Design Experimental Evaluation of a 256-Channel Dual-Frequency Ultrasound Phased-Array System for Transcranial Blood-Brain Barrier Opening Brain Drug Delivery
Journal
IEEE Transactions on Biomedical Engineering
Journal Volume
31
Journal Issue
4
Pages
1350-1360
Date Issued
2014
Author(s)
HL Liu
CK Jan
PC Chu
JC Hong
PY Lee
JD Hsu
CC Lin
CY Huang
PY Chen
KC Wei
HL Liu
CK Jan
PC Chu
JC Hong
PY Lee
JD Hsu
CC Lin
CY Huang
PY Chen
KC Wei
Abstract
Focused ultrasound (FUS) in the presence of microbubbles can bring about transcranial and local opening of the blood-brain barrier (BBB) for potential noninvasive delivery of drugs to the brain. A phased-array ultrasound system is essential for FUS-BBB opening to enable electronic steering and correction of the focal beam which is distorted by cranial bone. Here, we demonstrate our prototype design of a 256-channel ultrasound phased-array system for large-region transcranial BBB opening in the brains of large animals. One of the unique features of this system is the capability of generating concurrent dual-frequency ultrasound signals from the driving system for potential enhancement of BBB opening. A wide range of signal frequencies can be generated (frequency = 0.2-1.2 MHz) with controllable driving burst patterns. Precise output power can be controlled for individual channels via 8-bit duty-cycle control of transistor-transistor logic signals and the 8-bit microcontroller-controlled buck converter power supply output voltage. The prototype system was found to be in compliance with the electromagnetic compatibility standard. Moreover, large animal experiments confirmed the phase switching effectiveness of this system, and induction of either a precise spot or large region of BBB opening through fast focal-beam switching. We also demonstrated the capability of dual-frequency exposure to potentially enhance the BBB-opening effect. This study contributes to the design of ultrasound phased arrays for future clinical applications, and provides a new direction toward optimizing FUS brain drug delivery.
SDGs
Type
journal article