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Transcranial functional ultrasound imaging shows widespread hemodynamic changes induced by focused ultrasound (FUS)

Jonas Bendig, Christian Aurup, Samuel G. Blackman, Erica P. McCune, Seongyeon Kim, Elisa E. Konofagou

Scientific Reports 2026 · 10.1038/s41598-026-62583-3

rodenthealthycerebral haemodynamicshistology molecular
Speciesmouse (C57BL/6)
Subjects22, 5swept animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer, sound only
Auditory controlsound only sham
Readout timingboth
Anaesthesiaanaesthetised
Readoutscerebral haemodynamics, histology moleculartranscranial functional ultrasound imaging (fUSI) / power Doppler imaging of cerebral blood volume (CBV); H&E histology for safety assessment; thermocouple temperature measurement
Direction of effectmixed or unclearTranscranial FUS produced widespread, mostly cortical, positive (increased) CBV responses that scaled with pressure; cranial-window FUS produced both positive and, at higher frequency, significant negative CBV correlations, and the authors attribute much of the transcranial response to skull-mediated thermal effects rather than direct neuromodulation.
Adverse eventsnone observedWe found no signs of structural changes or blood cell extravasations in H&E staining in n = 2 mice that were sacrificed 24 h following FUS with the highest pressure used for transcranial FUS (center frequency = 1.68 MHz, PNP = 2.6 MPa, Supplementary Figure 5 c/d).

Exposures

Exposure 1: Transcranial FUS, 1.68 MHz (H-204)

Target: primary somatosensory cortex, hippocampus, thalamus — “transcranial/cranial-window sonication along midline or ±1 mm ML; sonicated structures (somatosensory cortex, hippocampus, thalamus) depended on the AP imaging plane
Device: Sonic Concepts · Sonic Concepts Inc, Bothell, WA, USA (transducer); Vermon S.A., Tours, France (imaging array); Verasonics Inc. (Vantage 256 system) · H-204 / H-215 single-element annular transducer with L22-14vXLF imaging array

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,680✓✓
Pulse duration (ms)150✓✓
Pulse repetition frequency (Hz)1✓✓
Duty cycle (%)64pulse duration × PRF gives 15%, which disagrees with the stated value✓✓
Sonication duration (s)20✓✓
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 estimatederatingmean or range across subjects
In-situ pressure (kPa)800, 2,600swept✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)1.9, 20.06swept✓✓
Protocol, in the paper’s words

A block design was implemented consisting of a 60 s baseline imaging block followed by four 20 s FUS blocks with intervals randomized between 60 and 90 s. Each 20-s FUS block consisted of a 150-ms burst delivered at ~1 Hz (H-204) or ~2 Hz (H-215) ("sonication frequency"), amplitude-modulated by a 1-kHz half-sine envelope corresponding to an energy-equivalent duty cycle of 64%; this nested burst/AM structure does not reduce to a single PRF-duty-cycle pair.

Exposure 2: Cranial-window FUS, 1.68 MHz (H-204, non-derated)

Target: primary somatosensory cortex, hippocampus, thalamus — “transcranial/cranial-window sonication along midline or ±1 mm ML; sonicated structures (somatosensory cortex, hippocampus, thalamus) depended on the AP imaging plane
Device: Sonic Concepts · Sonic Concepts Inc, Bothell, WA, USA (transducer); Vermon S.A., Tours, France (imaging array); Verasonics Inc. (Vantage 256 system) · H-204 / H-215 single-element annular transducer with L22-14vXLF imaging array

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,680✓✓
Pulse duration (ms)150✓✓
Pulse repetition frequency (Hz)1✓✓
Duty cycle (%)64pulse duration × PRF gives 15%, which disagrees with the stated value✓✓
Sonication duration (s)20✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)700, 2,800swept✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)1.45, 23.27swept✓✓
In-situ estimatemeasurementmean or range across subjects
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

A block design was implemented consisting of a 60 s baseline imaging block followed by four 20 s FUS blocks with intervals randomized between 60 and 90 s. Each 20-s FUS block consisted of a 150-ms burst delivered at ~1 Hz (H-204) or ~2 Hz (H-215) ("sonication frequency"), amplitude-modulated by a 1-kHz half-sine envelope corresponding to an energy-equivalent duty cycle of 64%; this nested burst/AM structure does not reduce to a single PRF-duty-cycle pair.

