Molecular Imaging of the Initial Inflammatory Response in Atherosclerosis: Implications for Early Detection of Disease
BACKGROUND—We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could noninvasively evaluate prelesion atherogenic phenotype. METHODS AND RESULTS—Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2010-01, Vol.30 (1), p.54-59 |
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| container_title | Arteriosclerosis, thrombosis, and vascular biology |
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| creator | Kaufmann, Beat A Carr, Chad L Belcik, J Todd Xie, Aris Yue, Qi Chadderdon, Scott Caplan, Evan S Khangura, Jaspreet Bullens, Sherry Bunting, Stuart Lindner, Jonathan R |
| description | BACKGROUND—We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could noninvasively evaluate prelesion atherogenic phenotype.
METHODS AND RESULTS—Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultrahigh frequency ultrasound, histology, and immunohistochemistry. In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement (P |
| doi_str_mv | 10.1161/ATVBAHA.109.196386 |
| format | Article |
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METHODS AND RESULTS—Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultrahigh frequency ultrasound, histology, and immunohistochemistry. In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement (P<0.01 versus nontargeted agent) at all ages for DKO mice. P-selectin and VCAM-1 signal in DKO mice were greater by 3-fold at 10 weeks, 4- to 6-fold at 20 weeks, and 9- to 10-fold at 40 weeks compared to wild-type mice. En face microscopy demonstrated preferential attachment of targeted microbubbles to regions of lesion formation.
CONCLUSIONS—Noninvasive ultrasound molecular imaging of endothelial activation can detect lesion-prone vascular phenotype before the appearance of obstructive atherosclerotic lesions.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.109.196386</identifier><identifier>PMID: 19834105</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Animals ; Aorta, Thoracic - diagnostic imaging ; Aorta, Thoracic - immunology ; Aorta, Thoracic - metabolism ; Atherosclerosis (general aspects, experimental research) ; Atherosclerosis - diagnostic imaging ; Atherosclerosis - immunology ; Atherosclerosis - metabolism ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Flow Velocity ; Blood. Blood coagulation. Reticuloendothelial system ; Cardiology. Vascular system ; Cell Adhesion - immunology ; Disease Models, Animal ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Early Diagnosis ; Echocardiography ; Endothelial Cells - diagnostic imaging ; Endothelial Cells - immunology ; Endothelial Cells - metabolism ; Heterogeneous-Nuclear Ribonucleoproteins - genetics ; Immunohistochemistry ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; P-Selectin - metabolism ; Pharmacology. Drug treatments ; Phenotype ; Receptors, LDL - genetics ; Vascular Cell Adhesion Molecule-1 - metabolism</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2010-01, Vol.30 (1), p.54-59</ispartof><rights>2010 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4150-d99bca5a0deda13fd05c6b19602686271355fbb31d4f9730f901c8db0a57d3853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22338292$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19834105$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaufmann, Beat A</creatorcontrib><creatorcontrib>Carr, Chad L</creatorcontrib><creatorcontrib>Belcik, J Todd</creatorcontrib><creatorcontrib>Xie, Aris</creatorcontrib><creatorcontrib>Yue, Qi</creatorcontrib><creatorcontrib>Chadderdon, Scott</creatorcontrib><creatorcontrib>Caplan, Evan S</creatorcontrib><creatorcontrib>Khangura, Jaspreet</creatorcontrib><creatorcontrib>Bullens, Sherry</creatorcontrib><creatorcontrib>Bunting, Stuart</creatorcontrib><creatorcontrib>Lindner, Jonathan R</creatorcontrib><title>Molecular Imaging of the Initial Inflammatory Response in Atherosclerosis: Implications for Early Detection of Disease</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>BACKGROUND—We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could noninvasively evaluate prelesion atherogenic phenotype.
