Design of an Array Transducer for Localizing Microbubble Activity Through the Skull

Transcranial focused ultrasound is an important tool for opening the blood brain barrier (BBB), which is typically performed by focusing ultrasonic energy through the skull into regions that have been perfused with microbubbles (MB). When sonicated, these MB oscillate and temporarily disrupt the local BBB. The procedure can be monitored for effectiveness and safety by analyzing the spectral content of echoes, and by using multiple receivers, where the active MB’s position can be triangulated, allowing for the localization of the BBB opening. The monitoring and localization of MB has been performed in rodents but translating into larger animals is a major challenge due to attenuation at the skull. Here, we used acoustic simulations to design a multi-element transmit array with multiple receivers and characterized its ability to generate a focus through the non-human primate (NHP) skull and assessed its performance in localizing MB activity while varying number and spatial arrangement of receivers, optimizing the focal gain, focal spot size, and ability to localize a MB. The resultant transducer allows for the delivery of high pressure at brain-region sized targets and can localize MB signals.