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Transcranial MRI-guided focused ultrasound is a rapidly advancing field for delivering therapeutic and imaging agents to the brain. It has the ability to facilitate the passage of therapeutics from the vasculature to the brain parenchyma, which is normally protected by the blood-brain barrier (BBB). Its main advantages are that it is targeted, noninvasive, and readily repeatable in nature. Studies have shown that it can deliver liposomal doxorubicin (DOX), a chemotherapy agent with promise for tumors in the central nervous system, into the brain across BBB. However, prior studies have suggested that this agent may be significantly neurotoxic, even at small concentrations. Here, we studied whether multiple sessions of DOX administered after FUS-induced BBB disruption (FUS-BBBD) caused adverse events in the normal brain. First, we used fluorometry to measure the doxorubicin concentrations in the brain after FUS-BBBD. Next, we performed three weekly sessions with FUS-BBBD ± DOX administration.

Multiple sessions of liposomal doxorubicin and focused ultrasound mediated blood-brain barrier disruption: safety study