Brain injury during focused ultrasound neuromodulation for substance use disorder

Ali Rezai, Manish Ranjan, Aniruddha Bhagwat, Tasneem Arsiwala, Jeffrey Carpenter, Mark Schafer, Geoffrey Adams, Jennifer Marton, Padmashree Tirumalai, Daniel Farmer, James Mahoney, Victor Finomore

Brain Stimulation 2025, 18, 2050-2053 · 10.1016/j.brs.2025.10.012

human patientsubstance use disorderother mriclinical scaleautonomic physiology

Specieshuman

Subjects1 participants

Sessions per subject1

Randomisedyes

Blindingdouble

Sham / controlundescribed

Auditory controlnot reported

Readout timingboth

Anaesthesianot applicable

Readoutsother mri, clinical scale, autonomic physiology — Glasgow Coma Scale; CT; MR thermometry; acoustic feedback monitoring

Direction of effectnot assessedCase report of a safety event; direction of neuromodulation effect on brain activity was not the subject of this report.

Adverse eventsobservedImmediately after the second 90W/300s sonication the participant was found unarousable (GCS E1M5V1); MRI revealed petechial microhemorrhages within and beyond the targeted area, with subsequent hypercapnia, delayed recovery of consciousness, and residual memory/cognitive deficits at 5 months; the pattern was judged suggestive of inertial cavitation.

Exposures

Exposure 1: Bilateral NAc FUS neuromodulation (active treatment arm, adverse event case)

Target: nucleus accumbens — “bilateral nucleus accumbens (NAc)”
Device: Insightec · Insightec · Insightec 220kHz system (Exablate Neuro) ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	220	✓✓✓
Pulse duration (ms)	100	✓✓✓
Pulse repetition frequency (Hz)	0.333	✓✓✓⚑
Duty cycle (%)	3.3pulse duration × PRF gives 3.33%	✓✓✓
Sonication duration (s)	300	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	not reported
In-situ estimate	not reported
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported

Protocol, in the paper’s words

Each FUS treatment block consisted of bilateral NAc sonication lasting 300 seconds (up to 6 blocks), delivering therapeutic energy up to 100 W, with four individual sub-spots per NAc target treated sequentially at an effective pulse repetition time of 3 seconds. In the reported adverse event, an initial 90 W sonication was halted at 89 seconds by the acoustic feedback safety system; a second 90 W sonication then ran the full 300 seconds without a halt, after which the participant became unarousable.

Flags from extraction

exposures[0].free_field — Paper explicitly states pressure and intensity values are proprietary to the manufacturer and not disclosed: 'Technical information regarding pressure intensities and mechanical index are unique and proprietary to Insightec.'
sham_type — The mechanism of the sham condition is not described in this letter; recorded as 'other'.
exposures[0].timing.pulse_repetition_frequency_hz — PRF derived by converting the stated effective pulse repetition time (3 seconds) to Hz (1/3 = 0.333 Hz), consistent with the stated 3.3% duty cycle and 100 ms pulse duration.