A peer-reviewed letter published in Brain Stimulation, coauthored by several of the leading pioneers and foundational researchers in ultrasound neuromodulation, examines a reported serious adverse event following focused ultrasound neuromodulation at 220 kHz. The authors argue that safety cannot be determined from intensity or mechanical index alone. Lower-frequency ultrasound—approximately 200–340 kHz—has lower cavitation thresholds, broader focal volumes, and greater susceptibility to standing waves, which can narrow mechanical and spatial safety margins, particularly when high-output systems developed for other applications are repurposed for neuromodulation.
By contrast, carefully controlled mid-frequency tFUS around 500–700 kHz has shown a strong safety record. For instance, in a study with the 650-kHz BrainSonix BX Pulsar 1002 device, the right-amygdala was sonicated up to MI=2.803 and ISPTA.3 10.08 W/cm² produced no adverse events or MRI-detectable injury.
The authors caution that these findings are not a direct comparison with the reported 220-kHz injury. Their conclusion is that frequency, device architecture, focal geometry, dosing, and patient-specific factors must all be considered when evaluating risk. Purpose-built neuromodulation systems, careful parameter selection, and transparent reporting of acoustic exposures are essential for advancing tFUS safely.
