It is known that focused ultrasound energy in the 1-10 MHz medical diagnostic region of frequencies can stimulate bioelectrically excitable tissues such as nerves, brain tissue, and cardiac muscle cells. The reason for its effectiveness is thought to be due to pressure and stretch effects on cell membranes leading to intracellular sodium ion influx. Unfortunately, the bioelectric interaction mechanism of ultrasound with tissue at these frequencies is inefficient. At 7 MHz it requires relatively high ultrasound power levels to excite nerve, near tissue damage thresholds, and bulky transducers; therefore, this approach has seen little application. It has recently become possible however, to practically generate high frequency ultrasound in the 50-150 MHz region. A hypothesis of this work is that, for reasons based on both physiological theory as well as ultrasound physics, these relatively high frequencies should be much more effective in producing bioelectric stimulation effects. At the same time, high frequencies allow the use of millimeter-sized ultrasound transducers that can concentrate their energy in extremely small focal zones; near ten micron cellular dimensions. Ultrasound energy has a different interaction physics with excitable tissue than does electricity, leading to a number of unexplored possible advantages including the potential for less invasive stimulation as well as highly spatially selective stimulation of near cellular scale structures. The proposed work will compare high frequency ultrasound stimulation of peripheral nerve to that achieved by electrical stimulation using a rabbit model. Ultrasound functional activation of the sciatic nerve will be monitored by measuring developed hindleg muscle force and compared using muscle recruitment curves to that achieved by electrical activation. The work will evaluate the possibility of highly focal stimulation of individual nerve fibers in a bundle using the focal nature of ultrasound. Although very high frequency ultrasound has limited range in tissue, there are applications where small, potentially millimeter-order sized high frequency ultrasound transducers could be preferable to the use of conventional stimulating electrodes. In principle, improved and more effective ultrasound bioelectric-stimulation instrumentation could have broad utility in medical, biological, and electrophysiological studies.
