Document Detail


Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo.
MedLine Citation:
PMID:  19846365     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The therapeutic efficacy of neurological agents is severely limited, because large compounds do not cross the blood-brain barrier (BBB). Focused ultrasound (FUS) sonication in the presence of microbubbles has been shown to temporarily open the BBB, allowing systemically administered agents into the brain. Until now, polydispersed microbubbles (1-10 microm in diameter) were used, and, therefore, the bubble sizes better suited for inducing the opening remain unknown. Here, the FUS-induced BBB opening dependence on microbubble size is investigated. Bubbles at 1-2 and 4-5 microm in diameter were separately size-isolated using differential centrifugation before being systemically administered in mice (n = 28). The BBB opening pressure threshold was identified by varying the peak-rarefactional pressure amplitude. BBB opening was determined by fluorescence enhancement due to systemically administered, fluorescent-tagged, 3-kDa dextran. The identified threshold fell between 0.30 and 0.46 MPa in the case of 1-2 microm bubbles and between 0.15 and 0.30 MPa in the 4-5 microm case. At every pressure studied, the fluorescence was greater with the 4-5 mum than with the 1-2 microm bubbles. At 0.61 MPa, in the 1-2 microm bubble case, the fluorescence amount and area were greater in the thalamus than in the hippocampus. In conclusion, it was determined that the FUS-induced BBB opening was dependent on both the size distribution in the injected microbubble volume and the brain region targeted.
Authors:
James J Choi; Jameel A Feshitan; Babak Baseri; Shougang Wang; Yao-Sheng Tung; Mark A Borden; Elisa E Konofagou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-10-20
Journal Detail:
Title:  IEEE transactions on bio-medical engineering     Volume:  57     ISSN:  1558-2531     ISO Abbreviation:  IEEE Trans Biomed Eng     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-12     Completed Date:  2010-03-30     Revised Date:  2014-05-25    
Medline Journal Info:
Nlm Unique ID:  0012737     Medline TA:  IEEE Trans Biomed Eng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  145-54     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier / ultrasonography*
Brain Chemistry
Drug Delivery Systems / methods*
Echoencephalography
Histocytochemistry
Male
Mice
Mice, Inbred C57BL
Microbubbles*
Microscopy, Fluorescence
Permeability
Ultrasonography / methods*
Grant Support
ID/Acronym/Agency:
R01 EB009041/EB/NIBIB NIH HHS; R01EB009041/EB/NIBIB NIH HHS; R21 EY018505/EY/NEI NIH HHS; R21EY018505/EY/NEI NIH HHS
Comments/Corrections

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