ORCID

Abstract

Transcranial ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation. The International Transcranial Ultrasonic Stimulation Safety and Standards consortium (ITRUSST) has established consensus on considerations for nonsignificant biophysical risk of TUS, drawing upon the literature and established regulations for biomedical devices. Here, we assume the application of TUS to individuals without contraindications, compromised thermoregulation, vascular vulnerabilities, or administered ultrasound contrast agents. In this context, we present a concise yet comprehensive set of levels for nonsignificant risks of TUS application. For mechanical effects, it is non-significant risk if the mechanical index (MI) or the mechanical index for transcranial application (MItc) does not exceed 1.9. For thermal effects, it is non-significant risk if any of the following three levels are met: the peak temperature rise does not exceed 2 °C or the peak absolute temperature does not exceed 39 °C, assuming a baseline temperature of 37 °C, the thermal dose does not exceed 2 CEM43 in brain tissue, 16 CEM43 in bone tissue, and 21 CEM43 in skin tissue, or specific values of the thermal index (TI) for a given exposure time. This report reflects a consensus expert opinion and can inform, but not replace, regulatory guidelines or official international standards. Similarly, this consensus can inform, but not replace, ethical evaluation, which weighs the total burden, risks, and benefits of the proposed action. The stated levels are not safety limits per se, and further data is needed to establish the threshold for significant risk. We review literature relevant to our considerations and discuss limitations and future developments of our approach.

Publication Date

2025-11-01

Publication Title

Brain Stimulation

Volume

18

Issue

6

ISSN

1935-861X

Acceptance Date

2025-10-06

Deposit Date

2025-12-02

Funding

JFA is supported by the Agence Nationale de la Recherche (ANR-20- CE19-0013 and ANR-10-EQPX-15), by the Technological Research Accelerator program of INSERM, and by the Focused Ultrasound Foundation (Center of Excellence program). JFA and DA are supported by the Bettencourt Schueller Foundation. EF is supported by a UKRI Medical Research Council Future Leaders Fellowship grant (MR/T023007/1), a BBSRC grant (BB/Y001494/1), and the Advanced Research + Invention Agency (ARIA). CFC is supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (UG3NS135551). EJB is supported by CURE Epilepsy and the Epilepsy Foundation New England. JS is supported by the Agence Nationale de la Recherche (ANR-2-CE37-0021). CRB is supported by the National Institute for Health and Care Research. CJS holds a Senior Research Fellowship, funded by the Wellcome Trust (224430/Z/21/Z). MKF is supported by Wellcome Trust grant 223263/Z/21/Z and UKRI grant EP/ X021815/1. SSY was partially supported by Fund to Sustain Research Excellence from Brigham Research Institute. CKH is supported by a Lantheus™ research contract and holds the Hanna Endowed Chair of Cardiology at the University of Cincinnati. EM is supported by a UKRI Future Leaders Fellowship (MR/T019166/1), and by the EIC Pathfinder project CITRUS (Grant Agreement No. 101071008) funded by the EU Horizon Europe research and innovation program. LV is supported by a VIDI fellowship funded by the Dutch Research Council (NWO, 18919) and is a co-applicant on an EIC Pathfinder project funded by the European Innovation Council (EIC, 101071008) and on an ERC Advanced project funded by the European Research Council (ERC, MediCoDe). KBP is supported by grants from the National Institutes of Health (NIH R01 MH131684, NIH R01 NS112152, NIH R01 EB032743).

Keywords

Biophysical effects, Neuromodulation, Non-invasive brain stimulation, Regulations, Safety, Standards, Transcranial ultrasound stimulation

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

First Page

1896

Last Page

1905

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