Toward optimization of blood brain barrier opening induced by laser-activated perfluorocarbon nanodroplets

The blood brain barrier (BBB), a component of the brain's natural defense system, is often a roadblock for the monitoring and treatment of neurological disorders. Recently, we introduced a technique to open the blood brain barrier through the use of laser-activated perfluorohexane nanodroplets (PFHnDs), a phase-change nanoagent that undergoes repeated vaporization and recondensation when excited by a pulsed laser. Laser-activated PFHnDs were shown to enable noninvasive and localized opening of the BBB, allowing extravasation of various sized agents into the brain tissue. In this current work, the laser-activated PFHnD-induced BBB opening is further explored. In particular, laser fluence and the number of laser pulses used for the PFHnD-induced BBB opening are examined and evaluated both qualitatively and quantitatively to determine the effect of these parameters on BBB opening. The results of these studies show trends between increased laser fluence and an increased BBB opening as well as between an increased number of laser pulses and an increased BBB opening, however, with limitations on the extent of the BBB opening after a certain number of pulses. Overall, the results of these studies serve as a guideline to choosing suitable laser parameters for safe and effective BBB opening.