Fluorescence imaging of Evans blue extravasation into mouse brain induced by low frequency ultrasound with microbubble.

Blood-Brain Barrier (BBB) can be opened locally, noninvasively and reversibly by low frequency focused ultra-sound (FUS) in the presence of microbubbles. In this study, Evans blue (EB) dye extravasation across BBB was enhanced by 1 MHz FUS at acoustic pressure of 0.35 MPa in the presence of microbubbles at clinically comparable dosage. The spatial distribution of EB extravasation was visualized using fluorescence imaging method. The center region of BBB disruption area showed more enhanced fluorescence signal than the surrounding region in general. However, EB dye deposition was heterogeneous in the center region. The findings in this study indicated potential use of fluorescence imaging to evaluate large molecules delivery across BBB.