Global sonication of the human intracranial space via a jumbo planar transducer

Contrary to conditioning a Focused Ultrasound (FUS) beam to sonicate a localized region of the human brain, the goal of this investigation was to explore the prospect of distributing homogeneous ultrasound energy over the entire brain space with a large cranium-wide ultrasound beam. Recent ultrasound preclincal studies utilizing large or whole brain stimulation regions create a demand for expanding the treatment envelope of transcranial pulsed-low intensity ultrasound towards Global Brain Sonication (GBS) for potential human investigation. Here, we conduct ultrasound field characterizations when transmitting pulsed ultrasound through human skull specimens using a 1-3 piezocomposite planar transducer operating at 464 kHz with an active single-element surface of 30 × 30 cm. Through computational simulation and hydrophone scanning methodology, ultrasound wave behavior and dose homogeneity in the brain space were evaluated under various trajectories of sonication using the planar transducer. Clinically relevant pulse parameters used for transcranial therapeutic ultrasound applications were used in the experiments. Simulations and empirical testing revealed that dose homogeneity and acoustic intensity over the brain space are influenced by sonication trajectory, skull lens effects, and acoustic wave reflections. The transducer can emit a spatial peak pulse average intensity of 4.03 W/cm² (0.24 MPa) measured in the free-field at 464 kHz with electrical power of 1 kW. The simulation showed that approximately 99 % of the cranial volume was exposed with <30 % of the maximum external acoustic intensity being transmitted into the skull. The transmission loss across all sonication trajectories is similar to previously reported FUS studies. A marker for GBS dose homogeneity is introduced to score the ultrasound pressure field uniformity in the intracranial space. Results of this study identify the initial challenges of exposing the entire human brain space with ultrasound using a large cranium-wide sonication beam intended for global brain therapeutic modulation.