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dc.contributor.authorRaymond, Scott Bruce
dc.contributor.authorTreat, Lisa H.
dc.contributor.authorDewey, Jonathan D.
dc.contributor.authorMcDannold, Nathan Judson
dc.contributor.authorHynynen, Kullervo
dc.contributor.authorBacskai, Brian
dc.date.accessioned2011-04-18T01:21:48Z
dc.date.issued2008
dc.identifier.citationRaymond, Scott B., Lisa H. Treat, Jonathan D. Dewey, Nathan J. McDannold, Kullervo Hynynen, and Brian J. Bacskai. 2008. Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models. PLoS ONE 3(5): e2175.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4853400
dc.description.abstractAlzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5±5.4-fold increase in Trypan blue fluorescence and 2.7±1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP), across a large age range (9–26 months), with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0002175en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364662/pdf/en_US
dash.licenseLAA
dc.subjectbiotechnologyen_US
dc.subjectbioengineeringen_US
dc.subjectneurological disordersen_US
dc.subjectAlzheimer diseaseen_US
dc.subjectradiology and medical imagingen_US
dc.subjectmagnetic resonance imagingen_US
dc.subjectultrasonographyen_US
dc.titleUltrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Modelsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorBacskai, Brian
dc.date.available2011-04-18T01:21:48Z
dash.affiliation.otherHMS^Radiology-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0002175*
dash.contributor.affiliatedRaymond, Scott
dash.contributor.affiliatedMcDannold, Nathan
dash.contributor.affiliatedBacskai, Brian


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