Intense Focused Ultrasound Preferentially Stimulates Transected Nerves Within Residual Limbs: Pilot Study
Pierre D Mourad, Janna L Friedly, Abbi M McClintic, Tessa A Olmstead, John D Loeser
Pain Medicine 2018 · 10.1093/pm/pnx188
Abstract
Objective Identifying pain generators in tissue deep in the skin can require uncomfortable, complicated, and invasive tests. We describe pilot studies testing the hypothesis that ultrasound image-guided, intense focused ultrasound (ig-iFU) can noninvasively and differentially stimulate the end of transected nerves in the residual limbs of amputee patients. Design We applied iFU to the transected nerve ending as individual pulses with a length of 0.1 seconds using a carrier frequency of 2.0 MHz. After targeting, we gradually increased the iFU intensity to reach consistent patient-reported stimulation of the transected nerve ending. We also stimulated the proximal nerve, tissue near the nerve ending, and the intact contralateral nerve. We described the resulting sensations and correlated the results of the study participant's pre-iFU study responses to phantom and residual limb pain questionnaires. Results iFU spatial and temporal average intensity values between 16 W/cm2 and 433 W/cm2 that were applied to the transected nerve ending and proximal nerve elicited sensations, including phantom limb sensations, while the same intensity applied to control tissue centimeters away from the nerve ending, or to the intact nerve on the contralateral limb, did not. Two out of 11 study participants reported only mild and transient pain created by iFU stimulation. Successful iFU intensity values correlated with neither phantom nor residual limb pain scores. Conclusions Transected nerves had greater sensitivity to iFU stimulation than ipsilateral and contralateral control tissue, including intact nerve. These results support the view that ig-iFU may one day help physicians identify deep, tender tissue in patients who report experiencing pain.
Abstract via europepmc.
Exposures
Exposure 1: Image-guided iFU to transected nerve ending (and proximal nerve, control tissue, contralateral nerve)
Target: nerve injury site — “the transected nerve ending”
Device: custom-built · five 2.0 MHz iFU transducers with foci at 0.4, 1.3, 2.45, 2.75 and 3.0 cm
| 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 reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 16, 433swept | ✓?⚑ |
Three to five individual 0.1-second bursts at approximately 1 Hz, intensity raised stepwise from 16 W/cm2 until a reliable sensation (two consecutive sets); maximum device output 1,032 W/cm2.
Flags from extraction
n_subjects— Results text mentions 11/13 participants with LANSS above 12, inconsistent with 11 participants stated elsewhere.exposures[0].unspecified_domain.ispta_w_cm2— Range 16-433 W/cm2 is the threshold values reported in the abstract; intensities were stepped up to a device maximum of 1,032 W/cm2. Calibrated in water by hydrophone but values not stated to be free-field.exposures[0].device.family— Paper says the five transducers were created by the authors, maker not named; custom_built chosen.sham_type— Sham-applied iFU is mentioned but its mechanism is not described; control tissue and contralateral nerve also stimulated actively.exposures[0].timing.waveform— Single 0.1 s burst per application, no internal gating described; recorded as continuous.