Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations

Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of cerebral blood flow and metabolism 2006-05, Vol.26 (5), p.645-653
Hauptverfasser: Strong, Anthony J, Bezzina, Elizabeth Lindsey, Anderson, Peter JB, Boutelle, Martyn G, Hopwood, Sarah E, Dunn, Andrew K
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 653
container_issue 5
container_start_page 645
container_title Journal of cerebral blood flow and metabolism
container_volume 26
creator Strong, Anthony J
Bezzina, Elizabeth Lindsey
Anderson, Peter JB
Boutelle, Martyn G
Hopwood, Sarah E
Dunn, Andrew K
description Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitively using umbelliferone clearance (CBFumb). Values of ICT and CBFumb were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT- and CBFumb-derived values of perfusion were closely correlated, with a high degree of significance (P < 0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements.
doi_str_mv 10.1038/sj.jcbfm.9600240
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67899815</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1038_sj.jcbfm.9600240</sage_id><sourcerecordid>67899815</sourcerecordid><originalsourceid>FETCH-LOGICAL-c458t-fd0ebeec9b927c6a213cb7301ae406797c8edb42f41f1f39bbf1fdfb9e740113</originalsourceid><addsrcrecordid>eNp1kU-P0zAQxS0EYsvCnROykOCWYjt_HHNDpQuVKgHaPXCLHGdcOZvYwXaA_U58SNxtRBESp3eY35t5mofQc0rWlOT1m9Cve9XqcS0qQlhBHqAVLUuRcUKrh2hFGKdZxeuvF-hJCD0hpM7L8jG6oBUraV0XK_Rr-10Os4zGWew03ssAHl9PoG4HwFeD-zFC9HdYO493ozwYe8Ab56NRcsCfwes5HJ3G4u3PCbwZwcY0uY7e3UKSuTMQ3uIvs7TRxD9nzk5pO_weIqi_RibbWS29imkyuUF6E-6d4Sl6pOUQ4Nmil-jmanuz-ZjtP33Ybd7tM1WUdcx0R6AFUKIVjKtKMpqrlueESihIxQVXNXRtwXRBNdW5aNsknW4F8IJQml-i16e1k3ffZgixGU1QMAzSgptDkz4qRE3LBL78B-zd7G2K1jAqyoIxctxGTpDyLgQPupnSn6S_ayhpji02oW_uW2yWFpPlxbJ3bkfozoaltgS8WgAZUhPaS6tMOHOcF1Tkx4DZiQvyAOdw_z38G-T1uhg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>219542201</pqid></control><display><type>article</type><title>Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations</title><source>MEDLINE</source><source>SAGE Complete</source><creator>Strong, Anthony J ; Bezzina, Elizabeth Lindsey ; Anderson, Peter JB ; Boutelle, Martyn G ; Hopwood, Sarah E ; Dunn, Andrew K</creator><creatorcontrib>Strong, Anthony J ; Bezzina, Elizabeth Lindsey ; Anderson, Peter JB ; Boutelle, Martyn G ; Hopwood, Sarah E ; Dunn, Andrew K</creatorcontrib><description>Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitively using umbelliferone clearance (CBFumb). Values of ICT and CBFumb were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT- and CBFumb-derived values of perfusion were closely correlated, with a high degree of significance (P &lt; 0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1038/sj.jcbfm.9600240</identifier><identifier>PMID: 16251884</identifier><identifier>CODEN: JCBMDN</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Biological and medical sciences ; Blood Flow Velocity ; Cats ; Cerebral Cortex - anatomy &amp; histology ; Cerebral Cortex - physiology ; Cerebrovascular Circulation ; Disease Models, Animal ; Electrophysiology ; Image Processing, Computer-Assisted ; Infarction, Middle Cerebral Artery ; Investigative techniques, diagnostic techniques (general aspects) ; Laser-Doppler Flowmetry - methods ; Medical sciences ; Nervous system ; Neurology ; Radiodiagnosis. Nmr imagery. Nmr spectrometry ; Regional Blood Flow ; Stroke - pathology ; Ultrasonic investigative techniques ; Umbelliferones - metabolism ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Journal of cerebral blood flow and metabolism, 2006-05, Vol.26 (5), p.645-653</ispartof><rights>2006 ISCBFM</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group