Intense Focused Ultrasound Can Reliably Induce Sensations in Human Test Subjects in a Manner Correlated With the Density of Their Mechanoreceptors
Trevor C. Dickey, Rowen Tych, Michel Kliot, John D. Loeser, Kristin Pederson, Pierre D. Mourad
Ultrasound in Medicine & Biology 2012, 38, 85-90 · 10.1016/j.ultrasmedbio.2011.09.020
Abstract
Sensations generated by intense focused ultrasound (iFU) can occur cutaneously and/or at depth, in contrast to other forms of stimulation (e.g., heat, electricity), whose action usually occurs only at the skin surface, or mechanical stimulation (e.g., von Frey hairs, calibrated forceps, tourniquets) that compress and thus stimulate all tissue. Previous work on iFU stimulation has led to the hypothesis that the tactile basis of iFU stimulation should correlate with the density of mechanoreceptors at the site of iFU stimulation. Here we tested that hypothesis, correlating a "two-point" neurological examination-a standard measure of superficial mechanoreceptor density-with the intensity of superficially applied iFU necessary to generate sensations with high sensitivity and specificity. We applied iFU at 1.1 MHz for 0.1 s to the fingertip pads of 17 test subjects in a blinded fashion and escalated intensities until they consistently observed iFU-induced sensations. Most test subjects achieved high values of sensitivity and specificity, doing so at values of spatially and temporally averaged intensity measuring <100 W/cm(2). Moreover, the test subjects' sensitivity to iFU stimulation correlated with the density of mechanoreceptors as determined by a standard two-point discrimination neurological examination, consistent with earlier hypotheses.
Abstract via europepmc.
Exposures
Exposure 1: iFU stimulation of the fingertip pad (intensity titration for sensation detection)
Target: digital nerve — “fingertip pad (index finger)”
Device: custom-built · solid cone device (custom aluminum housing with commercial flat piezoelectric transducer)
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 1,117 | ✓✓✓⚑ |
| 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) | 106.4 | ✓✓✓ |
For all experiments a single 100-ms pulse of ultrasound was delivered to the fingertip pad. Using the method of ascending limits, iFU intensity was systematically increased (data binned in 30 W/cm2 increments for graphing) across trials of 20 applications (10 real, 10 sham) per intensity value until a subject reported 9 of 10 true positives (90% threshold), the output reached a ceiling of 650 W/cm2 (a value from separate animal studies shown to produce reliable, safe sensations), or time ran out for that subject; testing was repeated on a second day at least one week later.
Flags from extraction
exposures[0].fundamental_frequency_khz— Abstract rounds the frequency to '1.1 MHz'; the precise Methods value (1.117 MHz) was used.sham_type— The paper states sham vs real trials were randomized and subjects blinded, but never describes what a 'sham' application physically consisted of (e.g. transducer powered off, blocked, or aimed away); recorded as other.exposures[0].unspecified_domain.isppa_w_cm2— The paper's own intensity metric is described as 'spatially and temporally averaged' over the beam area (not a spatial-peak quantity), so its correspondence to the schema's Isppa/Ispta definitions is approximate; also, domain (free-field vs at-skin) is not stated, so values are placed in unspecified_domain. List combines the 90% (106.4 W/cm2) and 50% (95 W/cm2) threshold means, each stated in a separate sentence; the quoted sentence documents the 106.4 W/cm2 value only.exposures[0].timing.duty_cycle_pct— Left null because the stimulus is a single, non-repeated 100 ms burst per trial (classified as waveform=continuous per the single-uninterrupted-burst rule); duty cycle as a percentage is not meaningful/stated for a solitary pulse.adverse_events— Coded 'observed' based on 5 of 34 test sessions in which subjects reported transient pain (median NRS 1/10); no lasting effects or tissue injury were reported.