Fig. 4.

Controlling model drug delivery across the BBB. (A) Schematic illustration of the experimental protocol. (B) The correlation between fluorescent intensity enhancement (Fluo. Enhance.) and the total HE. Data in red were acquired from sonications in the striatum and hippocampus with different sonication durations (60, 90, or 120 s; n = 7 for each duration). The calibrated delivery reference curve was then constructed by fitting a piecewise linear regression (dotted lines, 95% confidence intervals). Solid red dots represent cases whose fluorescent intensities were more than two SDs above the mean of those in the nonsonicated control group (n = 10 for each target); otherwise, data are shown as hollow red dots. Data marked in green show TB delivery in experiments where sonication was performed until total HE reached a preset goal: 1,500 dB (n = 4), 2,100 dB (n = 8), or 2,700 dB (n = 5). Error bars represent SEM. (C) Representative H&E-stained brain slices showing no vascular/neuronal damage. (Scale bar, 500 µm.)