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Integrated neuronavigation and acoustic-thermal modeling for simultaneous transcranial ultrasound stimulation (TUS) and functional MRI

Moon Jeong, Ali K Zadeh, Alan Coreas, Fady Girgis, Samuel Pichardo, G Bruce Pike

Journal of Neural Engineering 2026 · 10.1088/1741-2552/ae9347

human healthyhealthyfmriother mriclinical scale

Abstract

Objective . We present and validate an integrated workflow for accurate and stable targeting of a TUS transducer inside the MRI scanner using subject-specific imaging, neuronavigation, acoustic-thermal modeling, transducer positioning and fixation, and in-scanner verification. Approach . A stimulation target was defined in the left primary motor cortex (M1) hand knob using structural imaging and task-based functional magnetic resonance imaging (fMRI) collected during a planning session, then transferred to neuronavigation for trajectory planning and scalp marking. Acoustic and thermal simulations characterized the acoustic beam geometry and adjusted ultrasound power to achieve the desired acoustic field at the target within safety constraints. During the experiment scanning session, low-resolution T 1 -weighted localizer images visualized transducer fiducials and the planned target directly on the scanner console, enabling iterative in-bore refinement. Main results . Coupled with a custom MRI-compatible transducer fixation cap enabling controlled multi-axis adjustments, this workflow achieved a mean post-refinement off-target distance of 1.41.0 mm across five participants over 19 sessions, falling within one fMRI voxel (2.5 mm) of the planned target in 17 of 19 sessions (89%). Repeat transducer position verification approximately 40 min after initial setup showed minimal positional drift (0.2 mm). In an expanded cohort of 12 participants with balanced sex distribution (six males, six females), mean post-adjustment off-target distance was 2.180.78 mm in males and 1.930.69 mm in females, with comparable performance between sexes (Mann-Whitney U = 22; descriptive), and an overall success rate of nine of 12 sessions (75%). fMRI tSNR in M1 was preserved with the passive transducer (left-to-right M1 ratio 0.900.12) and during active sonication (0.900.09) across the same 12 participants, indicating that the 20 mm coupling gel pad effectively mitigated susceptibility-related signal dropout and that active sonication introduced no additional signal degradation. Significance . This workflow provides a practical experimental foundation for in-scanner targeting and verification for simultaneous human TUS-fMRI studies, with MRI signal quality preserved during active sonication and consistent targeting performance across male and female participants.

Abstract via europepmc.

Specieshuman
Subjects12 participants
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutsfmri, other mri, clinical scale — fMRI tSNR in left/right M1 during passive and active sonication; targeting off-target distance on T1w; post-session symptom questionnaire
Direction of effectnot assessedMethods and workflow paper; the authors state it does not present TUS stimulation results or evaluate neuromodulatory effects. The outcome was MRI signal quality (tSNR) and targeting accuracy.
Adverse eventsnone observedNo participants reported adverse events and no sessions were terminated; post-session symptom questionnaire administered to 16 cap participants (headache 4/16 most common); simulations constrained to MI < 1.9 and temperature rise < 2 C.

Exposures

Exposure 1: Left M1 hand knob, BabelBrain-planned in-scanner TUS

Target: primary motor cortex — “hand knob region of the left primary motor cortex”
Device: BrainSonix · BrainSonix Inc. · BX Pulsar 1002 ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓✓
Pulse duration (ms)1✓✓✓
Pulse repetition frequency (Hz)100✓✓✓
Duty cycle (%)10pulse duration × PRF gives 10%✓✓✓
Sonication duration (s)90✓✓✓⚑
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 estimatesimulationmean or range across subjects
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)1.73, 4.08swept✓✓✓⚑
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Sonication parameters applied across all participants: fundamental frequency 650 kHz, PD 1 ms, PRF 100 Hz, DC 10%, pulse train duration 90 s, 2 sonication repetitions (concurrent TUS-fMRI).

Flags from extraction

  • n_subjects — 17 unique participants overall, but active sonication (tSNR analysis) stated for 12 participants (Subjects 6-17); the others only had positioning validation. Recorded 12.
  • exposures[0].in_situ.isppa_w_cm2 — Simulated Isppa after skull attenuation across participants (mean 3.50 +/- 0.87 W/cm2; range given); per-subject values only in supplementary table S3. No free-field values stated in the main text.
  • exposures[0].timing.sonication_duration_s — Pulse train duration stated for simulation and for the concurrent TUS-fMRI acquisition; study is a methods paper with no stimulation outcomes.