A prototype design of a low-frequency ultrasound phased-array system for blood-brain barrier (BBB) disruption (Focused ultrasound driving system for BBB disruption)

The purpose of this study was to demonstrate a prototype design of a low-frequency multiple-channel hemispherical focused-ultrasound phased-array system for transcranial disruption of the blood-brain barrier (BBB). In this study, we have presented a prototype design of a multiplechannel ultrasound hemispherical phased-array system to perform localized BBB disruption. To our knowledge this is the first phased-array system employing ultrasound at a frequency range suitable for transcranial sonication for BBB disruption. In our system design, the driving system includes a microcontroller/ field-programmable-gate-array (FPGA)-based control kernel with multiple-channel driving circuits implemented by a highvoltage switching/ LC-resonance/ impedance-matching circuit module. Three hemispherical phased arrays comprising 22, 31, 48, and 80 elements were fabricated and tested. The pressure distributions at the geometric center and at off-center positions were tested experimentally. The focal performance of the different hemispherical arrays was also evaluated theoretically. A 32-channel ultrasound driving system tunable in the frequency range from 200 to 400 kHz was designed for producing a suitable ultrasound output for BBB disruption. Results showed that the developed phased-array system can successfully drive the hemispherical array with multiple-channel ultrasound signals with independent phase control at 8-bit resolution. Preliminary animal experiments confirm its feasibility of disrupting the BBB through the intact animal skull. The described system could act as a platform design example or a reference for the development of a transcranial focused-ultrasound phased-array system for the clinical application of brain drug delivery.