Dual-Mode Focused Ultrasound Array System for Controlled and Monitored Blood-Brain Barrier Opening

Focused ultrasound (FUS) combined the administration of microbubbles has been utilized for transient and noninvasive blood-brain barrier (BBB) opening, and become one of the most promising approach to delivery therapeutic agent into brain fore CNS disease therapy. The current one of the biggest bottleneck of FUS-facilitated CNS therapeutics delivery is the skull-inserted aberration and transcranial beam-steering capability, particularly for future clinical practice as the human skull thickness typically reaching 10-15 mm. In addition, to ensure the quality of the BBB opening, a feedback mechanism to control the exact ultrasound energy exposure in considering the of the skull bone heterogeneity for each individual. A possible solution is the use of ultrasound phased array system with the element been operated at dual transmit/ receive mode, so that the phase aberration can be corrected, to provide significant high geometrical gain to allow ultrasound energy focusing at the treatment target, and reversely to provide opportunity to receive significant high channel backscattered emissions for cavitation identification and mapping. In this research proposal, we aim to propose a full 256-channel dual transmit/ receive mode ultrasound phased array system, with the function to real-time control and monitor transcranial BBB opening process. In order to fulfill the real-time BBB-opening control based on the backscattered emission to overcome transcranial obstacles, the following technique gaps should be filled: (1) To implement a full 256-channel dual transmit/ receive mode phased array system structure in order to maximize the geometrical gain as well as maximize the backscattered emissions, (2) to implement a processing architecture to real-time perform multiple-channel backscattered emissions analysis, (3) to implement a real-time acoustic-emission based control scheme for BBB-opening, (4) to implement a real-time passive mapping to monitor the acoustic cavitation spatial distribution, and (5) to examine the feasibility of the BBB-opening control scheme to deliver therapeutics on PD animal models via the developed transcranial phased array, as well as verify the system via the large animal test. A three-year development is anticipated to fulfill the above mentioned tasks. The potential outcomes includes the scientific progress, key technology and IP production, as well as personnel training for medical device or biological industries.

Project ID:PB10901-2627
External Project ID:MOST108-2221-E182-017-MY3