MRI guided focused ultrasound opening of blood brain barrier

Abstract

Previously, we demonstrated that focused ultrasound can focally open the blood brain barrier (BBB) reversibly without damage to the neurons. In this study, we varied the ultrasound pulse parameters to investigate their influence on BBB opening and any resulting tissue damage. Under magnetic resonance imaging (MRI) guidance, a series of targeted ultrasound bursts (1.5 MHz, burst duration: 5 cycles to 100 ms, repetition frequency: 1 Hz–1 kHz) were delivered into rabbit brains at low pressure levels (up to approximately 5 MPa) after intravenous administration of a commercially available ultrasound contrast agent containing preformed gas bubbles. Focal MRI signal intensity changes were observed during the deposition of acoustic energy. BBB opening at the correct target was confirmed by detecting the localized uptake of an MRI contrast agent. In some animals Trypan Blue was injected intravenously after the sonications. The animals were sacrificed at time intervals ranging from 2 h to 7 days. Light and electron microscopy evaluation was performed. No neuronal damage was observed at the lowest power levels that produced BBB opening. No neuronal damage was observed at the lowest power levels that produced BBB opening. Correlation of focal MRI signal changes to the uptake of a large molecular size contrast agent was observed demonstrating the potential of image guided drug delivery.