Figure 4.
Blood–brain barrier (BBB) closure dynamics after ultrasound-induced disruption for magnetic resonance contrast agent (MR-CA) of different molecular sizes. Paramagnetic CA were injected at different times (0 to 24 hours) after BBB disruption. (A) Concentrations of the three paramagnetic CA in the region of interest in the cheek muscles CROImuscle were measured. (B) Index of delivered acoustic pressure at the ultrasound focal point in the right thalamus in the brain. The maximum variability within each group (CA) for these two parameters was 13%. (C) Corrected concentration (C*) of the CA at the ultrasound focal point in the brain was plotted as a function of the time elapsed between ultrasound-induced BBB opening and the MR-CA injection (n=1 rat per time point). All experimental data (n=28 rats) were used to fit the theoretical BBB closure model and determine the two parameters (σ0=1.54 nm, k=1.54 × 10−5 per second) (equation (6)); dashed lines correspond to the fitted data for each MR-CA. ROI, region of interest.