Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics
Abstract Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a pos...
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| Veröffentlicht in: | Ultrasound in medicine & biology 2016-05, Vol.42 (5), p.1145-1166 |
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| creator | Healey, Andrew John Sontum, Per Christian Kvåle, Svein Eriksen, Morten Bendiksen, Ragnar Tornes, Audun Østensen, Jonny |
| description | Abstract Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers. |
| doi_str_mv | 10.1016/j.ultrasmedbio.2015.12.011 |
| format | Article |
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Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.</description><identifier>ISSN: 0301-5629</identifier><identifier>EISSN: 1879-291X</identifier><identifier>DOI: 10.1016/j.ultrasmedbio.2015.12.011</identifier><identifier>PMID: 26831341</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Acoustic cluster therapy ; Animals ; Blood Chemical Analysis ; Contrast Media - chemistry ; Contrast Media - radiation effects ; Delayed-Action Preparations ; Dogs ; Dose-Response Relationship, Radiation ; Droplet vaporization ; Ex vivo bubble sizing ; Ferric Compounds - blood ; Ferric Compounds - chemistry ; Ferric Compounds - radiation effects ; Gases - chemical synthesis ; Gases - radiation effects ; High-Energy Shock Waves ; In vitro bubble sizing ; In vivo bubble sizing ; Iron - blood ; Iron - chemistry ; Iron - radiation effects ; Male ; Microbubbles ; Myocardial perfusion imaging ; Oxides - blood ; Oxides - chemistry ; Oxides - radiation effects ; Particle Size ; Radiation Dosage ; Radiology ; Sonication - methods ; Ultrasound contrast agent</subject><ispartof>Ultrasound in medicine & biology, 2016-05, Vol.42 (5), p.1145-1166</ispartof><rights>World Federation for Ultrasound in Medicine & Biology</rights><rights>2016 World Federation for Ultrasound in Medicine & Biology</rights><rights>Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-96444fe5f87e905bfbf01955d5bfb7cf3a1e3a56eb7bae02cca1a11dc0b298a03</citedby><cites>FETCH-LOGICAL-c468t-96444fe5f87e905bfbf01955d5bfb7cf3a1e3a56eb7bae02cca1a11dc0b298a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0301562915007358$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26831341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Healey, Andrew John</creatorcontrib><creatorcontrib>Sontum, Per Christian</creatorcontrib><creatorcontrib>Kvåle, Svein</creatorcontrib><creatorcontrib>Eriksen, Morten</creatorcontrib><creatorcontrib>Bendiksen, Ragnar</creatorcontrib><creatorcontrib>Tornes, Audun</creatorcontrib><creatorcontrib>Østensen, Jonny</creatorcontrib><title>Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics</title><title>Ultrasound in medicine & biology</title><addtitle>Ultrasound Med Biol</addtitle><description>Abstract Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.</description><subject>Acoustic cluster therapy</subject><subject>Animals</subject><subject>Blood Chemical Analysis</subject><subject>Contrast Media - chemistry</subject><subject>Contrast Media - radiation effects</subject><subject>Delayed-Action Preparations</subject><subject>Dogs</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Droplet vaporization</subject><subject>Ex vivo bubble sizing</subject><subject>Ferric Compounds - blood</subject><subject>Ferric Compounds - chemistry</subject><subject>Ferric Compounds - radiation effects</subject><subject>Gases - chemical synthesis</subject><subject>Gases - radiation effects</subject><subject>High-Energy Shock Waves</subject><subject>In vitro bubble sizing</subject><subject>In vivo bubble sizing</subject><subject>Iron - blood</subject><subject>Iron - chemistry</subject><subject>Iron - radiation effects</subject><subject>Male</subject><subject>Microbubbles</subject><subject>Myocardial perfusion imaging</subject><subject>Oxides - blood</subject><subject>Oxides - chemistry</subject><subject>Oxides - radiation effects</subject><subject>Particle Size</subject><subject>Radiation Dosage</subject><subject>Radiology</subject><subject>Sonication - methods</subject><subject>Ultrasound contrast