Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination
The cuprizone mouse model of demyelination was used to investigate the influence that white matter changes have on different magnetic resonance imaging results. In vivo T2‐weighted and magnetization transfer images (MTIs) were acquired weekly in control (n = 5) and cuprizone‐fed (n = 5) mice, with s...
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| Veröffentlicht in: | NMR in biomedicine 2013-11, Vol.26 (11), p.1562-1581 |
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| creator | Thiessen, Jonathan D. Zhang, Yanbo Zhang, Handi Wang, Lingyan Buist, Richard Del Bigio, Marc R. Kong, Jiming Li, Xin-Min Martin, Melanie |
| description | The cuprizone mouse model of demyelination was used to investigate the influence that white matter changes have on different magnetic resonance imaging results. In vivo T2‐weighted and magnetization transfer images (MTIs) were acquired weekly in control (n = 5) and cuprizone‐fed (n = 5) mice, with significant increases in signal intensity in T2‐weighted images (p |
| doi_str_mv | 10.1002/nbm.2992 |
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Cellular features in electron micrographs of the corpus callosum were correlated to several different quantitative MRI metrics. The largest Spearman correlation coefficient varied depending on cellular type: T1 versus the myelinated axon fraction (ρ = −0.90), the bound pool fraction (ƒ) versus the myelin sheath fraction (ρ = 0.93), and axial diffusivity versus the non‐myelinated cell fraction (ρ = 0.92). ƒ was the strongest indicator of myelin content while longitudinal relaxation rates and diffusivity measurements were the strongest indicators of changes in tissue structure.</description><identifier>ISSN: 0952-3480</identifier><identifier>EISSN: 1099-1492</identifier><identifier>DOI: 10.1002/nbm.2992</identifier><identifier>PMID: 23943390</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Animal models ; Animals ; Axons - pathology ; Axons - ultrastructure ; bound water fraction ; corpus callosum ; Corpus Callosum - pathology ; Corpus Callosum - ultrastructure ; Cuprizone ; Demyelinating Diseases - chemically induced ; Demyelinating Diseases - pathology ; demyelination ; Diet ; diffusion tensor imaging ; Disease Models, Animal ; electron microscopy ; Female ; Magnetic Resonance Imaging ; magnetization transfer imaging ; Mice ; Mice, Inbred C57BL ; Myelin Sheath - metabolism ; Perfusion ; Signal Processing, Computer-Assisted ; Statistics, Nonparametric ; T1/T2 relaxation time measurements</subject><ispartof>NMR in biomedicine, 2013-11, Vol.26 (11), p.1562-1581</ispartof><rights>Copyright © 2013 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4862-834642c5baef975f45efaf87885e09d46c90f52380ab7904f3b669d019e2c6c3</citedby><cites>FETCH-LOGICAL-c4862-834642c5baef975f45efaf87885e09d46c90f52380ab7904f3b669d019e2c6c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fnbm.2992$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fnbm.2992$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23943390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thiessen, Jonathan D.</creatorcontrib><creatorcontrib>Zhang, Yanbo</creatorcontrib><creatorcontrib>Zhang, Handi</creatorcontrib><creatorcontrib>Wang, Lingyan</creatorcontrib><creatorcontrib>Buist, Richard</creatorcontrib><creatorcontrib>Del Bigio, Marc R.</creatorcontrib><creatorcontrib>Kong, Jiming</creatorcontrib><creatorcontrib>Li, Xin-Min</creatorcontrib><creatorcontrib>Martin, Melanie</creatorcontrib><title>Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination</title><title>NMR in biomedicine</title><addtitle>NMR Biomed</addtitle><description>The cuprizone mouse model of demyelination was used to investigate the influence that white matter changes have on different magnetic resonance imaging results. In vivo T2‐weighted and magnetization transfer images (MTIs) were acquired weekly in control (n = 5) and cuprizone‐fed (n = 5) mice, with significant increases in signal intensity in T2‐weighted images (p < 0.001) and lower magnetization transfer ratio (p < 0.001) in the corpus callosum of the cuprizone‐fed mice starting at 3 weeks and peaking at 4 and 5 weeks, respectively. Diffusion tensor imaging (DTI), quantitative MTI (qMTI), and T1/T2 measurements were used to analyze freshly excised tissue after 6 weeks of cuprizone administration. In multicomponent T2 analysis with 10 ms echo spacing, there was no visible myelin water component associated with the short T2 value. Quantitative MTI metrics showed significant differences in the corpus callosum and external capsule of the cuprizone‐fed mice, similar to previous studies of multiple sclerosis in humans and animal models of demyelination. Fractional anisotropy was significantly lower and mean, axial, and radial diffusivity were significantly higher in the cuprizone‐fed mice. Cellular distributions measured in electron micrographs of the corpus callosum correlated strongly to several different quantitative MRI metrics. The largest Spearman correlation coefficient varied depending on cellular type: T1 versus the myelinated axon fraction (ρ = −0.90), the bound pool fraction (ƒ) versus the myelin sheath fraction (ρ = 0.93), and axial diffusivity versus the non‐myelinated cell fraction (ρ = 0.92). Using Pearson's correlation coefficient, ƒ was strongly correlated to the myelin sheath fraction (r = 0.98) with a linear equation predicting myelin content (5.37ƒ − 0.25). Of the calculated MRI metrics, ƒ was the strongest indicator of myelin content, while longitudinal relaxation rates and diffusivity measurements were the strongest indicators of changes in tissue structure. Copyright © 2013 John Wiley & Sons, Ltd.
