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Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos
Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology...
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Published in: | Angiogenesis (London) 2015-01, Vol.18 (1), p.69-81 |
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container_title | Angiogenesis (London) |
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creator | Denbeigh, J. M. Nixon, B. A. Lee, J. J. Y. Jerkic, M. Marsden, P. A. Letarte, M. Puri, M. C. Foster, F. S. |
description | Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology and detecting individual response to treatment. The objective of this study was to evaluate whether targeted ultrasound contrast-enhanced imaging can provide a quantitative measure of endogenous biomarkers. Endoglin, an endothelial biomarker involved in the processes of development, vascular homeostasis, and altered in diseases, including hereditary hemorrhagic telangiectasia type 1 and tumor angiogenesis, was the selected target. We used a parallel plate perfusion chamber in which endoglin-targeted (MB
E
), rat isotype IgG
2
control and untargeted microbubbles were perfused across endoglin wild-type (
Eng
+/+
), heterozygous (
Eng
+/−
) and null (
Eng
−/−
) embryonic mouse endothelial cells and their adhesion quantified. Microbubble binding was also assessed in late-gestation, isolated living transgenic
Eng
+/−
and
Eng
+/+
embryos. Nonlinear contrast-specific ultrasound imaging performed at 21 MHz was used to collect contrast mean power ratios for all bubble types. Statistically significant differences in microbubble binding were found across genotypes for both in vitro (
p
|
doi_str_mv | 10.1007/s10456-014-9447-0 |
format | article |
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E
), rat isotype IgG
2
control and untargeted microbubbles were perfused across endoglin wild-type (
Eng
+/+
), heterozygous (
Eng
+/−
) and null (
Eng
−/−
) embryonic mouse endothelial cells and their adhesion quantified. Microbubble binding was also assessed in late-gestation, isolated living transgenic
Eng
+/−
and
Eng
+/+
embryos. Nonlinear contrast-specific ultrasound imaging performed at 21 MHz was used to collect contrast mean power ratios for all bubble types. Statistically significant differences in microbubble binding were found across genotypes for both in vitro (
p
< 0.05) and embryonic studies (
p
< 0.001); MB
E
binding was approximately twofold higher in
Eng
+/+
cells and embryos compared with their
Eng
+/−
counterparts. These results suggest that molecular ultrasound is capable of reliably differentiating between molecular genotypes and relating receptor densities to quantifiable molecular ultrasound levels.</description><identifier>ISSN: 0969-6970</identifier><identifier>EISSN: 1573-7209</identifier><identifier>DOI: 10.1007/s10456-014-9447-0</identifier><identifier>PMID: 25298070</identifier><identifier>CODEN: AGIOFT</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Blotting, Western ; Cancer Research ; Cardiology ; Cell Adhesion - physiology ; Cell Biology ; Embryo, Mammalian - diagnostic imaging ; Endoglin ; Endothelial Cells - diagnostic imaging ; Endothelial Cells - physiology ; Genotype ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - physiology ; Lymphocytes, Null ; Mice ; Mice, Knockout ; Microbubbles ; Molecular Imaging ; Oncology ; Ophthalmology ; Original Paper ; Rats ; Ultrasonography</subject><ispartof>Angiogenesis (London), 2015-01, Vol.18 (1), p.69-81</ispartof><rights>Crown Copyright 2014</rights><rights>Springer Science+Business Media Dordrecht 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-202496b15bb228982453e8b077f6eed9fc602a607779b192979a181a004b63743</citedby><cites>FETCH-LOGICAL-c475t-202496b15bb228982453e8b077f6eed9fc602a607779b192979a181a004b63743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25298070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Denbeigh, J. M.</creatorcontrib><creatorcontrib>Nixon, B. A.