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dc.contributor.authorVlaisavljevich, Elien_US
dc.contributor.authorDurmaz, Yasemin Yukselen_US
dc.contributor.authorMaxwell, Adamen_US
dc.contributor.authorElSayed, Mohameden_US
dc.contributor.authorXu, Zhenen_US
dc.date.accessioned2017-11-14T21:00:00Z
dc.date.available2017-11-14T21:00:00Z
dc.date.issued2013-01-01en_US
dc.identifier.issn1838-7640en_US
dc.identifier.urihttp://hdl.handle.net/10919/80389
dc.description.abstractThis paper is an initial work towards developing an image-guided, targeted ultrasound ablation technique by combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. Using extremely short, high-pressure pulses, histotripsy generates a dense cloud of cavitating microbubbles that fractionates tissue. We hypothesize that synthetic nanodroplets that encapsulate a perfluoropentane (PFP) core will transition upon exposure to ultrasound pulses into gas microbubbles, which will rapidly expand and collapse resulting in disruption of cells similar to the histotripsy process but at a significantly lower acoustic pressure. The significantly reduced cavitation threshold will allow histotripsy to be selectively delivered to the tumor tissue and greatly enhance the treatment efficiency while sparing neighboring healthy tissue. To test our hypothesis, we prepared nanodroplets with an average diameter of 204±4.7 nm at 37°C by self-assembly of an amphiphilic triblock copolymer around a PFP core followed by cross-linkage of the polymer shell forming stable nanodroplets. The nanodroplets were embedded in agarose tissue phantoms containing a sheet of red blood cells (RBCs), which were exposed to 2-cycle pulses applied by a 500 kHz focused transducer. Using a high speed camera to monitor microbubble generation, the peak negative pressure threshold needed to generate bubbles >50 μm in agarose phantoms containing nanodroplets was measured to be 10.8 MPa, which is significantly lower than the 28.8 MPa observed using ultrasound pulses alone. High speed images also showed cavitation microbubbles produced from the nanodroplets displayed expansion and collapse similar to histotripsy alone at higher pressures. Nanodroplet-mediated histotripsy created consistent, well-defined fractionation of the RBCs in agarose tissue phantoms at 10 Hz pulse repetition frequency similar to the lesions generated by histotripsy alone but at a significantly lower pressure. These results support our hypothesis and demonstrate the potential of using nanodroplet-mediated histotripsy for targeted cell ablation.en_US
dc.format.extent851 - 864 (14) page(s)en_US
dc.languageEnglishen_US
dc.publisherIvyspring Int Publen_US
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000328162100004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en_US
dc.rightsCreative Commons Attribution NonCommercial NoDerivatives 3.0
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subjectHistotripsyen_US
dc.subjectnanodropletsen_US
dc.subjectcavitationen_US
dc.subjecttherapeutic ultrasounden_US
dc.subjecttargeted cell ablationen_US
dc.subjectACOUSTIC DROPLET VAPORIZATIONen_US
dc.subjectTISSUE EROSIONen_US
dc.subjectHIGH-INTENSITYen_US
dc.subjectTHERAPEUTIC ULTRASOUNDen_US
dc.subjectFOCUSED ULTRASOUNDen_US
dc.subjectSOFT-TISSUEen_US
dc.subjectCAVITATIONen_US
dc.subjectMODELen_US
dc.subjectMICELLESen_US
dc.subjectCREATIONen_US
dc.titleNanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablationen_US
dc.typeArticle - Refereed
dc.description.versionPublished (Publication status)en_US
dc.title.serialTHERANOSTICSen_US
dc.identifier.doihttps://doi.org/10.7150/thno.6717
dc.identifier.volume3en_US
dc.identifier.issue11en_US
pubs.organisational-group/Virginia Tech
pubs.organisational-group/Virginia Tech/All T&R Faculty
pubs.organisational-group/Virginia Tech/Engineering
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanics
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Faculty


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Creative Commons Attribution NonCommercial NoDerivatives 3.0
License: Creative Commons Attribution NonCommercial NoDerivatives 3.0