Opening Of Blood-brain Barrier By Focused Ultrasound Combined With Microbubbles Or Hyperosmolar Solutions Of Mannitol In Rats

ObjectiveTo investigate the differences between focused ultrasound combinedwith microbubbles and hyperosmolar solutions of mannitol in opening theblood-brain barrier(BBB) in rats.MethodsA total of115SD rats were randomly divided into focused ultrasoundcombined with microbubbles group(A,n=50),mannitol group(B,n=50) andsaline group(C,n=15).The rats of group A were sonicated by focusedultrasound (1.9MHz、3.3W)for40seconds after microrbubbles(0.03ml/kg、(1～5)×108个/ml) injected through femoral vein,and those from groupB were infused internal carotid solutions of25%mannitol at0.12ml/s for30seconds,those of group C received0.9%saline injection throughfemoral vein. The changes in blood-brain barrier permeability wereassessed by contrast-enhanced magnetic resonance imaging(MRI), Exudation of Evans blue and fluorescent-tagged dextrans at two distinctmolecular weights were observed with fluorescence microscopy andfluorescencespectrometer.Results1. The MRI showed local BBB opening in rats from focusedultrasound combined with microbubbles group,while widespread frommannitol group.2. The signal intensity enhancements of focused ultrasound combinedwith microbubbles group were overall higher than those of mannitol groupat o,5,15,and30minutes(P<0.01and P<0.05).The amounts peaked at0minand significantly decreased at45minutes in focused ultrasound combinedwith microbubbles group,but5minutes and30minutes in mannitol group.3. Compared with the mannitol group,there were higher fluorescenceintensity of Evans blue and fluorescent-tagged dextrans in brain tissue fromfocused ultrasound combined with microbubbles group.Fluorescencedistribution of10kDa dextran is more homogeneous and dense than that of40kDa dextran.4. The content of Evans blue and fluorescent-tagged dextrans in braintissue from focused ultrasound combined with microbubbles group wasmarkedly greater than that from mannitol group (P<0.01).The10kDadextran extravasation was significantly higher than40kDa dextranextravasation in both the two study groups(P<0.01). ConclusionAs compared to mannitol infusion, focused ultrasound combined withmicrobubbles is a metheod of noinvasive,selective and localized openingBBB.