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  • Perspective
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Imaging the brain by traversing the skull with light and sound

Nature Biomedical Engineering (2025)Cite this article

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Abstract

Optical and ultrasonic techniques for imaging the living brain have traditionally been limited to low-resolution interrogations or highly invasive craniotomy procedures. Localization-based techniques for super-resolution ultrasound and optical imaging, as well as hybrid optoacoustic techniques, are now enabling multiscale interrogations of the brain to exploit anatomical, functional and molecular contrasts non-invasively or minimally invasively. However, the skull bone remains a substantial obstacle to the transcranial application of light- and sound-based imaging techniques. Our knowledge of the skull’s acoustic properties inherited from transcranial ultrasound has been primarily limited to a narrowband and normal-incidence-angle detection regimen, which is inapplicable to more advanced ultrasound and optoacoustic brain imaging technology. In this Perspective, we examine the transcranial wave-propagation problem, as well as recent efforts to characterize and model skull-induced distortions and develop compensatory strategies. We then summarize recent preclinical and human applications of brain imaging and delve into the most pressing challenges facing this dynamic field at the crossroads of physics, engineering and medicine.

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Fig. 1: Anatomy of the skulls of small animals and humans, as well as physical phenomena involved in the transcranial propagation of light and ultrasound.
Fig. 2: Experimental characterization and modelling of the transcranial propagation of light and ultrasound.
Fig. 3: Transcranial brain imaging in rodent models.
Fig. 4: Imaging the human brain with light and sound.
Fig. 5: Transcranial localization angiography techniques.
Fig. 6: Skull-corrected transcranial imaging.

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Acknowledgements

We acknowledge support from the Swiss National Science Foundation (grant 310030_192757), Innosuisse—the Swiss Innovation Agency (grant 51767.1 IP-LS), the Personalized Health and Related Technologies grant of the ETH Domain (PHRT-582) and the US National Institutes of Health (grant RF1-NS126102).

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Authors and Affiliations

  1. Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, Zurich, Switzerland

    Héctor Estrada & Daniel Razansky

  2. Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, Zurich, Switzerland

    Héctor Estrada & Daniel Razansky

  3. Physics for Medicine Paris, Inserm, ESPCI Paris, PSL Research University and Centre National de la Recherche Scientifique, Paris, France

    Thomas Deffieux, Justine Robin & Mickaël Tanter

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  1. Héctor Estrada
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  2. Thomas Deffieux
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  5. Daniel Razansky
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H.E. and D.R. initiated and coordinated the project. D.R. and M.T. conceptualized the manuscript. H.E. designed the figures. All authors performed the literature research, wrote and edited the manuscript.

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Correspondence to Mickaël Tanter or Daniel Razansky.

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Estrada, H., Deffieux, T., Robin, J. et al. Imaging the brain by traversing the skull with light and sound. Nat. Biomed. Eng (2025). https://doi.org/10.1038/s41551-025-01433-5

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