Intense Focused Ultrasound Preferentially Stimulates Subcutaneous and Focal Neuropathic Tissue: Preliminary Results
Abbi M. McClintic, Trevor C. Dickey, Michael Gofeld, Michel Kliot, John D. Loeser, Philippe Richebe, Pierre D. Mourad
Pain Medicine 2013, 14, 84-92 · 10.1111/j.1526-4637.2012.01510.x
Abstract
Objective Potential peripheral sources of pain from subcutaneous tissue can require invasive evocative tests for their localization and assessment. Here, we describe studies whose ultimate goal is development of a noninvasive evocative test for subcutaneous, painful tissue. Design We used a rat model of a focal and subcutaneous neuroma to test the hypothesis that intense focused ultrasound can differentiate focal and subcutaneous neuropathic tissue from control tissue. To do so, we first applied intense focused ultrasound (2 MHz, with individual pulses of 0.1 second in duration) to the rat's neuroma while the rat was under light anesthesia. We started with low values of intensity, which we increased until intense focused ultrasound stimulation caused the rat to reliably flick its paw. We then applied that same intense focused ultrasound protocol to control tissue away from the neuroma and assayed for the rat's response to that stimulation. Results Intense focused ultrasound of sufficient strength (I(SATA) of 600 +/- 160 W/cm(2) ) applied to the neuroma caused the rat to flick its paw, while the same intense focused ultrasound applied millimeters to a centimeter away failed to induce a paw flick. Conclusion Successful stimulation of the neuroma by intense focused ultrasound required colocalization of the neuroma and intense focused ultrasound supporting our hypothesis.
Abstract via europepmc.
Exposures
Exposure 1: iFU stimulation of the tibial neuroma vs. nearby control tissue
Target: tibial nerve, nerve injury site — “the rat's neuroma”
Device: Sonic Concepts · Sonic Concepts ✓
| 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) | 343 | ✓✓✓⚑ |
| 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 |
Beginning at 150 W/cm2, we applied 100-millisecond bursts of iFU to the neuroma while increasing the intensity in steps of 10-30% until the rat flicked its paw after application of iFU. The device focus was positioned 2 mm below the skin at the site of successful mechanical (von Frey) localization of the neuroma; the same intensity was then applied to a control site approximately 1 cm away.
Flags from extraction
exposures[0].free_field.ispta_w_cm2— Abstract reports a mean iFU threshold intensity of 600 +/- 160 W/cm2, but the Results section reports 343 +/- 77 W/cm2 for the subset of 21 tests with both mechanical and iFU thresholds found; both explicit values are listed here and the discrepancy should be checked against the source.exposures[0].free_field.ispta_w_cm2— The paper reports intensity as I_SATA (spatially averaged, temporally averaged), which does not exactly match either the isppa (spatial-peak pulse-average) or ispta (spatial-peak temporal-average) schema fields; recorded here under ispta_w_cm2 as the closest match.n_subjects— Surgery to create a neuroma was performed on 15 rats, but only 8 rats were reported as being tested with iFU in the Results section (plus 4 additional rats used in an earlier, separately described pilot study); n_subjects reflects only the 8 rats in the formal iFU test dataset.