Displacement-guided focused ultrasound for pain modulation.

Columbia University Health Sciences, New York NY

Investigators

Abstract

Over the past few years, focused ultrasound (FUS) has emerged as a promising noninvasive approach capable of both stimulating and suppressing neuronal activity. Ultrasound has several advantages over the aforementioned technologies as it can penetrate the brain over several centimeters through the intact scalp and skull. Given its entirely noninvasive and nonionizing nature, the technique has been shown to be translatable to human brain studies without requiring introduction of electrodes or optical fibers. Similarly, FUS has been applied noninvasively on peripheral nerves providing similar advantages. FUS works by modulating the neuronal tissue region where the FUS beam is focused and could be combined with readouts that inform level of activation. Several studies have shown that FUS can stimulate and/or suppress electrical and/or hemodynamic activity in rodents, non-human primates (NHP) and humans, induce limb movement, pupil dilation as well as suppression of somatosensory evoked potentials (SSEP) in mice evoke anti-saccades in NHP and suppress pain sensation in humans. In sharp contrast with its premise, however, and despite the multitude of advantages, FUS remains severely limited due to the lack of intra-animal reproducibility, lack of targeting and monitoring methodologies during modulation and its unknown underlying mechanism or targeted region. The true potential of FUS remains diminished in its expedited adoption and therefore risks faltering on its premise. To this purpose, our group has developed novel ultrasound-guided (USgFUS) capabilities with feasibility shown in both CNS and PNS FUS modulation. In the proposed studies, we aim to harness those methodologies developed to target regions critical for pain treatment. The methodologies proposed could thus constitute breakthroughs in FUS modulation since they allow to selectively focus (on the order of a few millimeters) and apply in shallow and deep-seated regions while informing on the type of FUS mechanism in real time.. In the proposed R18 study, we aim to harness the full potential of our novel monitoring system (MOTUS (MOnitoring of Transcranial UltraSound)) to improve both safety and efficacy of FUS that can be used to both target and image responses to both central (C-MOTUS) and peripheral (C-MOTUS) neuromodulation with FUS in rodents and primates. The novel ultrasound-based methodologies proposed herein would constitute breakthroughs in FUS modulation monitoring and allow for the first time accurately targeting (on the order of a few millimeters) and steering across both shallow and deep-seated regions (on the order of several centimeters in depth) as well as monitoring activity.