Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation

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dc.contributor.authorVlaisavljevich, Elien
dc.contributor.authorDurmaz, Yasemin Yukselen
dc.contributor.authorMaxwell, Adamen
dc.contributor.authorElSayed, Mohameden
dc.contributor.authorXu, Zhenen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessioned2017-11-14T21:00:00Zen
dc.date.available2017-11-14T21:00:00Zen
dc.date.issued2013-01-01en
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
dc.description.versionPublished versionen
dc.format.extent851 - 864 (14) page(s)en
dc.identifier.doihttps://doi.org/10.7150/thno.6717en
dc.identifier.issn1838-7640en
dc.identifier.issue11en
dc.identifier.urihttp://hdl.handle.net/10919/80389en
dc.identifier.volume3en
dc.languageEnglishen
dc.publisherIvyspring Int Publen
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
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectHistotripsyen
dc.subjectnanodropletsen
dc.subjectcavitationen
dc.subjecttherapeutic ultrasounden
dc.subjecttargeted cell ablationen
dc.subjectACOUSTIC DROPLET VAPORIZATIONen
dc.subjectTISSUE EROSIONen
dc.subjectHIGH-INTENSITYen
dc.subjectTHERAPEUTIC ULTRASOUNDen
dc.subjectFOCUSED ULTRASOUNDen
dc.subjectSOFT-TISSUEen
dc.subjectCAVITATIONen
dc.subjectMODELen
dc.subjectMICELLESen
dc.subjectCREATIONen
dc.titleNanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablationen
dc.title.serialTheranosticsen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanicsen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen

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