Vagus nerve modulation using focused pulsed ultrasound: Potential applications and preliminary observations in a rat

Eduardo J. Juan, Rafael González, Gabriel Albors, Matthew P. Ward, Pedro Irazoqui

International Journal of Imaging Systems and Technology 2014, 24, 67-71 · 10.1002/ima.22080

rodenthealthyinvasive electrophysiology

Abstract

The use of focused ultrasonic waves to modulate neural structures has gained recent interest due to its potential in treating neurological disorders non-invasively. While several papers have focused on the use of ultrasound neuromodulation on peripheral nerves, none of these studies have been performed on the vagus nerve. We present preliminary observations on the effects of focused pulsed ultrasound (FPUS) on the conduction of the left cervical vagus nerve of a Long Evans rat. Ultrasound energy was applied at a frequency of 1.1 MHz, and at spatial-peak, temporal average intensities that ranged from 13.6 to 93.4 W/cm 2 . Vagus nerve inhibition was observed in most cases. Results of this preliminary study suggested that there is a proportional relationship between acoustic intensity and the level of nerve inhibition.

Abstract via europepmc.

Speciesrat (Long-Evans)

Subjects1 animals

Sessions per subject1

Randomisednot reported

Blindingnot reported

Sham / controlnone

Auditory controlnot reported

Readout timingboth

Anaesthesiaanaesthetised

Readoutsinvasive electrophysiology — Compound action potentials (CAP) recorded from the vagus nerve via cuff electrodes, following supramaximal electrical stimulation

Direction of effectinhibitoryVagus nerve compound action potential amplitude decreased and latency increased during ultrasound exposure in most trials, with a proportional relationship between acoustic intensity (Ispta) and the degree of inhibition.

Adverse eventsnot reportedAcoustic gel temperature increases after 15 s of ultrasound exposure were measured for each parameter combination (Table I), ranging up to a mean of about 0.93 degrees C; no explicit assessment of tissue damage or adverse events in the nerve was reported.

Exposures

Exposure 1: Left cervical vagus nerve, focused pulsed ultrasound at varying intensity/PRF/duty cycle

Target: vagus nerve — “left cervical vagus nerve”
Device: Sonic Concepts · Sonic Concepts, Washington · H-101 ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	1,100	✓✓✓
Pulse duration (ms)	not reported	⚑
Pulse repetition frequency (Hz)	1,000, 1,000, 1,000, 330, 330, 330, 200, 200, 200swept	✓✓✓
Duty cycle (%)	90.9, 90.9, 90.9, 30.3, 30.3, 30.3, 18.2, 18.2, 18.2swept	✓✓✓
Sonication duration (s)	15	✓✓✓

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 estimate	not 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)	74.8, 89, 102.8, 74.8, 89, 102.8, 74.8, 89, 102.8swept	✓✓✓⚑
Ispta, domain unspecified (W/cm²)	68, 80.9, 93.4, 22.7, 27, 31.1, 13.6, 16.2, 18.7swept	✓?

Protocol, in the paper’s words

A total of nine trials were performed on a single rat, each combining one of three intensity levels with one of three PRF/duty-cycle settings (Table I). Each trial consisted of 5 s of initial recording of evoked potentials without ultrasound, 15 s with ultrasound exposure, and 10 s of recovery.

Flags from extraction

exposures[0].unspecified_domain.isppa_w_cm2 — Paper never states whether the reported intensities are free-field (water) or in-situ values delivered to the surgically exposed nerve; placed in unspecified_domain.
exposures[0].timing.pulse_duration_ms — PRF and duty cycle are both given per trial, which would let pulse duration be computed, but the paper does not state a pulse duration directly, so it is left not_reported per the no-arithmetic rule.