Focused Ultrasound Effects on Nerve Action Potential in vitro
Vincent Colucci, Gary Strichartz, Ferenc Jolesz, Natalia Vykhodtseva, Kullervo Hynynen
Ultrasound in Medicine & Biology 2009, 35, 1737-1747 · 10.1016/j.ultrasmedbio.2009.05.002
Abstract
Minimally invasive applications of thermal and mechanical energy to selective areas of the human anatomy have led to significant advances in treatment of and recovery from typical surgical interventions. Image-guided focused ultrasound allows energy to be deposited deep into the tissue, completely noninvasively. There has long been interest in using this focal energy delivery to block nerve conduction for pain control and local anesthesia. In this study, we have performed an in vitro study to further extend our knowledge of this potential clinical application. The sciatic nerves from the bullfrog (Rana catesbeiana) were subjected to focused ultrasound (at frequencies of 0.661 MHz and 1.986 MHz) and to heated Ringer's solution. The nerve action potential was shown to decrease in the experiments and correlated with temperature elevation measured in the nerve. The action potential recovered either completely, partially or not at all, depending on the parameters of the ultrasound exposure. The reduction of the baseline nerve temperature by circulating cooling fluid through the sonication chamber did not prevent the collapse of the nerve action potential; but higher power was required to induce the same endpoint as without cooling. These results indicate that a thermal mechanism of focused ultrasound can be used to block nerve conduction, either temporarily or permanently.
Abstract via europepmc.
Exposures
Exposure 1: Continuous-wave FUS at the fundamental frequency (0.661 MHz, FL)
Target: sciatic nerve, excised nerve — “excised bullfrog sciatic nerve”
Device: custom-built
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 661 | ✓✓✓ |
| Pulse duration (ms) | not applicable | ⚑ |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | 100 | ✓? |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 370, 400, 440, 470, 650swept | ✓✓✓ |
| 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 |
Sonications were mostly continuous wave exposures. Groups receiving sonication were given a 30 s exposure, followed by a 60 s 'off' period, then a new sonication at an increased acoustic power, repeated until the action potential was eliminated or the maximum power was reached; experiments were repeated if the action potential recovered. In addition, 26 experiments in five nerves used burst sonication (burst length 1 or 10 ms, repetition frequency 10 or 20 Hz) to test reducing the time-average power.
Exposure 2: Continuous-wave FUS at the third-harmonic frequency (1.986 MHz, FH)
Target: sciatic nerve, excised nerve — “excised bullfrog sciatic nerve”
Device: custom-built
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 1,986 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | 100 | ✓? |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 418, 875swept | ✓✓✓ |
| 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 |
Sonications were mostly continuous wave exposures. Groups receiving sonication were given a 30 s exposure, followed by a 60 s 'off' period, then a new sonication at an increased acoustic power, repeated until the action potential was eliminated or the maximum power was reached; experiments were repeated if the action potential recovered. In addition, 26 experiments in five nerves used burst sonication (burst length 1 or 10 ms, repetition frequency 10 or 20 Hz) to test reducing the time-average power.
Flags from extraction
exposures[0].unspecified_domain.ispta_w_cm2— Intensity was calibrated via hydrophone/radiation-force measurement in the transducer's water coupling column, not explicitly labelled as free-field or in-situ; placed in unspecified_domain.exposures[1].unspecified_domain.ispta_w_cm2— Same domain ambiguity as the low-frequency exposure; recorded in unspecified_domain.exposures[0].unspecified_domain.ispta_w_cm2— This was a continuous dose-escalation protocol; many more intensity values appear across the text and figures (e.g. 100-200, 300-350, 470 W/cm2) than the illustrative examples captured here.exposures[0].timing.pulse_duration_ms— A secondary burst-sonication sub-experiment (burst length 1 or 10 ms, PRF 10 or 20 Hz) was also performed at both frequencies but is not captured in the numeric timing fields, which describe the primary continuous-wave protocol; see protocol_description.