Enhancement of direct brain infusion with focused ultrasound and microbubbles

Direct infusion to the brain is a frequently used technique in pre-clinical neuroscience research as well as several clinical applications. The relatively high intracranial pressure is one of the limiting factors that hinder efficient diffusion from the cannula tip. In this study, we utilized focused ultrasound (FUS) and microbubbles to condition the brain prior to performing the direct infusion. The acoustic parameters used for sonications were: 0.45 MPa peak rarefactional pressure, 6.7 ms pulse length, 5 Hz pulse repetition frequency, and a duration of 60 s. A 9.4 T magnetic resonance imaging (MRI) system was used to monitor the diffusion of an albumin-tagged MR contrast agent up to two hours. In addition, the diffusion of a commonly used gene therapy vector - adeno-associated virus (AAV) was evaluated via fluorescence imaging. Our results revealed that Pre-treatment with FUS and microbubbles significantly enhanced the total volume (P<;0.001) and volume increase (P<;0.05) of MR contrast agent in vivo.