METHODS AND RESULTS—Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultrahigh frequency ultrasound, histology, and immunohistochemistry. In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement (P<0.01 versus nontargeted agent) at all ages for DKO mice. P-selectin and VCAM-1 signal in DKO mice were greater by 3-fold at 10 weeks, 4- to 6-fold at 20 weeks, and 9- to 10-fold at 40 weeks compared to wild-type mice. En face microscopy demonstrated preferential attachment of targeted microbubbles to regions of lesion formation.
CONCLUSIONS—Noninvasive ultrasound molecular imaging of endothelial activation can detect lesion-prone vascular phenotype before the appearance of obstructive atherosclerotic lesions.</description><subject>Animals</subject><subject>Aorta, Thoracic - diagnostic imaging</subject><subject>Aorta, Thoracic - immunology</subject><subject>Aorta, Thoracic - metabolism</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Atherosclerosis - diagnostic imaging</subject><subject>Atherosclerosis - immunology</subject><subject>Atherosclerosis - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Flow Velocity</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cardiology. Vascular system</subject><subject>Cell Adhesion - immunology</subject><subject>Disease Models, Animal</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Early Diagnosis</subject><subject>Echocardiography</subject><subject>Endothelial Cells - diagnostic imaging</subject><subject>Endothelial Cells - immunology</subject><subject>Endothelial Cells - metabolism</subject><subject>Heterogeneous-Nuclear Ribonucleoproteins - genetics</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>P-Selectin - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Receptors, LDL - genetics</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkVGP1CAQx4nReOfqF_DB9MX41HWA0i0-mNS709vkjIk5fSVTSndRWvagvct-e2m2OTUhzAC_-QPzJ-Q1hTWlJX1f3_78VF_XawpyTWXJq_IJOaeCFXlR8vJpymEjc1EW7Iy8iPEXABSMwXNyRmXFCwrinNx_9c7oyWHItj3u7LDLfJeNe5NtBztadCl2DvseRx-O2XcTD36IJrNDVicq-KjdPNv4IQkcnNU42kRknQ_ZFQZ3zC7NaPS8OStf2mgwmpfkWYcumldLXJEfn69uL67zm29fthf1Ta4LKiBvpWw0CoTWtEh514LQZZP-CqysSrahXIiuaThti05uOHQSqK7aBlBsWl4JviIfT7qHqelNq80wBnTqEGyP4ag8WvX_yWD3aufvFatoITgkgXeLQPB3k4mj6m3UxjkcjJ-i2qQ-SilS91eEnUid2hGD6R5voaBmv9TiV1pLdfIrFb35931_SxaDEvB2ATBqdF3AQdv4yDHGecUkS1xx4h68G02Iv930YILaG3TjXs3O8xJEzoDCPCCHOfI_WfSwPg</recordid><startdate>201001</startdate><enddate>201001</enddate><creator>Kaufmann, Beat A</creator><creator>Carr, Chad L</creator><creator>Belcik, J Todd</creator><creator>Xie, Aris</creator><creator>Yue, Qi</creator><creator>Chadderdon, Scott</creator><creator>Caplan, Evan S</creator><creator>Khangura, Jaspreet</creator><creator>Bullens, Sherry</creator><creator>Bunting, Stuart</creator><creator>Lindner, Jonathan R</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><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>5PM</scope></search><sort><creationdate>201001</creationdate><title>Molecular Imaging of the Initial Inflammatory Response in Atherosclerosis: Implications for Early Detection of Disease</title><author>Kaufmann, Beat A ; Carr, Chad L ; Belcik, J Todd ; Xie, Aris ; Yue, Qi ; Chadderdon, Scott ; Caplan, Evan S ; Khangura, Jaspreet ; Bullens, Sherry ; Bunting, Stuart ; Lindner, Jonathan R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4150-d99bca5a0deda13fd05c6b19602686271355fbb31d4f9730f901c8db0a57d3853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Aorta, Thoracic - diagnostic imaging</topic><topic>Aorta, Thoracic - immunology</topic><topic>Aorta, Thoracic - metabolism</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Atherosclerosis - diagnostic imaging</topic><topic>Atherosclerosis - immunology</topic><topic>Atherosclerosis - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood Flow Velocity</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cardiology. Vascular system</topic><topic>Cell Adhesion - immunology</topic><topic>Disease