Exposure 3: Cranial-window FUS, 4 MHz (H-215, derated brain tissue)

Target: primary somatosensory cortex, hippocampus, thalamus — “transcranial/cranial-window sonication along midline or ±1 mm ML; sonicated structures (somatosensory cortex, hippocampus, thalamus) depended on the AP imaging plane
Device: Sonic Concepts · Sonic Concepts Inc, Bothell, WA, USA (transducer); Vermon S.A., Tours, France (imaging array); Verasonics Inc. (Vantage 256 system) · H-204 / H-215 single-element annular transducer with L22-14vXLF imaging array

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)4,000✓✓
Pulse duration (ms)150✓✓
Pulse repetition frequency (Hz)2✓✓
Duty cycle (%)64pulse duration × PRF gives 30%, which disagrees with the stated value✓✓
Sonication duration (s)20✓✓
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 estimatederatingmean or range across subjects
In-situ pressure (kPa)960, 2,230swept✓✓
In-situ Isppa (W/cm²)31.18, 168.2swept✓✓
In-situ Ispta (W/cm²)2.99, 16.15swept✓✓
Protocol, in the paper’s words

A block design was implemented consisting of a 60 s baseline imaging block followed by four 20 s FUS blocks with intervals randomized between 60 and 90 s. Each 20-s FUS block consisted of a 150-ms burst delivered at ~1 Hz (H-204) or ~2 Hz (H-215) ("sonication frequency"), amplitude-modulated by a 1-kHz half-sine envelope corresponding to an energy-equivalent duty cycle of 64%; this nested burst/AM structure does not reduce to a single PRF-duty-cycle pair.

Flags from extraction

  • n_subjectsPaper gives separate mouse counts for transcranial (n=22) and cranial-window (n=5) cohorts; unclear whether the cranial-window subgroup overlaps with the transcranial cohort (different age ranges given), so totals are not summed.
  • exposures[0].in_situ.isppa_w_cm2The Isppa row in Table 1 is garbled in the source text/table conversion (a numeric range appears with no clear skull/transcranial vs cranial-window label attached); left not_reported rather than guessing the attribution.
  • exposures[1].in_situ.isppa_w_cm2Same Table 1 formatting/garbling issue as above; the non-derated cranial-window H204 Isppa value could not be unambiguously identified.
  • exposures[2].in_situ.ispta_w_cm2Table 1 lists the Ispta label for 'Derated: brain tissue, Cranial window, H215' but the corresponding numeric value appears to be missing/garbled in the source table.
  • exposures[0].timing.duty_cycle_pctThe paper states an energy-equivalent duty cycle of 64% arising from a 1-kHz amplitude-modulated sine envelope within each 150-ms burst; this differs conceptually from the classic PRF x pulse-duration duty cycle and does not arithmetically reconcile with the ~1 Hz (H-204) / ~2 Hz (H-215) burst repetition rate mentioned elsewhere -- recorded as stated but flagged as an unusual/nested definition.
  • exposures[0].target.termsFUS focal position and imaging plane varied across animals (AP -0.2 to -2.0 mm from Bregma); the exact sonicated structure was not fixed and multiple candidate regions (somatosensory cortex, hippocampus, thalamus) are named as possibilities depending on plane.
  • exposures[1].device.familyNo single named commercial neuromodulation device family fits; classified as commercial_other reflecting the combination of a Sonic Concepts transducer with a Vermon imaging array driven by a Verasonics research system.