May 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-fd0ebeec9b927c6a213cb7301ae406797c8edb42f41f1f39bbf1fdfb9e740113</citedby><cites>FETCH-LOGICAL-c458t-fd0ebeec9b927c6a213cb7301ae406797c8edb42f41f1f39bbf1fdfb9e740113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1038/sj.jcbfm.9600240$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1038/sj.jcbfm.9600240$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=17741935$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16251884$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strong, Anthony J</creatorcontrib><creatorcontrib>Bezzina, Elizabeth Lindsey</creatorcontrib><creatorcontrib>Anderson, Peter JB</creatorcontrib><creatorcontrib>Boutelle, Martyn G</creatorcontrib><creatorcontrib>Hopwood, Sarah E</creatorcontrib><creatorcontrib>Dunn, Andrew K</creatorcontrib><title>Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations</title><title>Journal of cerebral blood flow and metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitively using umbelliferone clearance (CBFumb). Values of ICT and CBFumb were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT- and CBFumb-derived values of perfusion were closely correlated, with a high degree of significance (P &lt; 0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Flow Velocity</subject><subject>Cats</subject><subject>Cerebral Cortex - anatomy &amp; histology</subject><subject>Cerebral Cortex - physiology</subject><subject>Cerebrovascular Circulation</subject><subject>Disease Models, Animal</subject><subject>Electrophysiology</subject><subject>Image Processing, Computer-Assisted</subject><subject>Infarction, Middle Cerebral Artery</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Laser-Doppler Flowmetry - methods</subject><subject>Medical sciences</subject><subject>Nervous system</subject><subject>Neurology</subject><subject>Radiodiagnosis. Nmr imagery. Nmr spectrometry</subject><subject>Regional Blood Flow</subject><subject>Stroke - pathology</subject><subject>Ultrasonic investigative techniques</subject><subject>Umbelliferones - metabolism</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU-P0zAQxS0EYsvCnROykOCWYjt_HHNDpQuVKgHaPXCLHGdcOZvYwXaA_U58SNxtRBESp3eY35t5mofQc0rWlOT1m9Cve9XqcS0qQlhBHqAVLUuRcUKrh2hFGKdZxeuvF-hJCD0hpM7L8jG6oBUraV0XK_Rr-10Os4zGWew03ssAHl9PoG4HwFeD-zFC9HdYO493ozwYe8Ab56NRcsCfwes5HJ3G4u3PCbwZwcY0uY7e3UKSuTMQ3uIvs7TRxD9nzk5pO_weIqi_RibbWS29imkyuUF6E-6d4Sl6pOUQ4Nmil-jmanuz-ZjtP33Ybd7tM1WUdcx0R6AFUKIVjKtKMpqrlueESihIxQVXNXRtwXRBNdW5aNsknW4F8IJQml-i16e1k3ffZgixGU1QMAzSgptDkz4qRE3LBL78B-zd7G2K1jAqyoIxctxGTpDyLgQPupnSn6S_ayhpji02oW_uW2yWFpPlxbJ3bkfozoaltgS8WgAZUhPaS6tMOHOcF1Tkx4DZiQvyAOdw_z38G-T1uhg</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>Strong, Anthony J</creator><creator>Bezzina, Elizabeth Lindsey</creator><creator>Anderson, Peter JB</creator><creator>Boutelle, Martyn G</creator><creator>Hopwood, Sarah E</creator><creator>Dunn, Andrew K</creator><general>SAGE Publications</general><general>Lippincott Williams &amp; Wilkins</general><general>Sage Publications Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20060501</creationdate><title>Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations</title><author>Strong, Anthony J ; Bezzina, Elizabeth Lindsey ; Anderson, Peter JB ; Boutelle, Martyn G ; Hopwood, Sarah E ; Dunn, Andrew K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-fd0ebeec9b927c6a213cb7301ae406797c8edb42f41f1f39bbf1fdfb9e740113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Flow Velocity</topic><topic>Cats</topic><topic>Cerebral Cortex - anatomy &amp; histology</topic><topic>Cerebral Cortex - physiology</topic><topic>Cerebrovascular Circulation</topic><topic>Disease