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Low-Intensity Pulsed Ultrasound Neuromodulation of a Rodent's Spinal Cord Suppresses Motor Evoked Potentials

Yohannes Tsehay, Yinuo Zeng, Carly Weber-Levine, Tolulope Awosika, Max Kerensky, Andrew M. Hersh, Ze Ou, Kelly Jiang, Meghana Bhimreddy, Stuart J. Bauer, John N. Theodore, Victor M. Quiroz, Ian Suk, Safwan Alomari, Junfeng Sun, Shanbao Tong, Nitish Thakor, Joshua C. Doloff, Nicholas Theodore, Amir Manbachi

IEEE Transactions on Biomedical Engineering 2023, 70, 1992-2001 · 10.1109/tbme.2022.3233345

rodenthealthyemg mephistology molecular

Abstract

Objective Here we investigate the ability of low-intensity ultrasound (LIUS) applied to the spinal cord to modulate the transmission of motor signals. Methods Male adult Sprague-Dawley rats (n = 10, 250-300 g, 15 weeks old) were used in this study. Anesthesia was initially induced with 2% isoflurane carried by oxygen at 4 L/min via a nose cone. Cranial, upper extremity, and lower extremity electrodes were placed. A thoracic laminectomy was performed to expose the spinal cord at the T11 and T12 vertebral levels. A LIUS transducer was coupled to the exposed spinal cord, and motor evoked potentials (MEPs) were acquired each minute for either 5- or 10-minutes of sonication. Following the sonication period, the ultrasound was turned off and post-sonication MEPs were acquired for an additional 5 minutes. Results Hindlimb MEP amplitude significantly decreased during sonication in both the 5- (p Conclusion LIUS applied to the spinal cord suppresses MEP signals caudal to the site of sonication, with recovery of MEPs to baseline after sonication. Significance LIUS can suppress motor signals in the spinal cord and may be useful in treating movement disorders driven by excessive excitation of spinal neurons.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects10 animals
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsemg mep, histology molecularmotor evoked potentials (MEPs) in forelimb and hindlimb muscles; qPCR of immune/inflammation, neuromodulation and fibrosis genes; H&E and Masson's trichrome histology
Direction of effectinhibitoryHindlimb MEP amplitude significantly decreased during sonication of the spinal cord in both the 5- and 10-min cohorts, with gradual recovery to baseline after sonication; forelimb MEP amplitude (rostral to the sonication site) was unaffected.
Adverse eventsnone observedH&E and Masson's trichrome staining showed no detectable structural or morphological changes between sonicated and control spinal cords, qPCR showed no significant differences in immune/inflammatory, neuromodulatory or fibrosis genes, and temperature analysis showed minimal heating during sonication.

Exposures

Exposure 1: Low-intensity pulsed ultrasound to exposed dorsal spinal cord

Target: thoracic spinal cord — “exposed dorsal spinal cord at the T11 and T12 vertebral levels (laminectomy site)
Device: Olympus / Panametrics · Olympus Panametrics · V301

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)not reported
Duty cycle (%)50✓✓
Sonication duration (s)300, 600swept✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)29.7✓✓
Free-field Isppa (W/cm²)0.06✓✓
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
Protocol, in the paper’s words

All 10 rats received a 5-min sonication trial, and 5 of these rats also received an additional 10-min sonication trial after a 30-minute recovery period. Each trial comprised baseline, during-sonication, and post-sonication periods (1/5/5 min for the 5-min trial; 2/10/5 min for the 10-min trial), with MEPs acquired every minute.

Consistency checks: intensity pressure inconsistent free field.

Flags from extraction

  • exposures[0].timing.pulse_repetition_frequency_hzNot stated; only tone-burst duration (500 us) and duty cycle (50%) given, PRF would require arithmetic (duty/pulse duration) which was not performed.
  • n_sessions_per_subjectAll 10 rats received one 5-min sonication trial but only 5 of the 10 also received a second 10-min trial, so sessions per subject was not uniform and is not stated as a single number.
  • exposures[0].free_field.pressure_kpaPressure and intensity were measured in a water tank at the output aperture of the collimator; not explicitly labelled free-field vs in-situ, but no skull/tissue path was present between transducer and cord so free_field is used.