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© 2009 by the American Institute of Ultrasound in Medicine
J Ultrasound Med 28:1501-1509 • 0278-4297

Focused Ultrasound Microbubble Destruction-Mediated Changes in Blood-Brain Barrier Permeability Assessed by Contrast-Enhanced Magnetic Resonance Imaging

Feng Wang, MS, Yuan Cheng, MD, Jie Mei, MS, Yu Song, PhD, Yan-qing Yang, MS, Yingjiang Liu, BRad and Zhibiao Wang, MD

Institute of Ultrasound Engineering in Medicine (F.W., Y.L., Z.W.) and Department of Neurosurgery, Second Affiliated Hospital (F.W., Y.C., J.M., Y.S., Y.Y.), Chongqing Medical University, Chongqing, China.

Address correspondence to Yuan Cheng, MD, Department of Neurosurgery, Second Affiliated Hospital, Chongqing Medical University, 74 Linjiang Rd, 400010 Yuzhong, Chongqing, China. E-mail: chengyuan023{at}yahoo.com.cn

Objective. The purpose of this study was to use enhanced magnetic resonance imaging (MRI) to evaluate the changes of blood-brain barrier (BBB) permeability in target and nontarget areas of rabbit brains after BBB disruption induced by focused ultrasound-mediated microbubble destruction. Methods. Focused ultrasound (1.1 MHz) in combination with a sulfur hexafluoride microbubble contrast agent was applied at 2 or 3 target locations in 1 hemisphere of 29 rabbit brains to induce BBB disruption. The opposite side was used as a control, and a normal group contained another 14 rabbits that did not undergo sonication. The MRI signal intensity enhancement in the target locations was detected to evaluate gadolinium (Ga) retention after sonication, and extravasation of Evans blue (EB) dye was detected to evaluate the BBB disruption quantitatively at different times after sonication (0.5, 2, 4, 6, 8, and 24 hours and 1 week). Results. Compared with the control group, Ga retention, changes in EB content, and extravasation in the cerebral cortex of the sonicated group peaked at 2 hours (P < .01) and decreased to the normal level 8 hours after sonication (P < .01). There was no visual evidence of injury or hemorrhage within the brain parenchyma of all of the rabbits’ treated hemispheres. Conclusions. Magnetic resonance imaging–guided focused ultrasound can disrupt the BBB reversibly and can allow targeted delivery of some molecules that normally cannot cross the BBB to locations in the brain. Changes in BBB permeability develop within minutes after sonication as a result of a combination of factors. The BBB has a self-repairing characteristic, which is activated after ultrasound sonication. This may offer an improvement in future clinical applications for central nervous system diseases.

Key Words: blood-brain barrier • cerebral vessel permeability • focused ultrasound • microbubble

Abbreviations: BBB, blood-brain barrier • EB, Evans blue • Ga, gadolinium • MRI, magnetic resonance imaging • ROI, region of interest

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Copyright © 2009 by the American Institute of Ultrasound in Medicine.