The Effects of Oxygen on Ultrasound-Induced Blood–Brain Barrier Disruption in Mice

Abstract Numerous researchers are investigating the use of microbubble-enhanced ultrasound to disrupt the blood–brain barrier (BBB) and deliver drugs to the brain. This study investigated the impact of using oxygen as a carrier gas for anesthesia on microbubbleactivity and BBB disruption. Targets in mice were sonicatedin combination with administration of Optison microbubbles(100 μL/kg) under isofluraneanesthesia with either oxygen or medical air. A 690-kHz focused ultrasound transducer applied 10-ms bursts at peak pressure amplitudes of 0.46–0.54 MPa ( n = 2) or 0.34–0.36 MPa ( n = 5). After sonicationof two locations in one hemisphere, the carrier gas for the anesthesia was changed and the sonicationswere repeated in the contralateral hemisphere. The BBB disruption, measured via contrast-enhanced magnetic resonance imaging, was significantly greater ( p p 2 , 0.46) was observed between the harmonic emissions strength and magnetic resonance imaging signal enhancement. At 0.46–0.54 MPa, both the occurrence and strength of wideband emissions were greater with medical air. However, at lower peak pressure amplitudes of 0.34–0.36 MPa, the strength and probability for wideband emissions were higher with oxygen. Little or no effects were observed in histology at 0.34–0.36 MPa. These findings show that use of oxygen as a carrier gas can result in a substantial diminution of BBB disruption. These results should be taken into account when comparing studies from different researchers and in translating this method to humans.