Potential impact of thermal effects during ultrasonic neurostimulation: retrospective numerical estimation of temperature elevation in seven rodent setups

In the past decade, a handful but growing number of groups have reported worldwide successful low intensity focused ultrasound induced neurostimulation trials on rodents. Its effects range from movement elicitations to reduction of anesthesia time or reduction of the duration of drug induced seizures. The mechanisms underlying ultrasonic neuromodulation are still not fully understood. Given the low intensities used in most of the studies, a mechanical effect is more likely to be responsible for the neuromodulation effect, but a clear description of the thermal and mechanical effects is necessary to optimize clinical applications. Based on five studies settings, we calculated the temperature rise and thermal doses in order to evaluate its implication in the neuromodulation phenomenon. Our retrospective analysis shows thermal rise ranging from 0.002 degrees C to 0.8 degrees C in the brain for all setups, except for one setup for which the temperature increase is estimated to be as high as 7 degrees C. We estimate that in the latter case, temperature rise cannot be neglected as a possible cause of neuromodulation. Simulations results were supported by temperature measurements on a mouse with two different sets of parameters. Although the calculated temperature is compatible with the absence of visible thermal lesions on the skin, it is high enough to impact brain circuits. Our study highlights the usefulness of performing thermal simulations prior to experiment in order to fully take into account not only the impact of the peak intensity but also pulse duration and pulse repetition.