Intense focused ultrasound can reliably induce sensations in human test subjects in a manner correlated with the density of their mechanoreceptors

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.

Figure 1

Our ultrasound delivery device. The transducer itself is embedded within an aluminum housing.

Figure 2

A beam plot of intensity along the axis the device used in the study. The primary focus occurs near the tip of the cone, with a secondary maximum of one-fourth the intensity at the surface measured 0.75 cm below the skin.

Figure 3

Beam plot showing the iFU intensity as a function of radial distance out from the center of the transducer face.

Figure 4

A plot of the test subjects’ sensitivity as a function of intense focused ultrasound (iFU) intensity value. The drop in sensitivity at 170 W/cm² is due to a reduction in available data for plotting, itself caused by our cessation of data collection for many subjects due to their completion of the study. (See Figure 5 below for examples of individual contributions to this aggregate data plot.) The numbers next to data points denote the number of individual data points contributing to that average point on the graph.

Figure 5

A plot showing the sensitivity versus the intensity values of our stimulating intense focused ultrasound (iFU), here for two of our test subjects. The first reached the 90% threshold for sensitivity at relatively low values of iFU intensity. The second reached their 90% threshold for sensitivity at a relatively large value of iFU intensity.

Figure 6

A curve plotting how a given population reaches both a 90% as well as a 50% threshold as a function of intense focused ultrasound (iFU) intensity. All test subjects reached a value of 50% sensitivity while seventy percent of our test subjects reached a value of 90% sensitivity.

Figure 7

A statistically significant correlation exists between the intense focused ultrasound (iFU) intensity required for our test subjects to achieve each of a 90% and 50% sensitivity threshold value and the two-point assay of their density of peripheral nerve receptors. Here, that density is inversely proportional to the distance (reported here in millimeters) between two successfully identified stimulation points by the DISK-CRIMINATOR^™.