</creatorcontrib><creatorcontrib>Lee, J. J. Y.</creatorcontrib><creatorcontrib>Jerkic, M.</creatorcontrib><creatorcontrib>Marsden, P. A.</creatorcontrib><creatorcontrib>Letarte, M.</creatorcontrib><creatorcontrib>Puri, M. C.</creatorcontrib><creatorcontrib>Foster, F. S.</creatorcontrib><title>Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos</title><title>Angiogenesis (London)</title><addtitle>Angiogenesis</addtitle><addtitle>Angiogenesis</addtitle><description>Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology and detecting individual response to treatment. The objective of this study was to evaluate whether targeted ultrasound contrast-enhanced imaging can provide a quantitative measure of endogenous biomarkers. Endoglin, an endothelial biomarker involved in the processes of development, vascular homeostasis, and altered in diseases, including hereditary hemorrhagic telangiectasia type 1 and tumor angiogenesis, was the selected target. We used a parallel plate perfusion chamber in which endoglin-targeted (MB
E
), rat isotype IgG
2
control and untargeted microbubbles were perfused across endoglin wild-type (
Eng
+/+
), heterozygous (
Eng
+/−
) and null (
Eng
−/−
) embryonic mouse endothelial cells and their adhesion quantified. Microbubble binding was also assessed in late-gestation, isolated living transgenic
Eng
+/−
and
Eng
+/+
embryos. Nonlinear contrast-specific ultrasound imaging performed at 21 MHz was used to collect contrast mean power ratios for all bubble types. Statistically significant differences in microbubble binding were found across genotypes for both in vitro (
p
< 0.05) and embryonic studies (
p
< 0.001); MB
E
binding was approximately twofold higher in
Eng
+/+
cells and embryos compared with their
Eng
+/−
counterparts. These results suggest that molecular ultrasound is capable of reliably differentiating between molecular genotypes and relating receptor densities to quantifiable molecular ultrasound levels.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blotting, Western</subject><subject>Cancer Research</subject><subject>Cardiology</subject><subject>Cell Adhesion - physiology</subject><subject>Cell Biology</subject><subject>Embryo, Mammalian - diagnostic imaging</subject><subject>Endoglin</subject><subject>Endothelial Cells - diagnostic imaging</subject><subject>Endothelial Cells - physiology</subject><subject>Genotype</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - physiology</subject><subject>Lymphocytes, Null</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microbubbles</subject><subject>Molecular Imaging</subject><subject>Oncology</subject><subject>Ophthalmology</subject><subject>Original Paper</subject><subject>Rats</subject><subject>Ultrasonography</subject><issn>0969-6970</issn><issn>1573-7209</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFkU1r3DAQhkVJyW4-fkAvxZBLL2pHsixZx7AkbWAhl_aQk5Dt8caLLW0k-7D_PjLehhIIPYmZeeaVxEPIFwbfGYD6ERmIQlJggmohFIVPZM0KlVPFQZ-RNWipqdQKVuQixj1AapTinKx4wXUJCtbkaePdGGwcKbpn62psssH3WE-9DdnUzyM_uSZrurbFgG7s7IgxQ9f4Xd-5bIfOj8dDaqVi8FPEDIcqHH28Ip9b20e8Pp2X5M_93e_NL7p9_Pmwud3SWqhipBy40LJiRVVxXuqSiyLHsgKlWonY6LaWwK1MtdIV01wrbVnJLICoZK5Efkm-LbmH4F8mjKMZulhj31uH6T2GKdBMcc3Y_1EpmOBFkc_ozTt076fg0kdmCrRSkkOi2ELVwccYsDWH0A02HA0DMysyiyKTFJlZkZl3vp6Sp2rA5m3jr5ME8AWIaeR2GP65-sPUV8aRmrw</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Denbeigh, J. M.</creator><creator>Nixon, B. A.</creator><creator>Lee, J. J. Y.</creator><creator>Jerkic, M.</creator><creator>Marsden, P. A.</creator><creator>Letarte, M.</creator><creator>Puri, M. C.</creator><creator>Foster, F. S.</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>3V.