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A Noninvasive Focused Ultrasound-Evoked Electrophysiological Mapping Method With High Spatiotemporal Precision

Ye Yuan, Jie Zhao, Tian Liu, Jue Wang

IEEE Transactions on Biomedical Engineering 2026 · 10.1109/tbme.2025.3612200

rodenthealthyinvasive electrophysiologyhistology molecular

Abstract

Achieving noninvasive functional brain mapping with submillimeter spatial and millisecond temporal resolution remains a major technical challenge. Existing modalities fail to meet both requirements simultaneously: fMRI offers high spatial resolution but suffers from hemodynamic delays, while EEG provides superior temporal resolution yet lacks spatial specificity. We present a cortical mapping method that integrates focused ultrasound (FUS) stimulation with local field potential (LFP) recordings for high-resolution electrophysiological mapping. A 5 × 5 Cartesian scanning grid was applied over the barrel cortex. FUS pulses (4 MHz, 1.6 MPa peak negative pressure, 1Hz pulse repetition frequency) were sequentially delivered to each grid point, and peak LFP amplitudes were recorded at each site via a tungsten microelectrode to generate activation heatmap. Our method achieved approximately 0.45 mm spatial resolution and 10 ms temporal resolution in detecting FUS evoked LFP responses. The proposed FUS-LFP mapping paradigm enables high-resolution and time-precision visualization of cortical electrophysiological responses to noninvasive stimulation. This method provides a robust and scalable approach for probing evoked cortical responses and constructing functional brain maps, with promising translational relevance for preclinical neuroengineering.

Abstract via pubmed.

Speciesrat (Sprague-Dawley)
Subjects10 animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology, histology molecularLocal field potential (LFP) peak amplitude via tungsten microelectrode recording; cytochrome oxidase histological staining to anatomically validate the C2 barrel column
Direction of effectexcitatoryFUS pulses evoked local field potential responses in the C2 barrel column of primary somatosensory cortex that increased with acoustic pressure (mean amplitude rising from 16.2 uV at 0.8 MPa to 35.6 uV at 1.6 MPa; no detectable response at 0.4 MPa), and were spatially confined to the anatomically defined C2 barrel column (submillimeter resolution).
Adverse eventsnot reportedTheoretical estimations indicated a maximum temperature rise of approximately 0.1-0.2 degC, far below the 1 degC safety threshold; Ispta (83 mW/cm^2) was well below the FDA diagnostic ultrasound limit (720 mW/cm^2) and MI (0.8) was below the FDA limit (MI<1.9) and below MI values previously reported not to cause neuroinflammation.

Exposures

Exposure 1: FUS mapping of C2 barrel column, primary somatosensory cortex (exposed dura, craniotomy)

Target: primary somatosensory cortex — “C2 whisker barrel (bbl) column, left primary somatosensory cortex
Device: other named manufacturer · Siansonic, Inc. · HIFU

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)4,000✓✓
Pulse duration (ms)1✓✓
Pulse repetition frequency (Hz)1✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 0.1%
Sonication duration (s)not reported
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 estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Pressure, domain unspecified (kPa)400, 800, 1,200, 1,600swept?
Ispta, domain unspecified (W/cm²)0.083✓✓
Protocol, in the paper’s words

FUS was sequentially delivered to each of 25 spatial coordinates in a 5x5 scanning grid (0.2 mm step size) over the C2 barrel column, with 10 pulses per stimulation site; each site was stimulated twice and the response averaged. A preliminary multi-pressure experiment applied four pressure levels (0.4, 0.8, 1.2 and 1.6 MPa) in a randomized sequence at the same site, each repeated 10 times, before final parameters (1.6 MPa PNP, 1 ms pulse width, 1 Hz PRF, 10 pulses) were selected for the main mapping experiment.

Flags from extraction

  • exposures[0].unspecified_domain.pressure_kpaPressures (0.4-1.6 MPa PNP) are stated without specifying whether they are free-field (water-tank calibrated) or in-situ values; the transducer was aimed directly at the exposed dura through a craniotomy (no skull in the path), but the paper does not explicitly label the delivered PNP by domain, so it is recorded as unspecified_domain.
  • device.familyThe transducer manufacturer (Siansonic, Inc.) is a named commercial maker not covered by the specific vocabulary entries; classified as commercial_other.
  • exposures[0].timing.sonication_duration_sOnly pulse count (10 pulses per site) and PRF (1 Hz) are given; total sonication duration per site is not explicitly stated and was not computed.
  • randomisedRandomization refers to the order of the four pressure levels tested in the single-rat pilot experiment ('applied in a randomized sequence'), not group allocation across the 10-rat cohort.