A Pre-clinical Study of the Response Threshold of Intact and Transected Nerves to Stimulation by Transcutaneous Intense Focused Ultrasound
MS Bobola, CK Ezeokeke, K Kuznetslova, AC Lahti, JD Loeser, TA Olmstead, JL Friedly, PD Mourad
Ultrasound in Medicine & Biology 2019 · 10.1016/j.ultrasmedbio.2019.04.014
Abstract
We used diagnostic ultrasound imaging to guide individual bursts (0.1 s) of 2 MHz intense focused ultrasound (iFU) to determine the sensitivity of intact and transected nerves. We found that all nerves had greater sensitivity to iFU stimulation than surrounding muscle. Intact nerves from healthy volunteers had less sensitivity to iFU stimulation (272 ± 35 W/cm2 [median ± standard error]) than transected nerves (19 ± 37 W/cm2). Intact, contralateral nerves of amputees dichotomized naturally into two groups-one very sensitive to iFU stimulation (6 ± 2 W/cm2) and one relatively insensitive (539 ± 19 W/cm2), compared with the intact nerves of healthy volunteers. Our study demonstrates the ability of iFU under ultrasound image guidance to stimulate deep, intact and transected peripheral nerves. It also highlights differences in the receptivity to ultrasound stimulation of the peripheral nerves of amputees versus healthy volunteers.
Abstract via pubmed.
Exposures
Exposure 1: Image-guided iFU stimulation of peripheral nerves (intact and transected)
Target: median nerve, sciatic nerve, tibial nerve, peroneal nerve — “median, sciatic, tibial and peroneal nerves (intact and transected)”
Device: custom-built · custom-made iFU stimulation transducer (5 cm aperture, 4 cm focal length), guided by a Philips EPIQ 5 diagnostic imaging system ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.1 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not applicable | |
| Free-field Ispta (W/cm²) | 5, 820swept | ✓✓✓⚑ |
| 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 |
We applied iFU in five individual 0.1-s bursts, at approximately 0.5-1 Hz, to the target nerve, starting from a low intensity (~16 W/cm2) and increasing until a sensation was reported or the device maximum (820 W/cm2) was reached, defining the iFU intensity threshold (iFU_t).
Flags from extraction
exposures[0].target— Same 2 MHz iFU protocol was applied to several different nerves (median, sciatic, tibial, peroneal) at both intact and transected sites; represented as one exposure with multiple target terms rather than splitting into near-identical entries.exposures[0].free_field.ispta_w_cm2— 5-820 W/cm2 is the overall device/study range (starting ~16 W/cm2, device maximum 820 W/cm2, discussion states 5-820 W/cm2); individual per-nerve mean/median thresholds are study outcomes (see tables), not the applied exposure setting, so were not placed here.exposures[0].timing.waveform— Classified as a single continuous 0.1 s tone burst per trial (repeated as 5 separate bursts at ~0.5-1 Hz inter-trial rate), following the schema's example for an uninterrupted burst with no internal pulsing; PRF/duty cycle fields left null accordingly.