Ultrasound-mediated delivery of gadolinium and fluorescent-labeled liposomes through the blood-brain barrier

The main objective of this study was to examine liposome extravasationacross the BBB as a function of size after disruption via ultrasound and microbubbles. The liposomes were labeled with gadolinium(Gd) and fluorophore, thus enabling detection of extravasatedliposomes via MRI in vivo and fluorescence methods in tissue, respectively. Liposomes labeled with gadoliniumand fluorophorewere prepared using lipid film hydration and extrusion to two different sizes (~80 nm and ~140 nm). Animals were divided into two groups based on the use of particle sizes. FUS–BBB disruption was produced in one hemisphere in 10 mice. Particles were injected before sonication. Sonications(0.69 MHz at 0.68 MPa) were performed in two locations combine with Definity (10 μl/kg). Acoustic emissions were recorded during FUS. T1 & T2*-weighted MRI were used to confirm Gd leakage and damage detection respectively. Mice were euthanized 5–24 h after FUS and post-process for fluorescence measurement. In sonicatedarea, Gd-leakage was...