Strategies and safety simulations for ultrasonic cervical spinal cord neuromodulation

Focused ultrasound spinal cord neuromodulation studies have demonstrated spinal cord neuromodulation in small animals. The safe and efficacious translation of these approaches to human scale requires an understanding of ultrasound propagation and heat deposition within the human spine. To address this, combined acoustic and thermal modelling was used to assess the pressure and heat distributions produced by a 500 kHz source focused to the C5/C6 level of the cervical spine via two approaches a) the posterior acoustic window between vertebral posterior arches, or b) the lateral intervertebral foramen from which the C6 spinal nerve exits. Pulse trains of 150 0.1 s pulses with a pulse repetition frequency of 0.33 Hz and free-field spatial peak pulse-averaged intensity of 10 W/cm^2 were simulated for the CT volumes of four subjects and for $\pm$10 mm translational and $\pm$10{\deg} rotational source positioning errors. Target pressures ranged between 20% and 70% of free-field spatial peak pressures with the posterior approach, and 20% and 100% with the lateral approach. When the source was optimally positioned with the posterior approach, peak spine heating values were below 1{\deg}C, but source mis-positioning resulted in bone heating up to 4{\deg}C. Heating with the lateral approach did not exceed 2{\deg}C within the mispositioning range. There were substantial inter-subject differences in target pressures and peak heating values. Target pressure varied three to four-fold between subjects, depending on approach, while peak heating varied approximately two-fold between subjects. This results in a near ten-fold range in the target pressure achieved per degree of peak heating between subjects. This highlights the importance of developing trans-spine ultrasound simulation software for the assurance of subject-specific safety and efficacy of focused ultrasound spinal cord therapies.