Effects of droplet composition on nanodroplet-mediated histotripsy

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dc.authorid0000-0003-2776-5807
dc.contributor.authorVlaisavljevich, Eli
dc.contributor.authorAydın, Ömer
dc.contributor.authorDurmaz Yüksel, Yasemin
dc.contributor.authorLin, Kuang-Wei
dc.contributor.authorFowlkes, Brian
dc.contributor.authorXu, Zhen
dc.contributor.authorElSayed, Mohamed E. H.
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:04:19Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:04:19Z
dc.date.issued2016
dc.departmentİstanbul Medipol Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomedikal Mühendisliği Bölümü
dc.descriptionWOS: 000373384700012
dc.descriptionPubMed ID: 26774470
dc.description.abstractNanodroplet-mediated histotripsy (NMH) is a targeted ablation technique combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. In two previous studies, polymer-encapsulated perfluoropentane nanodroplets were used to generate well-defined ablation similar to that obtained with histotripsy, but at significantly lower pressure, whenNMHtherapy was applied at a pulse repetition frequency (PRF) of 10 Hz. However, cavitation was not maintained over multiple pulses when ultrasound was applied at a lower PRF (i.e., 1-5 Hz). We hypothesized that nanodroplets with a higher-boiling-point perfluorocarbon core would provide sustainable cavitation nuclei, allowing cavitation to be maintained over multiple pulses, even at low PRF, which is needed for efficient and complete tissue fractionation via histotripsy. To test this hypothesis, we investigated the effects of droplet composition on NMH therapy by applying histotripsy at various frequencies (345 kHz, 500 kHz, 1.5 MHz, 3 MHz) to tissue phantoms containing perfluoropentane (PFP, boiling point similar to 29 degrees C, surface tension similar to 9.5 mN/m) and perfluorohexane (PFH, boiling point similar to 56 degrees C, surface tension similar to 11.9 mN/m) nanodroplets. First, the effects of droplet composition on the NMH cavitation threshold were investigated, with results revealing a significant decrease (>10 MPa) in the peak negative pressure (p-) cavitation threshold for both types of nanodroplets compared with controls. A slight decrease (similar to 1-3 MPa) in threshold was observed for PFP phantoms compared with PFH phantoms. Next, the ability of nanodroplets to function as sustainable cavitation nuclei over multiple pulses was investigated, with results revealing that PFH nanodroplets were sustainable cavitation nuclei over 1,000 pulses, whereas PFP nanodroplets were destroyed during the first few pulses (<50 pulses), likely because of the lower boiling point. Finally, tissue phantoms containing a layer of embedded red blood cells were used to compare the damage generated for NMH treatments using PFP and PFH droplets, with results indicating that PFH nanodroplets significantly improved NMH ablation, allowing for well-defined lesions to be generated at all frequencies and PRFs tested. Overall, the results of this study provide significant insight into the role of droplet composition in NMH therapy and provide a rational basis to tailor droplet parameters to improve NMH tissue fractionation.
dc.description.sponsorshipNational Science Foundation; Turkish Republic's Ministry of National Education Fellowship Program [1416]; U.S. Department of Defense [W81 XWH-11-PCRP-ID]en_US
dc.description.sponsorshipWe thank Sonja Capracotta (Technical Specialist, Nano Sight, School of Public Health, University of Michigan) for her help on NTA size and concentration measurements. This material is based on work supported by a National Science Foundation Graduate Research Fellowship to Eli Vlaisavljevich. Omer Aydin acknowledges the support of the Turkish Republic's Ministry of National Education Fellowship Program (1416). This work was supported by a grant from the U.S. Department of Defense (W81 XWH-11-PCRP-ID).en_US
dc.identifier.citationVlaisavljevich, E., Aydın, Ö., Durmaz Yüksel, Y., Lin, K. W., Fowlkes, B., Xu, Z. ... ElSayed, M. E. H. (2016). Effects of droplet composition on nanodroplet-mediated histotripsy. Ultrasound In Medicine And Biology, 42(4), 931-946. https://dx.doi.org/10.1016/j.ultrasmedbio.2015.11.027
dc.identifier.doi10.1016/j.ultrasmedbio.2015.11.027
dc.identifier.endpage946
dc.identifier.issn0301-5629
dc.identifier.issn1879-291X
dc.identifier.issue4
dc.identifier.scopusqualityQ1
dc.identifier.startpage931
dc.identifier.urihttps://dx.doi.org/10.1016/j.ultrasmedbio.2015.11.027
dc.identifier.urihttps://hdl.handle.net/20.500.12511/4030
dc.identifier.volume42
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Science Inc
dc.relation.ispartofUltrasound In Medicine And Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectNanodroplet
dc.subjectHistotripsy
dc.subjectPerfluoropentane
dc.subjectPerfluorohexane
dc.subjectCavitation
dc.titleEffects of droplet composition on nanodroplet-mediated histotripsy
dc.typeArticle

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