Bilateral-array focused ultrasound transducer with dual-frequency mode for blood-brain barrier opening in presence of microbubbles

In this study, we investigated the local bloodbrain barrier (BBB) opening produced by a bilateral two-element spherical ultrasound transducer with dual-frequency mode in presence of micro-bubbles (MB). Both diameter and radius of curvature for the ultrasound transducer are 10.0cm, and the driving frequency is 10kHz difference for the left and the right elements to generate an oscillatory-amplitude focal zone. The ultrasound sonication parameters are pulse length 10ms, duty cycle 1%, sonication duration 20s or 60s, and peak negative pressure 0.53 MPa, with different doses of MB. The ultrasound contrast agent (UCA), SonoVue, was used as the MB to enhance the BBB opening and Evans blue (EB) to evaluate the opening. The in vivo experimental results showed that this focused ultrasound transducer with dual-frequency mode can enlarge the BBB opening region as compared with the single-frequency mode. The results of this study indicated that dual-frequency focused ultrasound producing an oscillatory-amplitude focal zone is promising for opening a larger local BBB with less blood vessel damage.