  Transcranial ultrasonic stimulation (TUS) is an emerging technology for
non-invasive brain stimulation. In a series of meetings, the International
Consortium for Transcranial Ultrasonic Stimulation Safety and Standards
(ITRUSST) has established expert consensus on considerations for the
biophysical safety of TUS, drawing upon the relevant diagnostic ultrasound
literature and regulations. This report reflects a consensus expert opinion and
can inform but not replace regulatory guidelines or official international
standards. Their establishment by international and national commissions will
follow expert consensus. Similarly, this consensus will inform but not replace
ethical evaluation, which will consider aspects beyond biophysical safety
relevant to burden, risk, and benefit, such as physiological effects and
disease-specific interactions. Here, we assume the application of TUS to
persons who are not at risk for thermal or mechanical damage, and without
ultrasound contrast agents. In this context, we present a concise yet
comprehensive set of levels for a nonsignificant risk of TUS application. For
mechanical effects, it is safe if the mechanical index (MI) or the mechanical
index for transcranial application (MItc) does not exceed 1.9. For thermal
effects, it is safe if any of the following three levels are met: a temperature
rise less than 2 C, a thermal dose less than 0.25 CEM43, or specific values of
the thermal index (TI) for a given exposure time. We review literature relevant
to our considerations and discuss limitations and future developments of our
approach.
