Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo
Ye-Hui Liao, Mo-Xian Chen, Shao-Chun Chen, Kai-Xuan Luo, Bin Wang, Yao Liu, Li-Juan Ao
Evidence-Based Complementary and Alternative Medicine 2021 · 10.1155/2021/8534466
Abstract
Although neurocircuits can be activated by focused ultrasound stimulation, it is unclear whether this is also true for spinal cord neurocircuits. In this study, we used low-intensity focused ultrasound (LIFU) to stimulate lumbar 4-lumbar 5 (L4-L5) segments of the spinal cord of normal Sprague Dawley rats with a clapper. The activation of the spinal cord neurocircuits enhanced soleus muscle contraction as measured by electromyography (EMG). Neuronal activation and injury were assessed by EMG, western blotting (WB), immunofluorescence, hematoxylin and eosin (H&E) staining, Nissl staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and the Basso-Beattie-Bresnahan locomotor rating scale. When the LIFU intensity was more than 0.5 MPa, LIFU stimulation induced soleus muscle contraction and increased the EMG amplitudes ( P P P β , TNF- α , and caspase-3 by IHC, ELISA, and WB ( P < 0.05). These results show that LIFU can activate spinal cord neurocircuits and that LIFU stimulation with an irradiation intensity ≤1.5 MPa is a safe neurostimulation method for the spinal cord.
Abstract via europepmc.
Exposures
Exposure 1: Lumbar L4-L5 spinal cord, 0.5-3.0 MPa
Target: lumbar spinal cord — “lumbar 4-lumbar 5 (L4-L5) segments of the spinal cord”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 4,000 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓⚑ |
| Duty cycle (%) | 20pulse duration × PRF gives 20% | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 500, 1,000, 1,500, 2,000, 2,500, 3,000swept | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.06, 0.18, 0.32, 0.4, 0.5, 0.6swept | ✓✓✓ |
| 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 |
Study I: 1 s ON / 4 s OFF stimulation per pressure level (20 s each) with 5 min between levels. Study II: 20 min of LIFU at 0, 0.5, 1.5 or 3.0 MPa. Each pulse was 800 cycles at 4 MHz.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Methods say 'cycles of 1000 Hz/s'; units unclear, taken as PRF 1000 Hz.exposures[0].timing.pulse_duration_ms— Only '800 cycles for every pulse period' at 4 MHz is stated; not converted.exposures[0].free_field.pressure_kpa— Acoustic pressure measured by hydrophone in a water tank (Methods 2.3), but values are listed as 'radiation intensity' in MPa; peak versus other pressure not stated.exposures[0].unspecified_domain.ispta_w_cm2— Ispta values in mW/cm2 stated without domain; converted to W/cm2.n_subjects— Study I n=6 and Study II n=42; overlap of animals not stated. Figures also give n=3 per assay.sham_type— 0 MPa group (LIFU-negative) received 'stimulation' at 0 MPa; mechanism not described.