Neuromodulation by Focused Ultrasound

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Neuromodulation by Focused Ultrasound (NeuroFUS) provides the highest spatial resolution of all the noninvasive neuromodulation methods. It is safe, effective, and works by mechanically modulating the activity of ion channels. In collaboration with strategic partners, we are developing brain applications for the treatment of mental health disorders and peripheral applications for the treatment of neurogenic pain.

The Spatial Resolution of Neuromodulation. Transcranial focused ultrasound (tFUS) for neuromodulation can achieve a spatial resolution equivalent to the spatial dimensions of electric fields generated by deep-brain stimulating electrodes as shown below. In the periphery, higher frequency FUS (i.e. 2.5 MHz) can achieve a spatial resolution for neuromodulation that exceeds that of surgically-implanted electrodes used to treat various types of pain and other neuro-inflammatory or auto-immune disorders.

The top panel of images shows a 0.5 MHz transcranial focused ultrasound (tFUS) beam used to noninvasively modulate the human thalamus (left). The two X-Z beam profiles shown on the right for 0.5 and 2.5 MHz are produced by NeuroFUS CTX-500 and mTX-2500 transducers. The right panel of images show the electric field produced by tDCS (top) and TMS (bottom). The bottom panel shows a pair of SCS electrodes (left). A common Medtronic DBS electrode is shown next to a DBS electric field model (right). The full width at half maximum (FWHM) at active electrode leads shown is ~ 4 mm, which is similar to the 5 mm FWHM for the 0.5 MHz tFUS beams shown in the top panel. As further illustrated, the 2.5 MHz neuromodulation FUS beam is geometrically smaller than the DBS electrode. tFUS image from Legon et al, 2018 and DBS field model modified from Buston and McIntyre, 2008.

Mechanisms of Action. Pulsed ultrasound can safely stimulate and suppress neuronal cellular activity. The core mechanisms responsible involve actions exerted by micro-mechanical pressure waves induced by low-intensity, pulsed ultrasound on ion channels. It has been shown that low-intensity, pulsed ultrasound modulates the activity of many voltage-gated channels (i.e. sodium and calcium), as well as mechano-sensitive channels (i.e. TRP, Piezo, and TREK) using our patented methods.

Next Steps. We are working with strategic partners to finalize the development of transcranial focused ultrasound (tFUS) for the treatment of depression and anxiety. As shown below, neuromodulation by tFUS confers numerous advantages over transcranial magnetic stimulation (TMS) that is already FDA-cleared for the treatment of depression with other billable indications emerging.