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Published May 29, 2024 | Published
Journal Article Open

Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window

Rabut, Claire ORCID icon
Norman, Sumner L. ORCID icon
Griggs, Whitney S. ORCID icon
Russin, Jonathan J. ORCID icon
Jann, Kay ORCID icon
Christopoulos, Vasileios
Liu, Charles ORCID icon
Andersen, Richard A.1 ORCID icon
Shapiro, Mikhail G.1 ORCID icon
  • 1. ROR icon California Institute of Technology

Abstract

Visualization of human brain activity is crucial for understanding normal and aberrant brain function. Currently available neural activity recording methods are highly invasive, have low sensitivity, and cannot be conducted outside of an operating room. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging; however, fUSI cannot be performed through the adult human skull. Here, we used a polymeric skull replacement material to create an acoustic window compatible with fUSI to monitor adult human brain activity in a single individual. Using an in vitro cerebrovascular phantom to mimic brain vasculature and an in vivo rodent cranial defect model, first, we evaluated the fUSI signal intensity and signal-to-noise ratio through polymethyl methacrylate (PMMA) cranial implants of different thicknesses or a titanium mesh implant. We found that rat brain neural activity could be recorded with high sensitivity through a PMMA implant using a dedicated fUSI pulse sequence. We then designed a custom ultrasound-transparent cranial window implant for an adult patient undergoing reconstructive skull surgery after traumatic brain injury. We showed that fUSI could record brain activity in an awake human outside of the operating room. In a video game “connect the dots” task, we demonstrated mapping and decoding of task-modulated cortical activity in this individual. In a guitar-strumming task, we mapped additional task-specific cortical responses. Our proof-of-principle study shows that fUSI can be used as a high-resolution (200 μm) functional imaging modality for measuring adult human brain activity through an acoustically transparent cranial window.

Copyright and License

 © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Acknowledgement

We thank K. Pejsa for administrative assistance and participant planning. We thank M. Tanter at INSERM (Paris, France) for feedback and support throughout the research process. Last, we thank participant J for his willing participation.

Funding

This work was supported by NIH R01NS123663 (to R.A.A. and M.G.S.); the T&C Chen Brain-Machine Interface Center (to R.A.A. and M.G.S.); the Boswell Foundation (to R.A.A.), National Eye Institute NEI F30 EY032799 (to W.S.G.); a Josephine de Karman Fellowship (to W.S.G.); UCLA-Caltech Medical Scientist Training Program NIGMS T32 GM008042 (to W.S.G.); a Della Martin Postdoctoral Fellowship (to S.L.N.); Human Frontier Science Program Cross-Disciplinary Fellowship LT000217/2020-C (to C.R.); USC Neurorestoration Center (to C.L.); and the Howard Hughes Medical Institute (to M.G.S.).

Contributions

C.R., S.L.N., W.S.G., C.L., R.A.A., and M.G.S. conceptualized the study. C.R. and S.L.N. developed the fUSI sequence. S.L.N. designed the Doppler phantom. C.R. and S.L.N. conducted in vitro experiments, and C.R. performed rodent experiments, including surgeries and ultrasound data acquisitions. C.L. recruited study participants, and C.R., S.L.N., and W.S.G. recorded human fUSI data. C.L. and J.J.R. conducted craniectomy and cranioplasty surgeries. K.J. oversaw structural and functional MR imaging and analysis. W.S.G., S.L.N., and C.R. processed and analyzed ultrasound data. M.G.S., R.A.A., C.L., and V.C. supervised the research. C.R., W.S.G., S.L.N., M.G.S., and R.A.A. drafted the manuscript, which was reviewed and edited by C.R., W.S.G., S.L.N., M.G.S., R.A.A., C.L., and V.C.

Data Availability

All data associated with this study are available in the paper or the Supplementary Materials. The fUSI time series for the in vitro, rodent, and human data presented here are archived and freely available at CaltechDATA (https://doi.org/10.22002/f3y3k-em558). Code used to collect fUSI data, analyze fUSI time series, and generate the key figures and results is publicly available on GitHub at https://github.com/wsgriggs2/window-to-the-brain, and an archived version is stored on Zenodo at https://zenodo.org/doi/10.5281/zenodo.10645590 (53).

Conflict of Interest

C.R., W.S.G., S.L.N., R.A.A., C.L., and M.G.S. have filed a provisional patent application based on this research, filing no. CIT-9020-P entitled “A method for observing brain states using functional ultrasound imaging and a sonolucent material.” The other authors declare that they have no competing interests.

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Additional details

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May 30, 2024
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