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Effects of high‐intensity focused ultrasound on nerve conduction

Jessica L. Foley, James W. Little, Shahram Vaezy

Muscle & Nerve 2008 · 10.1002/mus.20932

rodenthealthyemg mephistology molecularbehaviour

Abstract

The effects of various exposures (intensity, duration) of high-intensity focused ultrasound (HIFU) on sciatic nerve conduction were investigated in vivo in rats. The objective was to identify HIFU exposures that produce biological effects ranging from partial to complete conduction block, indicating potential use of HIFU as an alternative to current clinical methods of inducing nerve conduction block. In the study, 26 nerves were exposed and treated with 5-s applications of 5.7-MHZ HIFU with acoustic intensities of 390, 2,255, 3,310, and 7,890 W/cm(2) (spatial peak, temporal peak). Compound muscle action potentials (CMAPs), in response to electrical stimulation of the nerve proximal to the HIFU site, were recorded from the plantar foot muscles immediately before and after HIFU treatment and 2 and 4 h after treatment. Furthermore, a preliminary long-term investigation was performed on 27 nerves with the same four sets of HIFU parameters. CMAPs were measured at the survival endpoint for each animal (7 or 28 days after treatment). For nerves treated with the three lower exposures, CMAPs decreased initially within 4 h or 7 days after HIFU treatment and then recovered to their baseline level at 28 days after treatment. For the highest exposure, however, CMAPs remained absent even 28 days after treatment. These exposure-dependent effects of HIFU on nerve function suggest its future potential as a novel treatment for severe spasticity and pain.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects13, 27swept animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsemg mep, histology molecular, behaviour — Compound muscle action potentials from plantar foot muscles; Masson's trichrome nerve histology; toe-spread and gait observation
Direction of effectinhibitoryCMAP amplitude fell with increasing intensity: transient decline recovering by 28 days at the three lower exposures, and no measurable CMAP at 7 or 28 days at 7,890 W/cm2.
Adverse eventsobservedAt the highest exposure nerves appeared necrosed with thickening and adhesions; histology showed axon swelling and myelin disruption, and haemorrhagic regions were seen at the two highest exposures.

Exposures

Exposure 1: 5.7 MHz HIFU, 5 s, four intensities, rat sciatic nerve

Target: sciatic nerve — “rat sciatic nerves”
Device: not reported

Pulse timing
Waveformnot reported
Fundamental frequency (kHz)5,700✓✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)5✓✓✓
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
Isppa, domain unspecified (W/cm²)390, 2,255, 3,310, 7,890swept✓✓✓⚑
Protocol, in the paper’s words

Single 5-s HIFU application per nerve with the focus placed at the centre of the exposed sciatic nerve via a titanium cone applicator; four intensities (390, 2,255, 3,310 and 7,890 W/cm2 spatial peak, temporal peak). Short-term (13 rats, recordings to 4 h) and long-term (27 rats, 7 or 28 days) studies used the same exposures.

Flags from extraction

  • n_subjects — Short-term study used 13 rats and long-term study 27 rats; the total is not stated, so group sizes are listed. Quote supports the first value; the long-term count is in the sentence 'Sprague-Dawley rats (n 27; 350-450 g) were used in this study.'
  • exposures[0].unspecified_domain.isppa_w_cm2 — Intensity given as spatial peak, temporal peak from hydrophone and force-balance measurements; medium not stated, so recorded as unspecified domain in the isppa field.
  • exposures[0].timing.waveform — Continuous versus pulsed operation not stated.
  • exposures[0].device.family — Transducer described as developed for visually guided HIFU (reference to an earlier paper); maker not named.
  • sham_type — Sham animals had the nerve exposed but no HIFU applied; contralateral untreated nerves also served as control. Coded as no_treatment_control as the closest term.
  • conditions — Paper is aimed at conduction block for spasticity and pain; highest exposure causes axon degeneration. Scope under condition D is borderline.