Displacement Imaging for Focused Ultrasound Peripheral Nerve Neuromodulation.

Focused ultrasound (FUS) is an emerging technique for neuromodulation due to its noninvasive application and high depth penetration. Recent studies have reported success in modulation of brain circuits, peripheral nerves, ion channels, and organ structures. In particular, neuromodulation of peripheral nerves and the underlying mechanisms remain comparatively unexplored in vivo. Lack of methodologies for FUS targeting and monitoring impede further research in in vivo studies. Thus, we developed a method that non-invasively measures nerve engagement, via tissue displacement, during FUS neuromodulation of in vivo nerves using simultaneous high frame-rate ultrasound imaging. Using this system, we can validate, in real-time, FUS targeting of the nerve and characterize subsequent compound muscle action potentials (CMAPs) elicited from sciatic nerve activation in mice using 0.5 to 5 ms pulse durations and 22 - 28 MPa peak positive stimulus pressures at 4 MHz. Interestingly, successful motor excitation from FUS neuromodulation required a minimum interframe nerve displacement of 18 μm without any displacement incurred at the skin or muscle levels. Moreover, CMAPs detected in mice monotonically increased with interframe nerve displacements within the range of 18 to 300 μm . Thus, correlation between nerve displacement and motor activation constitutes strong evidence FUS neuromodulation is driven by a mechanical effect given that tissue deflection is a result of highly focused acoustic radiation force.