Transcranial MRI-guided focused ultrasound-induced blood-brain barrier opening in rats

Abstract

The use of cavitation-enhanced MRI-guided focused ultrasound (FUS) to disrupt the blood-brain barrier (BBB) locally and enhance drug delivery to the brain was investigated in rats with an intact skull. Contrast-enhanced MR images of 50 rat brains exposed in multiple locations to FUS in the presence of microbubbles were analyzed to determine the minimum focal pressure amplitude needed to achieve BBB opening, The images indicated that localized BBB opening was consistently achieved by applying FUS at estimated peak focal pressure amplitudes of 1.2 MPa or greater. In addition, the uptake of liposome-encapsulated doxorubicin in the brain tissue of six rats with and without exposure to FUS was quantified by fluorometry. Preliminary results indicated that FUS-enhanced drug delivery increased the uptake of liposomal doxorubicin by 53% compared to unexposed tissue. The successful delivery of molecules as large as 100 nm in diameter across the BBB indicates the clinical potential of FUS-enhanced drug delivery in the treatment of brain tumors.