Neuropathic Tissue Responds Preferentially to Stimulation by Intense Focused Ultrasound
Rowen E. Tych, Michael Gofeld, Jeffrey G. Jarvik, Michel Kliot, John D. Loeser, Abbi M. McClintic, Ryan J. Ollos, Kristin D. Pederson, Rachel E. Sparks, Gregory W. Terman, Pierre D. Mourad
Ultrasound in Medicine & Biology 2013, 39, 111-116 · 10.1016/j.ultrasmedbio.2012.08.012
Abstract
We tested the hypothesis that neuropathic tissue is more sensitive to stimulation by intense focused ultrasound (iFU) than control tissue. We created a diffusely neuropathic paw in rats via partial ligation of the sciatic nerve, whose sensitivity to iFU stimulation we compared with sham-surgery and normal control paws. We then applied increasing amounts of iFU (individual 0.2 s pulses at 1.15 MHz) to the rats' paws, assaying for their reliable withdrawal from that stimulation. Neuropathic rats preferentially withdrew their injured paw from iFU at smaller values of iFU intensity (84.2 W/cm(2) ± 25.5) than did sham surgery (97.7 W/cm(2) ± 11.9) and normal control (> 223 W/cm(2)) animals, with greater sensitivity and specificity (85% for neuropathic rats and 50% each of sham surgery and normal control rats). These results directly support our hypothesis as well as Gavrilov's idea that doctors may some day use iFU stimulation to diagnose patients with neuropathies.
Abstract via europepmc.
Exposures
Exposure 1: iFU paw-withdrawal threshold testing in partial sciatic nerve ligation (pSNL), sham-surgery and normal-control rats
Target: sciatic nerve — “the plantar surface of the paw”
Device: custom-built
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 1,150 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 84.2, 97.7, 223swept | ✓✓✓⚑ |
| 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 |
In the absence of a hind paw withdrawal response, the intensity of ultrasound was increased in increments beginning at approximately 30% of the previous intensity, tapering to 10%, starting with an initial acoustic intensity of approximately 10 W/cm2. After identification of the iFU threshold value, both hind paws were tested in a serial fashion for their withdrawal responses to that amount of iFU for an additional six iFU applications, with at least 30 s between each application.
Flags from extraction
n_subjects— Paper gives group sizes (33 pSNL, 30 sham, 12 normal control) but never states a combined total exposed to ultrasound, so group sizes are listed rather than summed.exposures[0].free_field.ispta_w_cm2— Value reported is the mean iFU threshold intensity found per group (Table 3), not a fixed applied stimulus level; the device's intensity was titrated up from about 10 W/cm2 in each session until a withdrawal threshold was reached.exposures[0].free_field.ispta_w_cm2— Paper reports intensity as I_SATA (spatially averaged, temporally averaged), which does not exactly match either the isppa or ispta schema fields; recorded here under ispta_w_cm2 as the closest match.anaesthesia— Surgery for the pSNL and sham groups was performed under deep isoflurane anesthesia, but the iFU behavioural testing itself (5-7+ days later) was performed on awake, unanesthetized animals; anaesthesia field reflects the testing condition.