Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications

摘要: The purpose of this study was to test the hypothesis that burst ultrasound in presence an contrast agent can disrupt blood-brain barrier (BBB) with acoustic parameters suitable for completely noninvasive exposure through skull. 10-ms exposures were targeted brains 22 rabbits a frequency 690 kHz, repetition 1 Hz, and peak rarefactional pressure amplitudes up 3.1 MPa. total (sonication) time 20 s. Prior each sonication, bolus injected intravenously. Contrast-enhanced MR images obtained after sonications detect localized BBB disruption via local enhancement brain. Brain sections stained HE at 0.8 MPa, 90%; 1.4 100% sonicated locations showed enhancement. histology findings following 4 h survival indicated brain tissue necrosis induced approximately 70-80% amplitude level 2.3 MPa or higher. At lower amplitudes, however, small areas erythrocyte extravasation seen. electron microscopy demonstrated HRP passage vessel walls both transendothelial paraendothelial routes. These results demonstrate focal is possible.