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 (heat, electricity) whose action usually occurs only at the skin surface or mechanical stimulation (von Frey hairs, calibrated forceps, tourniquets) that compress, hence 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 exam, 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 a 0.1 second to the fingertip pads of seventeen test subjects in a blinded fashion and escalating 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 less than 100 W/cm^2. Moreover, the test subject’s sensitivity to iFU stimulation correlated with the density of mechanoreceptors as determined by a standard two-point discrimination neurological exam, consistent with earlier hypotheses.

Rapid ultrasonic stimulation of inflamed tissue with diagnostic intent

“…This is a functional measure of the iFU safety; the rat's response to a standard heat source did not change after iFU application. This amount of iFU is also consistent with that applied to humans by a variety of authors (Dickey et al, 2012;Dalecki et al, 1995;Gavrilov et al, 1977a,b;Gavrilov et al, 1996). Also, our recent work (Garcia et al, 2013) showed that the iFU stimulation threshold generated by single pulses of iFU for inflamed tissue tracks the known diurnal component of inflammatory pain.…”

“…This means that sufficiently intense focused ultrasound-known as HIFU for "high intensity focused ultrasound"-is a promising therapeutic modality (Illing et al, 2005;Klinger et al, 2008;Park et al, 2009). However, in lesser amounts, iFU has induced discernable sensations in human subjects (Gavrilov et al, 1977a,b;Gavrilov et al, 1996;Dalecki et al, 1995;Wright et al 2002;Dickey et al, 2012).…”

Neuropathic Tissue Responds Preferentially to Stimulation by Intense Focused Ultrasound

“…We used a commercial piezo-electric, flat transducer built into a custom solid, cylindrical cone-shaped aluminum housing (described in Miao et al, 2005 and Dickey et al, 2012) to determine the amount of iFU necessary to cause the rats to withdraw their paws in response to iFU stimulation. We created the iFU signal (individual ultrasound pulses with a center frequency of 1.15 MHz, each lasting for 0.2 seconds) with two function generators (HP33120A, Hewlett-Packard, Palo Alto, CA), amplified by a power amplifier (ENI A150, ENI, Rochester, NY) whose signal we transmitted directly to the transducer.…”

“…Several groups of researchers have shown that sufficiently intense focused ultrasound (iFU) can generate sensations in healthy test subjects when applied to tissue both superficially and at depth (Dalecki et al 1995; Dickey et al, 2012; Gavrilov et al 1977a,b; Gavrilov et al 1996; Gershuni et al 1980; and Wright et al 1993, 2002) likely through mechanical stimulation, at least at threshold values of iFU (reviewed in Gavrilov et al, 1996). Therefore, as hypothesized originally by Gavrilov and colleagues, it is plausible that iFU stimulation of neuropathic tissue could generate diagnostically useful sensations because those sensations may differ in quality or intensity compared to sensations generated by iFU stimulation of normal tissue.…”

Intense Focused Ultrasound Stimulation of the Rotator Cuff: Evaluation of the Source of Pain in Rotator Cuff Tears and Tendinopathy

“…It has further been found that iFU can stimulate focal and subcutaneous neuromas at doses that do not stimulate normal surrounding tissue . Finally, iFU can generate reliably sensed, cutaneous sensations in humans (Dickey et al 2012).…”