| Noninvasive and localized blood-brain barrier disruption using focused ultrasound can be achieved at short pulse lengths and low pulse repetition frequencies. | |
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MedLine Citation:
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PMID: 20842160 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ultrasound methods in conjunction with microbubbles have been used for brain drug delivery, treatment of stroke, and imaging of cerebral blood flow. Despite advances in these areas, questions remain regarding the range of ultrasound parameters that disrupt the blood-brain barrier (BBB). In this study, several conditions were investigated to either enhance or reduce the likelihood of BBB disruption. Pulsed focused ultrasound (frequency: 1.5 MHz, pressure: 0.46 MPa, pulse repetition frequency (PRF): 0.1 to 25 Hz, pulse length (PL): 0.03 to 30 milliseconds) was noninvasively and locally administered to a predetermined region in the left hemisphere in the presence of circulating preformed microbubbles (Definity, Lantheus Medical Imaging, N. Billerica, MA, USA; 0.01, 0.05, 0.25 μL/g). Trans-BBB delivery of 3-kDa dextran was observed at PRFs as low as 1 Hz, whereas consistent delivery was observed at 5 Hz and above. Delivery was demonstrated at a PL as low as 33 microseconds. Although the delivered dextran concentration increased with the PL, this also increased the heterogeneity of the resulting distribution. In conclusion, key parameters that disrupt the BBB were identified out of a wide range of conditions. Reducing the total number of emitted acoustic cycles by shortening the PL, or decreasing the PRF, was also found to facilitate a more spatially uniform distribution of delivered dextran. |
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Authors:
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James J Choi; Kirsten Selert; Zimeng Gao; Gesthimani Samiotaki; Babak Baseri; Elisa E Konofagou |
Publication Detail:
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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: 2010-09-15 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 31 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-04 Completed Date: 2011-03-17 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 725-37 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, Columbia University, New York, New York 10027, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood-Aqueous Barrier / radiation effects* Chemistry, Pharmaceutical Dextrans / administration & dosage, pharmacokinetics Fluorescent Dyes / administration & dosage, pharmacokinetics Immunohistochemistry Male Mice Mice, Inbred C57BL Microscopy, Fluorescence Stereotaxic Techniques Time Factors Ultrasonics* |
| Grant Support | |
ID/Acronym/Agency:
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R01 EB 009041/EB/NIBIB NIH HHS; R21EY 018505/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fluorescent Dyes; 9004-54-0/Dextrans |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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