A Wearable, Steerable, Transcranial Low‐Intensity Focused Ultrasound System
Christopher R. Bawiec, Peter J. Hollender, Sarah B. Ornellas, Jessica N. Schachtner, Jacob F. Dahill‐Fuchel, Soren D. Konecky, John J. B. Allen
Journal of Ultrasound in Medicine 2025, 44, 239-261 · 10.1002/jum.16600
Abstract
Objectives Transcranial low-intensity focused ultrasound (LIFU) offers unique opportunities for precisely neuromodulating small and/or deep targets within the human brain, which may be useful for treating psychiatric and neurological disorders. This article presents a novel ultrasound system that delivers focused ultrasound through the forehead to anterior brain targets and evaluates its safety and usability in a volunteer study. Methods The ultrasound system and workflow are described, including neuronavigation, LIFU planning, and ultrasound delivery components. Its capabilities are analyzed through simulations and experiments in water to establish its safe steering range. A cohort of 20 healthy volunteers received a LIFU protocol aimed at the anterior medial prefrontal cortex (amPFC), using imaging and questionnaires to screen for adverse effects. Additional development after the study also analyzes the effect of the skull and sinus cavities on delivered ultrasound energy. Results Simulations and hydrophone readings agreed with Conclusions The presented system safely delivered LIFU through the forehead while targeting the amPFC in all volunteers, and was well-tolerated. With the capabilities validated here and positive results of the study, this technology appears well-suited to explore LIFU's efficacy in clinical neuromodulation contexts.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to left amPFC (Phases 1.1-1.3, dose escalation)
Target: anterior prefrontal cortex — “left anterior medial Prefrontal Cortex (amPFC), (L) Brodmann Area 10”
Device: Openwater · Openwater · custom 400 kHz 2D matrix array (128 elements) with Verasonics Vantage driving electronics ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 400 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 5% | ⚑ |
| Sonication duration (s) | 30, 600swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 510, 650, 820swept | ✓? |
| In-situ Isppa (W/cm²) | 8.04, 13.1, 20.8swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.201, 0.327, 0.508swept | ✓✓✓ |
The ultrasound delivery parameters (frequency, pulse length, and pulse repetition frequency) remained the same throughout the study, but the pressure amplitude was systematically varied across three phases (PNP 510, 650, 820 kPa in Phases 1.1, 1.2, 1.3, respectively, with n=9, 6, 5 participants). In Phase 1.1 a single focus was used with a 30-second on-off pattern of pulse trains; in Phases 1.2 and 1.3 a multi-focus 'interleaved pulses' approach rastered across five foci was used with no on-off cycling. Total ultrasound delivery duration was 10 minutes per participant.
Flags from extraction
exposures[0].in_situ— Values are from k-Wave simulations assuming homogeneous soft tissue with the skull explicitly neglected ('beamforming was performed neglecting the presence of the skull'); classified as in_situ (at-target, simulated) rather than free_field because the simulation models the target location inside the head, not water. A separate post-hoc simulation using segmented skull data reported lower derated pressures (mean 0.34, 0.33, 0.45 MPa for the three target pressures) but is not captured in this field to avoid conflating two different simulation methods for the same exposure.exposures[0].timing.sonication_duration_s— The 10-minute figure is the total per-participant ultrasound delivery duration; internal on/off cycling in Phase 1.1 (30-s on-off pattern) versus continuous multi-focus delivery in Phases 1.2-1.3 means the length of a single uninterrupted train may differ from this total duration.exposures[0].timing.duty_cycle_pct— Not explicitly stated in the text for the actual study parameters; the configuration table lists a 'typical' pulse duration of 5 ms and PRI of 100 ms but duty cycle is not given directly.randomised— Participants were assigned sequentially to increasing-dose phases (first nine participants in Phase 1.1, then six in Phase 1.2, then five in Phase 1.3) in a conservative dose-escalation design, not a randomised allocation.