</scope><scope>7QO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20150101</creationdate><title>Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos</title><author>Denbeigh, J. M. ; Nixon, B. A. ; Lee, J. J. Y. ; Jerkic, M. ; Marsden, P. A. ; Letarte, M. ; Puri, M. C. ; Foster, F. S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-202496b15bb228982453e8b077f6eed9fc602a607779b192979a181a004b63743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blotting, Western</topic><topic>Cancer Research</topic><topic>Cardiology</topic><topic>Cell Adhesion - physiology</topic><topic>Cell Biology</topic><topic>Embryo, Mammalian - diagnostic imaging</topic><topic>Endoglin</topic><topic>Endothelial Cells - diagnostic imaging</topic><topic>Endothelial Cells - physiology</topic><topic>Genotype</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - physiology</topic><topic>Lymphocytes, Null</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microbubbles</topic><topic>Molecular Imaging</topic><topic>Oncology</topic><topic>Ophthalmology</topic><topic>Original Paper</topic><topic>Rats</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Denbeigh, J. M.</creatorcontrib><creatorcontrib>Nixon, B. A.</creatorcontrib><creatorcontrib>Lee, J. J. Y.</creatorcontrib><creatorcontrib>Jerkic, M.</creatorcontrib><creatorcontrib>Marsden, P. A.</creatorcontrib><creatorcontrib>Letarte, M.</creatorcontrib><creatorcontrib>Puri, M. C.</creatorcontrib><creatorcontrib>Foster, F. S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Angiogenesis (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Denbeigh, J. M.</au><au>Nixon, B. A.</au><au>Lee, J. J. Y.</au><au>Jerkic, M.</au><au>Marsden, P. A.</au><au>Letarte, M.</au><au>Puri, M. C.</au><au>Foster, F. S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos</atitle><jtitle>Angiogenesis (London)</jtitle><stitle>Angiogenesis</stitle><addtitle>Angiogenesis</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>18</volume><issue>1</issue><spage>69</spage><epage>81</epage><pages>69-81</pages><issn>0969-6970</issn><eissn>1573-7209</eissn><coden>AGIOFT</coden><abstract>Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology and detecting individual response to treatment. The objective of this study was to evaluate whether targeted ultrasound contrast-enhanced imaging can provide a quantitative measure of endogenous biomarkers. Endoglin, an endothelial biomarker involved in the processes of development, vascular homeostasis, and altered in diseases, including hereditary hemorrhagic telangiectasia type 1 and tumor angiogenesis, was the selected target. We used a parallel plate perfusion chamber in which endoglin-targeted (MB
E
), rat isotype IgG
2
control and untargeted microbubbles were perfused across endoglin wild-type (
Eng
+/+
), heterozygous (
Eng
+/−
) and null (
Eng
−/−
) embryonic mouse endothelial cells and their adhesion quantified. Microbubble binding was also assessed in late-gestation, isolated living transgenic
Eng
+/−
and
Eng
+/+
embryos. Nonlinear contrast-specific ultrasound imaging performed at 21 MHz was used to collect contrast mean power ratios for all bubble types. Statistically significant differences in microbubble binding were found across genotypes for both in vitro (
p
< 0.05) and embryonic studies (
p
< 0.001); MB
E
binding was approximately twofold higher in
Eng
+/+
cells and embryos compared with their
Eng
+/−
counterparts. These results suggest that molecular ultrasound is capable of reliably differentiating between molecular genotypes and relating receptor densities to quantifiable molecular ultrasound levels.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>25298070</pmid><doi>10.1007/s10456-014-9447-0</doi><tpages>13</tpages></addata></record> |
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subjects | Animals Biomedical and Life Sciences Biomedicine Blotting, Western Cancer Research Cardiology Cell Adhesion - physiology Cell Biology Embryo, Mammalian - diagnostic imaging Endoglin Endothelial Cells - diagnostic imaging Endothelial Cells - physiology Genotype Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - physiology Lymphocytes, Null Mice Mice, Knockout Microbubbles Molecular Imaging Oncology Ophthalmology Original Paper Rats Ultrasonography |
title | Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos |
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