In vitro single-unit recordings reveal increased peripheral nerve conduction velocity by focused pulsed ultrasound
S J Ilham, L Chen, T Guo, S Emadi, K Hoshino, B Feng
Biomedical Physics & Engineering Express 2018 · 10.1088/2057-1976/aabef1
Abstract
Ultrasound that is widely used in medical diagnosis has drawn growing interests as a noninvasive means of neuromodulation. Focused pulsed ultrasound (FPUS) effectively modulates neural encoding and transmission in the peripheral nervous system (PNS) with unclear mechanism of action, which is further confounded by contradictory experimental outcomes from recordings of compound action potentials (CAP). To address that, we developed a novel in vitro set up to achieve simultaneous single-unit recordings from individual mouse sciatic nerve axon and systematically studied the neuromodulation effects of FPUS on individual axon. Unlike previous CAP recordings, our single-unit recordings afford superior spatial and temporal resolution to reveal the subtle but consistent effects of ultrasonic neuromodulation. Our results indicate that, 1) FPUS did not evoke action potentials directly in mouse sciatic nerve at all the tested intensities (spatial peak temporal average intensity, I SPTA of 0.91 to 28.2 W/cm 2 ); 2) FPUS increases the nerve conduction velocity (CV) in both fast-conducting A- and slow-conducting C- type axons with effects more pronounced at increased stimulus duration and intensity; and 3) effects of increased CV is reversible and cannot be attributed to the change of local temperature. Our results support existing theories of non-thermal mechanisms underlying ultrasonic neuromodulation with low-intensity FPUS, including NICE, flexoelectricity, and solition models. This work also provides a solid experimental basis to further advance our mechanistic understandings of ultrasonic neuromodulation in the PNS.
Abstract via europepmc.
Exposures
Exposure 1: Focused pulsed ultrasound to excised mouse sciatic nerve, 1.1 MHz
Target: excised nerve, sciatic nerve — “the ~2 mm middle segment of the sciatic nerve”
Device: Sonic Concepts · Sonic Concepts · H-101G ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,100 | ✓✓✓ |
| Pulse duration (ms) | 0.0002 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 200,000 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 4% | |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.91, 2.99, 14.5, 28.2swept | ✓✓✓ |
| 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 |
90 electrical stimuli at 0.5 Hz: 20 pre-US, 20 during US (FPUS for 40 s), 50 post-US; one intensity per protocol with at least 5 min between protocols.
Flags from extraction
exposures[0].timing.pulse_duration_ms— The 200 ns / 200 kHz figures describe the electrical square pulses to the amplifier; the transducer response is stated as several cycles, about 6 microseconds. Converted 200 ns to 0.0002 ms as written.exposures[0].unspecified_domain.ispta_w_cm2— Intensity from hydrophone-derived calculation in a water chamber; domain not explicitly named. Text also mentions 65.2/65.5 and 102.31 W/cm2 for temperature and histology only.n_subjects— 62 fibres from 15 mice for the main protocol; 4 further nerves used for histology.exposures[0].unspecified_domain.ispta_w_cm2— Conclusion lists 0.99 W/cm2 in places, results text lists 0.91; 0.91 recorded.