Models, Animal</topic><topic>Electrophysiology</topic><topic>Image Processing, Computer-Assisted</topic><topic>Infarction, Middle Cerebral Artery</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Laser-Doppler Flowmetry - methods</topic><topic>Medical sciences</topic><topic>Nervous system</topic><topic>Neurology</topic><topic>Radiodiagnosis. Nmr imagery. Nmr spectrometry</topic><topic>Regional Blood Flow</topic><topic>Stroke - pathology</topic><topic>Ultrasonic investigative techniques</topic><topic>Umbelliferones - metabolism</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strong, Anthony J</creatorcontrib><creatorcontrib>Bezzina, Elizabeth Lindsey</creatorcontrib><creatorcontrib>Anderson, Peter JB</creatorcontrib><creatorcontrib>Boutelle, Martyn G</creatorcontrib><creatorcontrib>Hopwood, Sarah E</creatorcontrib><creatorcontrib>Dunn, Andrew K</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>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</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>Journal of cerebral blood flow and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strong, Anthony J</au><au>Bezzina, Elizabeth Lindsey</au><au>Anderson, Peter JB</au><au>Boutelle, Martyn G</au><au>Hopwood, Sarah E</au><au>Dunn, Andrew K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations</atitle><jtitle>Journal of cerebral blood flow and metabolism</jtitle><addtitle>J Cereb Blood Flow Metab</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>26</volume><issue>5</issue><spage>645</spage><epage>653</epage><pages>645-653</pages><issn>0271-678X</issn><eissn>1559-7016</eissn><coden>JCBMDN</coden><abstract>Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitively using umbelliferone clearance (CBFumb). Values of ICT and CBFumb were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT- and CBFumb-derived values of perfusion were closely correlated, with a high degree of significance (P &lt; 0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>16251884</pmid><doi>10.1038/sj.jcbfm.9600240</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0271-678X
ispartof Journal of cerebral blood flow and metabolism, 2006-05, Vol.26 (5), p.645-653
issn 0271-678X
1559-7016
language eng
recordid cdi_proquest_miscellaneous_67899815
source MEDLINE; SAGE Complete
subjects Animals
Biological and medical sciences
Blood Flow Velocity
Cats
Cerebral Cortex - anatomy & histology
Cerebral Cortex - physiology
Cerebrovascular Circulation
Disease Models, Animal
Electrophysiology
Image Processing, Computer-Assisted
Infarction, Middle Cerebral Artery
Investigative techniques, diagnostic techniques (general aspects)
Laser-Doppler Flowmetry - methods
Medical sciences
Nervous system
Neurology
Radiodiagnosis. Nmr imagery. Nmr spectrometry
Regional Blood Flow
Stroke - pathology
Ultrasonic investigative techniques
Umbelliferones - metabolism
Vascular diseases and vascular malformations of the nervous system
title Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T14%3A29%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20Laser%20Speckle%20Flowmetry%20for%20Imaging%20Cortical%20Perfusion%20in%20Experimental%20Stroke%20Studies:%20Quantitation%20of%20Perfusion%20and%20Detection%20of%20Peri-Infarct%20Depolarisations&rft.jtitle=Journal%20of%20cerebral%20blood%20flow%20and%20metabolism&rft.au=Strong,%20Anthony%20J&rft.date=2006-05-01&rft.volume=26&rft.issue=5&rft.spage=645&rft.epage=653&rft.pages=645-653&rft.issn=0271-678X&rft.eissn=1559-7016&rft.coden=JCBMDN&rft_id=info:doi/10.1038/sj.jcbfm.9600240&rft_dat=%3Cproquest_cross%3E67899815%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=219542201&rft_id=info:pmid/16251884&rft_sage_id=10.1038_sj.jcbfm.9600240&rfr_iscdi=true