Brain-wide hemodynamic responses to precise transcranial ultrasound neuromodulation
Héctor Estrada, Chuan Liu, Ali Özbek, Zhenyue Chen, Michael Reiss, Shy Shoham, Daniel Razansky
Brain Stimulation 2026 · 10.1016/j.brs.2025.11.005
Abstract
Background Despite the high potential of transcranial ultrasound stimulation (TUS) for non-invasive brain therapy and interrogation, real-time monitoring of brain responses to TUS remains a challenge. Traditional methods to monitor direct neural responses are invasive and mostly incompatible with precise TUS delivery while other non-invasive approaches to visualize the induced responses suffer from poor penetration depth, lack of sensitivity, or low temporal resolution. Objective We present an integrated approach for high precision delivery of ultrasound into the mouse brain and simultaneous whole-brain oximetry with functional optoacoustic tomography to characterize the hemodynamic response elicited by TUS. Methods A spherically focused ultrasound array was employed to non-invasively deliver holographic TUS and simultaneously detect multispectral optoacoustic signals from the brains of anesthetized mice. Ultrasound pressure and pulse duration were varied, while the number of stimuli (5), stimulation duration (15 s), and ultrasound frequency (3 MHz) were kept constant. The acquired optoacoustic data were tomographically reconstructed and spectrally unmixed to render three-dimensional maps of oxygenated and deoxygenated hemoglobin in real time. Results TUS-evoked brain-wide hemodynamics were efficiently monitored via spectroscopic optoacoustic imaging with high spatial and temporal resolution. Holographic TUS targeted to the somatosensory cortex elicited distinct hemodynamic responses, which extended beyond the stimulated region, involving subcortical arteries and pial veins. Conclusions Our method provides new transformative non-invasive capabilities to study the effects of ultrasound on a living brain thus help unleash the strong potential of TUS in neuroscience and medicine.
Abstract via europepmc.
Exposures
Exposure 1: Holographic TUS to somatosensory cortex
Target: primary somatosensory cortex — “primary somatosensory cortex”
Device: IGT / Imasonic · Imasonic, France · 512-channel spherically focused matrix array (POTUS) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | 50, 100swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 4, 8swept | ✓✓✓⚑ |
| Duty cycle (%) | 40 | ✓✓✓ |
| Sonication duration (s) | 15.2 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 900, 1,200swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 27, 48swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | 11, 19swept | ✓✓✓ |
During the 15.2 s of the TUS stimulation, 100 ms US pulses at 3 MHz are repeated at 4 Hz (40% duty cycle); pulse duration was also reduced to 50 ms. Five stimulations spaced by 40 s were delivered.
Flags from extraction
exposures[0].in_situ.pressure_kpa— Peak pressures 1.2 and 0.9 MPa (Isppa 48 and 27 W/cm2) are derated from free-field using a 6 dB skull insertion loss; the paper's 'peak pressure' is not stated as free-field separately.exposures[0].unspecified_domain.ispta_w_cm2— Ispta (19 and 11 W/cm2) is given in a figure legend without a domain.exposures[0].timing.pulse_repetition_frequency_hz— Methods give 4 Hz for 100 ms pulses; the discussion gives 4-8 Hz, so 8 Hz presumably applies to 50 ms pulses at the same duty cycle (not stated directly).exposures[0].timing.sonication_duration_s— Abstract says 15 s; methods say 15.2 s.auditory_control— No auditory control during the experiment; the discussion argues from prior work and from absence of auditory cortex hemodynamic signal, and says controls are future work.exposures[0].device.family— Custom 512-element array from Imasonic; driven by Falkenstein Mikrosysteme electronics.