Y. wrote the manuscript with input from all of the authors. L.V.W., C.Y.L. and D.J.W. supervised the study.

Corresponding authors

Correspondence to Charles Y. Liu or Lihong V. Wang.

Ethics declarations

Competing interests

L.V.W. has a financial interest in Microphotoacoustics Inc., CalPACT LLC and Union Photoacoustic Technologies Ltd., which, however, did not support this work. K.M. has a financial interest in Microphotoacoustics, Inc. The other authors declare no competing interests.

Additional information

Peer review information Nature Biomedical Engineering thanks the anonymous reviewers for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary methods, figures, tables, video captions and references.

Reporting Summary

Supplementary Video 1

Comparisons of the angiographic structures and functional maps acquired on 7 T MRI and the 1K3D-fPACT for participant 1.

Supplementary Video 2

Comparisons of the angiographic structures and functional maps acquired on 7 T MRI and the 1K3D-fPACT for participant 3.

Supplementary Video 3

Participant 1 being imaged by the 1K3D-fPACT when performing the finger-tapping task.

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Na, S., Russin, J.J., Lin, L. et al. Massively parallel functional photoacoustic computed tomography of the human brain. Nat. Biomed. Eng 6, 584–592 (2022). https://doi.org/10.1038/s41551-021-00735-8

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