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Design, Development, and Operation of a Low-Intensity Focused Ultrasound Pulsation (LIFUP) System for Clinical Use

Mark E. Schafer, Norman M. Spivak, Alexander S. Korb, Alexander Bystritsky

IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2021, 68, 54-64 · 10.1109/tuffc.2020.3006781

human healthyhealthyother mri

Abstract

Noninvasive low-intensity focused ultrasound pulsation (LIFUP) neuromodulation provides a unique approach to both investigating and treating the brain. This work describes a well-calibrated, simple-to-use ultrasound stimulation system for neuromodulation studies. It provides a single-element 650-kHz transducer design and a straightforward control mechanism, with extensive calibration and internal electronic monitoring to prevent unwanted over or under treatment. One goal of this approach is to relieve researchers of many of the details associated with developing their own exposure equipment. A unique transducer positioning system and distinctive MRI fiducial targets simplify alignment and targeting. The system design, control software, calibration, and alignment techniques are described in detail. Examples of transducer targeting and neurostimulation using the system are provided.

Abstract via europepmc.

Specieshuman
Subjects1 participants
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsother mriPulsed Arterial Spin Labeling (ASL) perfusion imaging (3-D turbo GRASE, FAIR QII), before/after subtraction
Direction of effectexcitatoryLIFUP sonication produced an increase in cerebral blood flow (measured with ASL) localized to the entorhinal cortex focal region in a single participant.
Adverse eventsnot reported

Exposures

Exposure 1: fMRI/ASL example, entorhinal cortex, single participant (65-mm focal-depth transducer)

Target: entorhinal cortex — “entorhinal cortex
Device: BrainSonix · Brainsonix, Inc. · BX1002 (Stimulator)

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.5 ms (not stated by the paper)
Pulse repetition frequency (Hz)100✓✓
Duty cycle (%)5✓✓
Sonication duration (s)30✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)710✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)0.942✓✓
In-situ estimatederatingsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)0.72✓✓
Protocol, in the paper’s words

The ultrasound transmit parameters were 942 mW/cm2 ISPTA.0 (720 mW/cm2 ISPTA.3), 100-Hz PRF, 5% duty cycle, 0.71 MPa pr.0, and 30 s ON/30 s OFF for one 10-min treatment block, targeted using MRI fiducial-guided alignment with a 65-mm focal-depth transducer.

Flags from extraction

  • exposures[0].timing.pulse_duration_msPRF (100 Hz) and duty cycle (5%) are stated but pulse duration is never stated directly; not computed to avoid unauthorised arithmetic.
  • exposures[0].target.termsPaper does not explicitly name an intended target region beyond 'temporal region'; entorhinal cortex is inferred from the text stating the observed perfusion change was 'in the focal region'.
  • exposures[0].in_situ.ispta_w_cm2720 mW/cm2 is the FDA-style derated (0.3 dB/cm/MHz) value the system displays alongside the nonderated value, not a measured or simulated in-brain value; classified as in_situ via 'derating' method per the paper's own description of this approach.

Notes: This is primarily a device/engineering description paper (LIFUP/BX1002 system). Only one concrete exposure with reported parameters is presented as the paper's own data (Section V, single-participant fMRI/ASL example). Other clinical results (2015 epilepsy case series, 2016 disorders-of-consciousness case) are cited from separate prior publications and were not re-extracted as exposures here.