A Wearable, Steerable, Transcranial Low-Intensity Focused Ultrasound System.

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. 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. Simulations and hydrophone readings agreed with <5% error, and the safe steering range was found to encompass a 1.8 cm × 2.5 cm × 2 cm volume centered at a depth 5 cm from the surface of the skin. There were no adverse effects evident on qualitative assessments, nor any signs of damage in susceptibility-weighted imaging scans. All participants tolerated the treatment well. The interface effectively enabled the users to complete the workflow with all participants. In particular, the amPFC of every participant was within the steering limits of the system. A post hoc analysis showed that "virtual fitting" could aid in steering the beams around subjects' sinuses. 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.

Introduction

Purpose Transcranial ultrasound stimulation

Study Objective To present and evaluate the safety and usability of a novel transcranial low-intensity focused ultrasound system for targeting the anterior medial prefrontal cortex through the forehead in healthy volunteers.

Animal model / Human subject Human (Homo sapiens), strain: N/A, age: None, sex: None; n=20 healthy volunteers

Disease model Healthy

MRI or image guidance method Neuronavigation (Localite stereotactic neuronavigation): stereo‑camera tracking of retroreflective fiducials on headset and transducer with co‑registration to each participant's MRI/MNI coordinates

Targeted brain region(s) Anterior Medial Prefrontal Cortex (Ampfc)

Outcomes and Safety

Summary of Outcomes Transcranial low‑intensity focused ultrasound (LIFU) to the anterior medial prefrontal cortex (amPFC) in 20 healthy volunteers was well tolerated with no adverse events or SWI imaging signs of damage and achieved a thermally‑safe steerable volume of ~1.8×2.5×2 cm centered ~5 cm deep. Three parameter sets were tested and successfully delivered within safety limits: Phase 1.1 (PNP 510 kPa; ISPPA 8.04 W/cm2; ISPTA 201 mW/cm2; MI 0.806; TIC ~0.325), Phase 1.2 (PNP 650 kPa; ISPPA 13.1 W/cm2; ISPTA 327 mW/cm2; MI 1.03; TIC ~0.536), and Phase 1.3 (PNP 820 kPa; ISPPA 20.8 W/cm2; ISPTA 508 mW/cm2; MI 1.3; TIC ~1.48).

Safety-related matter The study reported no adverse effects or imaging findings—no reported AEs and no signs of damage on susceptibility-weighted imaging—and all 20 participants tolerated the LIFU sessions well.

Brain Region

Ultrasound Parameters

Ultrasound instrument Verasonics Vantage Ultrasound Acquisition platform (Verasonics Inc, Kirkland, WA); custom 400 kHz 2D matrix array transducer (128 elements, 11×12, square elements with 4.1 mm pitch, surface area ~21.5 cm²), cylindrically focused with 50 mm radius of curvature; focal spot @50 mm: 4.5 mm diameter (−3 dB).

FUS Frequency 400 kHz

FUS Pressure 0.82 MPa (typical); 0.10 MPa (min); 1.00 MPa (max)

FUS Mode pulsed

Pulse duration 5 ms

Duration of a single FUS session 10 minutes

Focal Characteristics Focal depth: 5 cm (50 mm). Focal length: 50 mm (radius of curvature). Aperture size: ~21.5 cm^2 (array surface area; element pitch 4.1 mm).

Treatment frequency Single

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