Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

摘要: Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) blood-brain barrier (BBB) in multiple vivo models including non-human primates (NHP). This procedure promise for clinical and basic science applications, yet safety potential neurological effects long term application NHP requires further investigation under parameters be efficacious species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened BBB caudate putamen regions basal ganglia 4 using FUS systemically-administered MB over 4–20 months. We assessed MRI detect edema or hemorrhaging brain. Contrast enhanced T1-weighted sequences showed 98% success rate openings targeted regions. T2-weighted SWI indicated lack majority cases. investigated through quantitative cognitive testing of’ visual, cognitive, motivational, motor function random dot motion task reward magnitude bias presented on touchpanel display. Reaction times during significantly increased day procedure. increase returned baseline within 4–5 days after Visual discrimination thresholds were unaffected. Our results indicate can safe method repeated opening at up 20 months without any long-term negative physiological used.