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A Miniature Ultrasound Source for Neural Modulation

Samantha F. Schafer, Haley Croke, Andres Kriete, Hasan Ayaz, Peter A. Lewin, Catherine R. von Reyn, Mark E. Schafer

IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2023 · 10.1109/tuffc.2023.3322963

invertebratehealthybehaviour

Abstract

This work describes a unique ultrasound (US) exposure system designed to create very localized ( [Formula: see text]) sound fields at operating frequencies that are currently being used for preclinical US neuromodulation. This system can expose small clusters of neuronal tissue, such as cell cultures or intact brain structures in target animal models, opening up opportunities to examine possible mechanisms of action. We modified a dental descaler and drove it at a resonance frequency of 96 kHz, well above its nominal operating point of 28 kHz. A ceramic microtip from an ultrasonic wire bonder was attached to the end of the applicator, creating a 100- [Formula: see text] point source. The device was calibrated with a polyvinylidene difluoride (PVDF) membrane hydrophone, in a novel, air-backed, configuration. The experimental results were confirmed by simulation using a monopole model. The results show a consistent decaying sound field from the tip, well-suited to neural stimulation. The system was tested on an existing neurological model, Drosophila melanogaster, which has not previously been used for US neuromodulation experiments. The results show brain-directed US stimulation induces or suppresses motor actions, demonstrated through synchronized tracking of fly limb movements. These results provide the basis for ongoing and future studies of US interaction with neuronal tissue, both at the level of single neurons and intact organisms.

Abstract via europepmc.

Speciesfruit fly (Drosophila melanogaster)
Subjectsnot reported animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controldeafened subjects, control experiment
Readout timingonline
Anaesthesiaawake
Readoutsbehaviour — SLEAP deep-learning tracking of T2/T3 leg movements
Direction of effectbidirectionalUltrasound evoked leg movement in flies that were still and suppressed movement in flies that were already moving; responses were variable across trials.
Adverse eventsnone observedNo comprehensive histology; light microscopy of the brain surface before and after exposure showed no visual change; output calculated to preclude thermal or cavitation effects.

Exposures

Exposure 1: 96 kHz miniature microtip source over the Drosophila central brain

Target: drosophila neurons — “the center of the right hemisphere of the central brain”
Device: custom-built · modified dental ultrasonic descaler (Langevin stack) with 100 um ceramic wire-bonder microtip

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)96✓✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.5 ms (not stated by the paper)⚑
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)50✓✓✓⚑
Sonication duration (s)5✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)14✓✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot applicable
In-situ pressure (kPa)not applicable
In-situ Isppa (W/cm²)not applicable
In-situ Ispta (W/cm²)not applicable
Protocol, in the paper’s words

Tone bursts at 96 kHz, 1 kHz pulse repetition rate, duty cycle varied (30-80 %) with 50 % most consistent, delivered for 5 s inside a 15-s recording; 4-8 trials per fly with 8 min recovery. Bursts were always longer than 30 cycles because the source is resonant.

Flags from extraction

  • exposures[0].unspecified_domain.pressure_kpa — 'Estimated pressure level of 14 kPa' with no statement of domain; calibration used an air-backed hydrophone at 100 um from the tip and a monopole calculation gave 20 kPa.
  • exposures[0].timing.duty_cycle_pct — Duty cycle varied between 30-80 % (methods) or 20-80 % (discussion); 50 % is the proof-of-concept value recorded.
  • exposures[0].timing.pulse_duration_ms — Not stated.
  • n_subjects — Only 'representative examples from six flies' and 4-8 trials per fly are given; total not stated.
  • anaesthesia — Flies were cold-anaesthetised for preparation then head-fixed and behaving during sonication; recorded as awake.