agent</subject><issn>0301-5629</issn><issn>1879-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9u1DAQxiMEokvhFZDFiUuCJ47zpwekZbeFSkUcuiBulu1MhJck3trOqsvT8Cx9Mhy2IMSpp7Hl3zcjz_clySugGVAo32yzqQ9O-gFbZWyWU-AZ5BkFeJQsoK6aNG_g6-NkQRmFlJd5c5I8835LKa1KVj1NTvKyZsAKWCS3S20nH4wmqz5WdGTzDZ3cHc7I5Xj384sJzhI5tuT8dr7tLfmI0k8OBxwDsR1Z6mD2MmBL3k1K9UiuzQ8ka-ODM2oKxo6_5RscdtbJnqwPoxyM9s-TJ53sPb64r6fJ54vzzepDevXp_eVqeZXqoqxD2pRFUXTIu7rChnLVqY5Cw3k7HyvdMQnIJC9RVUoizbWWIAFaTVXe1JKy0-T1se_O2ZsJfRCD8Rr7Xo4Yfy6gamhTMlrUD0Crila8qHlEz46odtZ7h53YOTNIdxBAxWyS2Ip_TRKzSQJyEU2K4pf3cyYVn_9K_7gSgfURwLiYvUEnvDY4amyNQx1Ea83D5rz9r43uzWi07L_jAf3WTm6MqxcgfBSI6zkuc1qAx6AwXrNfLlHCSQ</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Healey, Andrew John</creator><creator>Sontum, Per Christian</creator><creator>Kvåle, Svein</creator><creator>Eriksen, Morten</creator><creator>Bendiksen, Ragnar</creator><creator>Tornes, Audun</creator><creator>Østensen, Jonny</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20160501</creationdate><title>Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics</title><author>Healey, Andrew John ; Sontum, Per Christian ; Kvåle, Svein ; Eriksen, Morten ; Bendiksen, Ragnar ; Tornes, Audun ; Østensen, Jonny</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-96444fe5f87e905bfbf01955d5bfb7cf3a1e3a56eb7bae02cca1a11dc0b298a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acoustic cluster therapy</topic><topic>Animals</topic><topic>Blood Chemical Analysis</topic><topic>Contrast Media - chemistry</topic><topic>Contrast Media - radiation effects</topic><topic>Delayed-Action Preparations</topic><topic>Dogs</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Droplet vaporization</topic><topic>Ex vivo bubble sizing</topic><topic>Ferric Compounds - blood</topic><topic>Ferric Compounds - chemistry</topic><topic>Ferric Compounds - radiation effects</topic><topic>Gases - chemical synthesis</topic><topic>Gases - radiation effects</topic><topic>High-Energy Shock Waves</topic><topic>In vitro bubble sizing</topic><topic>In vivo bubble sizing</topic><topic>Iron - blood</topic><topic>Iron - chemistry</topic><topic>Iron - radiation effects</topic><topic>Male</topic><topic>Microbubbles</topic><topic>Myocardial perfusion imaging</topic><topic>Oxides - blood</topic><topic>Oxides - chemistry</topic><topic>Oxides - radiation effects</topic><topic>Particle Size</topic><topic>Radiation Dosage</topic><topic>Radiology</topic><topic>Sonication - methods</topic><topic>Ultrasound contrast agent</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Healey, Andrew John</creatorcontrib><creatorcontrib>Sontum, Per Christian</creatorcontrib><creatorcontrib>Kvåle, Svein</creatorcontrib><creatorcontrib>Eriksen, Morten</creatorcontrib><creatorcontrib>Bendiksen, Ragnar</creatorcontrib><creatorcontrib>Tornes, Audun</creatorcontrib><creatorcontrib>Østensen, Jonny</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Ultrasound in medicine & biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Healey, Andrew John</au><au>Sontum, Per Christian</au><au>Kvåle, Svein</au><au>Eriksen, Morten</au><au>Bendiksen, Ragnar</au><au>Tornes, Audun</au><au>Østensen, Jonny</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics</atitle><jtitle>Ultrasound in medicine & biology</jtitle><addtitle>Ultrasound Med Biol</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>42</volume><issue>5</issue><spage>1145</spage><epage>1166</epage><pages>1145-1166</pages><issn>0301-5629</issn><eissn>1879-291X</eissn><abstract>Abstract Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. 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| subjects | Acoustic cluster therapy Animals Blood Chemical Analysis Contrast Media - chemistry Contrast Media - radiation effects Delayed-Action Preparations Dogs Dose-Response Relationship, Radiation Droplet vaporization Ex vivo bubble sizing Ferric Compounds - blood Ferric Compounds - chemistry Ferric Compounds - radiation effects Gases - chemical synthesis Gases - radiation effects High-Energy Shock Waves In vitro bubble sizing In vivo bubble sizing Iron - blood Iron - chemistry Iron - radiation effects Male Microbubbles Myocardial perfusion imaging Oxides - blood Oxides - chemistry Oxides - radiation effects Particle Size Radiation Dosage Radiology Sonication - methods Ultrasound contrast agent |
| title | Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics |
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