Focused ultrasound microbubble destruction-mediated changes in blood-brain barrier permeability assessed by contrast-enhanced magnetic resonance imaging.

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.