System for controlled mechanical therapies of the brain

Transcranial focused ultrasound enables remote targeted therapies that were previously only possible using surgical approaches. Mechanical therapies are particularly attractive due to their confined action and the elimination of the potentially harmful tissue and skull heating. However, systems for controlled mechanical therapies of the brain have been missing. Here, we have developed a prototype of such a system. The system operates at a relatively low frequency of 325 kHz (bandwidth 270-380 kHz) to accentuate mechanical effects and minimize the shift of the focal point, field distortion, and acoustic attenuation. We evaluated the transcranial performance of the system through 21 ex-vivo human skulls. There was a favorably low shift of the focal point (mean of 1.2 mm; 2.6 mm max), a minimal increase in focal volume (mean increase of 18%), and moderate attenuation of the pressure field (average 67% pressure attenuation). These values were achieved without phase correction. These results demonstrate that systems operating at a relatively low frequency are less prone to the aberrations of ultrasound by the skull, and provide a prototype that has the potential to be used for combined neuromodulation and mechanical therapies. However, translation to clinical high-intensity applications will require further validation, including in-vivo thermometry and safety testing.