Figure 1.

BBB opening induced by FUS/MB treatment. (A) Illustration of the experimental setup and the timeline of the sonication procedure. (B) The acoustic peak pressure profile of the focused ultrasound beam at its lateral focal plane (the lateral width at half maximum intensity: 5.0 mm). (C) Representative photomicrograph of MBs with a lipid shell and perfluoropropane core. Scale bar: 20 µm. (D) MB size distribution. MBs were polydispersed with diameters ranging from 0.4 µm to 8 µm. (E) The time-intensity curve of contrast-enhanced B-mode imaging of the brain after MB injection. The signal intensity gradually dropped to the half level about 7 min later and to the initial amplitude about 15 min later. (F) BBB opening area after a one-time FUS/MB treatment revealed by Evans blue (EB) extravasation (yellow dotted circle). Mice were unilaterally sonicated on the right hemisphere and the left hemisphere was used as the control. Left: treated by FUS only without MB injection. Right: treated by FUS/MB. The blue coloration could be visible only in the FUS/MB-treated site. The center of the target region was positioned 1.5-mm anterior to the lambda and 2.0-mm laterally towards the right hemisphere. Scale bar: 5 mm. (G) Fluorescence images of EB extravasated into the brain interstitium of the same brains in (F). Scale bar: 5 mm. (H) Scheme of treatment and behavioral tests in eight-month-old 3×Tg-AD mice receiving sham or FUS or FUS/MB treatment twice per week for a total duration of six weeks.