P0-3 Focused Ultrasound-Induced Molecular Delivery through the Blood-Brain Barrier

The delivery of gadolinium through the ultrasound- induced blood-brain barrier (BBB) openings of mice was investigated. The left hippocampus of mice (n=13) was sonicated (frequency: 1.525 MHz, pressure amplitude: 0.64 MPa, duty cycle: 20%, duration: 1 minute) in vivo through the intact skin and skull after the injection of pre-formed microbubbles (SonoVuereg; 25-30 mul). The BBB opening in mice was studied using MRI (p=3) and fluorescent microscopy (q=10). High- resolution MRI (9.4 Tesla, in-plane resolution: 75 times 84 mum, scan time: 110 min) were acquired 60-90 min post-sonication before and after intraperitoneally injection of gadolinium (Omniscantrade; 0.75 ml, molecular weight: 573.7 Da). Four to ten minutes post- sonication, fluorescent dextran of various molecular weights (3,000, 70,000, and 2,000,000 Da) were delivered intravenously. MRI revealed contrast-enhancement and dextran revealed fluorescence following BBB opening. The gadolinium and dextran were nonuniformly distributed within the sonicated region. More specifically, contrast enhancement and fluorescence was more pronounced at different regions. The MRI procedure was repeated one day after opening and revealed BBB closure in the hippocampal region. In conclusion, gadolinium was deposited through the transiently opened BBB in the left hippocampus of mice using a single-element FUS transducer. The BBB opening and closing behaviors, and the size of BBB opening were dependent on the region sonicated. Molecules of smaller molecular weight were more uniformly deposited throughout the hippocampus than larger molecules.