Effective Ultrasonic Stimulation in Human Peripheral Nervous System
Thomas Riis, Jan Kubanek
IEEE Transactions on Biomedical Engineering 2022, 69, 15-22 · 10.1109/tbme.2021.3085170
Abstract
Objective Low-intensity ultrasound can stimulate excitable cells in a noninvasive and targeted manner, but which parameters are effective has remained elusive. This question has been difficult to answer because differences in transducers and parameters-frequency in particular-lead to profound differences in the stimulated tissue volumes. The objective of this study is to control for these differences and evaluate which ultrasound parameters are effective in stimulating excitable cells. Methods Here, we stimulated the human peripheral nervous system using a single transducer operating in a range of frequencies, and matched the stimulated volumes with an acoustic aperture. Results We found that low frequencies (300 kHz) are substantially more effective in generating tactile and nociceptive responses in humans compared to high frequencies (900 kHz). The strong effect of ultrasound frequency was observed for all pressures tested, for continuous and pulsed stimuli, and for tactile and nociceptive responses. Conclusion This prominent effect may be explained by a mechanical force associated with ultrasound. The effect is not due to heating, which would be weaker at the low frequency. Significance This controlled study reveals that ultrasonic stimulation of excitable cells is stronger at lower frequencies, which guides the choice of transducer hardware for effective ultrasonic stimulation of the peripheral nervous system in humans.
Abstract via europepmc.
Exposures
Exposure 1: 300 kHz stimulation of index finger receptors/nerve endings
Target: digital nerve — “index finger (receptors and nerve endings)”
Device: Sonic Concepts · Sonic Concepts · H-115 ✓
| Waveform | continuous, pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 300 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 100, 20sweptpulse duration × PRF gives 20% | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 660, 1,000, 1,330swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 13, 29.8, 52.6swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | 2.6, 6, 10.5, 13, 29.8, 52.6swept | ✓✓✓ |
| 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 |
The stimuli were either continuous (200 ms of tone burst) or pulsed at 100 Hz at 20% duty (i.e., 2 ms on, 8 ms off, 2 ms on, etc., for 200 ms). The continuous and pulsed stimuli had the same pressure amplitude. There were 10 repetitions of the 12 stimuli, producing a total of 120 stimulation trials per subject. The stimuli were delivered every 8-12 s.
Exposure 2: 900 kHz stimulation of index finger receptors/nerve endings
Target: digital nerve — “index finger (receptors and nerve endings)”
Device: Sonic Concepts · Sonic Concepts · H-115 ✓
| Waveform | continuous, pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 900 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 100, 20sweptpulse duration × PRF gives 20% | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 750, 1,130, 1,500swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 16.7, 38, 67swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | 3.3, 7.6, 13.4, 16.7, 38, 67swept | ✓✓✓ |
| 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 |
The stimuli were either continuous (200 ms of tone burst) or pulsed at 100 Hz at 20% duty (i.e., 2 ms on, 8 ms off, 2 ms on, etc., for 200 ms). The continuous and pulsed stimuli had the same pressure amplitude. There were 10 repetitions of the 12 stimuli, producing a total of 120 stimulation trials per subject. The stimuli were delivered every 8-12 s.
Flags from extraction
exposures[*].unspecified_domain— Peak pressures/ISPPA were measured with a hydrophone in a water bath at the aperture; paper does not explicitly label this as a 'free field' measurement (impedance for intensity calculation used skin, not water), so the domain is left unspecified rather than assigned to free_field.exposures[*].unspecified_domain.ispta_w_cm2— ISPTA differs between continuous (equal to ISPPA) and pulsed (20% of ISPPA) conditions for each pressure level (Table II); this cannot be represented unambiguously as a single list aligned with the pressure list, so it is left not_reported. See Table II in the text for the six per-condition ISPTA values (2.6-52.6 W/cm2 for 300 kHz, 3.3-67.0 W/cm2 for 900 kHz).exposures[*].timing.duty_cycle_pct— List order is [continuous=100, pulsed=20]; pulse_duration_ms (2 ms) and pulse_repetition_frequency_hz (100 Hz) apply only to the pulsed condition, not to continuous.readout_timing— Classified as 'online' because subjects verbally reported a percept immediately after each brief (200 ms) stimulus; paper does not use the terms 'online'/'offline'.exposures[*].in_situ— The finger/water interface is described as acoustically transparent (~99.6% transmission); the paper never reports an absolute in-situ pressure or intensity value distinct from the aperture measurement, so in_situ fields are not_reported rather than null even though a (near-transparent) tissue path exists.