Acoustic frequency-dependent physical mechanism of sub-MHz ultrasound neurostimulation
Haixiao Fan, Kenta Shimba, Ayumu Ishijima, Kenya Sasaoka, Tsuyoshi Takahashi, Eigo Saka, Chih-Hsiang Chang, Yasuhiko Jimbo, Takashi Azuma, Shu Takagi
Japanese Journal of Applied Physics 2022 · 10.35848/1347-4065/ac9faf
Abstract
Ultrasound allows non-invasive and reversible modulation of neural circuit activity with high spatial resolution. Despite growing interest in clinical applications, the safe and effective use of ultrasound neuromodulation has been limited by a lack of understanding of the physical mechanisms underlying its effects. Here, we demonstrate acoustic frequency-dependent physical effects that underlie ultrasound neuromodulation, where cavitation and radiation forces are the dominant sources of low- and high-frequency stimulation, respectively. We used 39.5 and 500 kHz acoustic frequencies to stimulate cultured neural and glial cells to study acoustic frequency-dependent neural responses. We demonstrate increased evoked responses due to increased cavitation activity at the 39.5 kHz acoustic frequency. In contrast, notable cavitation activity was not detected at 500 kHz despite detection of evoked responses. Our work highlights the dependence of ultrasound neuromodulation on acoustic frequencies, with different physical effects underlying cell responses to low and high sub-MHz acoustic frequency ranges.
Abstract via crossref.
Exposures
Exposure 1: 39.5 kHz unfocused transducer
Target: cultured neurons, cultured glia — “cells cultured from rat cortex”
Device: other named manufacturer · Fuji Ceramics Corporation · FBL40152SSF-FC ✓
| Waveform | not reported | |
|---|---|---|
| Fundamental frequency (kHz) | 39.5 | ✓✓✓ |
| Pulse duration (ms) | 41.7 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | not reported |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 0.002, 0.049swept | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
Sinusoidal drive with a pulse duration of 41.7 ms; intensity changed stepwise with 3 min between changes. Number of pulses per intensity and any repetition rate are not stated in the text.
Exposure 2: 500 kHz unfocused transducer
Target: cultured neurons, cultured glia — “cells cultured from rat cortex”
Device: other named manufacturer · Japan Probe · 0.5K1OI ✓
| Waveform | not reported | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 41.7 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | not reported |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 0.09, 0.55swept | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
Sinusoidal drive with a pulse duration of 41.7 ms; intensity changed stepwise with 3 min between changes. Number of pulses per intensity and any repetition rate are not stated in the text.
Flags from extraction
exposures[0].free_field.isppa_w_cm2— Intensities were calculated from pressure measured in a water tank under progressive-wave conditions; the cultures were exposed in standing-wave conditions, so cell exposure is higher than stated. Recorded as free_field.exposures[1].free_field.isppa_w_cm2— Same standing-wave caveat as exposures[0].exposures[0].timing— Only a 41.7 ms pulse duration is stated; PRF, number of pulses and sonication duration are not given in the text (timing schematic is Fig. 2b). Waveform left not_reported.n_subjects— N = 6 dishes is stated in figure captions (Figs 3 and 4); whether the same count applies to both frequencies is not stated.exposures[0].device.family— Transducers named with a supplier and part number only; classed other_manufacturer.auditory_control— Paper uses cell culture to avoid off-target auditory responses but no auditory control is described.