Models, Animal</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Early Diagnosis</topic><topic>Echocardiography</topic><topic>Endothelial Cells - diagnostic imaging</topic><topic>Endothelial Cells - immunology</topic><topic>Endothelial Cells - metabolism</topic><topic>Heterogeneous-Nuclear Ribonucleoproteins - genetics</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>P-Selectin - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenotype</topic><topic>Receptors, LDL - genetics</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaufmann, Beat A</creatorcontrib><creatorcontrib>Carr, Chad L</creatorcontrib><creatorcontrib>Belcik, J Todd</creatorcontrib><creatorcontrib>Xie, Aris</creatorcontrib><creatorcontrib>Yue, Qi</creatorcontrib><creatorcontrib>Chadderdon, Scott</creatorcontrib><creatorcontrib>Caplan, Evan S</creatorcontrib><creatorcontrib>Khangura, Jaspreet</creatorcontrib><creatorcontrib>Bullens, Sherry</creatorcontrib><creatorcontrib>Bunting, Stuart</creatorcontrib><creatorcontrib>Lindner, Jonathan R</creatorcontrib><collection>Pascal-Francis</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaufmann, Beat A</au><au>Carr, Chad L</au><au>Belcik, J Todd</au><au>Xie, Aris</au><au>Yue, Qi</au><au>Chadderdon, Scott</au><au>Caplan, Evan S</au><au>Khangura, Jaspreet</au><au>Bullens, Sherry</au><au>Bunting, Stuart</au><au>Lindner, Jonathan R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Imaging of the Initial Inflammatory Response in Atherosclerosis: Implications for Early Detection of Disease</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2010-01</date><risdate>2010</risdate><volume>30</volume><issue>1</issue><spage>54</spage><epage>59</epage><pages>54-59</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>BACKGROUND—We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could noninvasively evaluate prelesion atherogenic phenotype.
METHODS AND RESULTS—Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultrahigh frequency ultrasound, histology, and immunohistochemistry. In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement (P<0.01 versus nontargeted agent) at all ages for DKO mice. P-selectin and VCAM-1 signal in DKO mice were greater by 3-fold at 10 weeks, 4- to 6-fold at 20 weeks, and 9- to 10-fold at 40 weeks compared to wild-type mice. En face microscopy demonstrated preferential attachment of targeted microbubbles to regions of lesion formation.
CONCLUSIONS—Noninvasive ultrasound molecular imaging of endothelial activation can detect lesion-prone vascular phenotype before the appearance of obstructive atherosclerotic lesions.</abstract><cop>Philadelphia, PA</cop><pub>American Heart Association, Inc</pub><pmid>19834105</pmid><doi>10.1161/ATVBAHA.109.196386</doi><tpages>6</tpages></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2010-01, Vol.30 (1), p.54-59 |
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| subjects | Animals Aorta, Thoracic - diagnostic imaging Aorta, Thoracic - immunology Aorta, Thoracic - metabolism Atherosclerosis (general aspects, experimental research) Atherosclerosis - diagnostic imaging Atherosclerosis - immunology Atherosclerosis - metabolism Biological and medical sciences Blood and lymphatic vessels Blood Flow Velocity Blood. Blood coagulation. Reticuloendothelial system Cardiology. Vascular system Cell Adhesion - immunology Disease Models, Animal Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Early Diagnosis Echocardiography Endothelial Cells - diagnostic imaging Endothelial Cells - immunology Endothelial Cells - metabolism Heterogeneous-Nuclear Ribonucleoproteins - genetics Immunohistochemistry Medical sciences Mice Mice, Inbred C57BL Mice, Knockout P-Selectin - metabolism Pharmacology. Drug treatments Phenotype Receptors, LDL - genetics Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Molecular Imaging of the Initial Inflammatory Response in Atherosclerosis: Implications for Early Detection of Disease |
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