Cellular features in electron micrographs of the corpus callosum were correlated to several different quantitative MRI metrics. The largest Spearman correlation coefficient varied depending on cellular type: T1 versus the myelinated axon fraction (ρ = −0.90), the bound pool fraction (ƒ) versus the myelin sheath fraction (ρ = 0.93), and axial diffusivity versus the non‐myelinated cell fraction (ρ = 0.92). ƒ was the strongest indicator of myelin content while longitudinal relaxation rates and diffusivity measurements were the strongest indicators of changes in tissue structure.</description><subject>Animal models</subject><subject>Animals</subject><subject>Axons - pathology</subject><subject>Axons - ultrastructure</subject><subject>bound water fraction</subject><subject>corpus callosum</subject><subject>Corpus Callosum - pathology</subject><subject>Corpus Callosum - ultrastructure</subject><subject>Cuprizone</subject><subject>Demyelinating Diseases - chemically induced</subject><subject>Demyelinating Diseases - pathology</subject><subject>demyelination</subject><subject>Diet</subject><subject>diffusion tensor imaging</subject><subject>Disease Models, Animal</subject><subject>electron microscopy</subject><subject>Female</subject><subject>Magnetic Resonance Imaging</subject><subject>magnetization transfer imaging</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myelin Sheath - metabolism</subject><subject>Perfusion</subject><subject>Signal Processing, Computer-Assisted</subject><subject>Statistics, Nonparametric</subject><subject>T1/T2 relaxation time measurements</subject><issn>0952-3480</issn><issn>1099-1492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0UtrFjEUBuAgFvtZBX-BDLhxM_VMkskkS7-ivdhWKkVdGTKZMzh1Lm0u2q-_vhk6rVAQ3OQs8vCSnJeQVwXsFgD03VgPu1Qp-oSsClAqL7iiT8kKVElzxiVsk-feXwCA5Iw-I9uUKc6YghX5cRbNGLpgQvcbs5Mvh5kZmyz2wRkfXLQhOtNneG2GbkxmGrOpzcJPzGy8dN3NNGI2TNHPZ4P9fNngsMF-0S_IVmt6jy-XuUPOP3443zvIjz_vH-69P84tl4LmknHBqS1rg62qypaX2JpWVlKWCKrhwipoS8okmLpSwFtWC6EaKBRSKyzbIW_vYi_ddBXRBz103mLfmxHT6_S8D0FVBeV_UM44CFmpRN88ohdTdGP6R1JCUC5YBX8DrZu8d9jqtJjBuI0uQM_t6NSOnttJ9PUSGOsBmwd4X0cC-R340_W4-WeQPl2fLIGL73zA6wdv3C8tKlaV-tvpvv4k10dn66_f9QG7Bd4Pp3k</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Thiessen, Jonathan D.</creator><creator>Zhang, Yanbo</creator><creator>Zhang, Handi</creator><creator>Wang, Lingyan</creator><creator>Buist, Richard</creator><creator>Del Bigio, Marc R.</creator><creator>Kong, Jiming</creator><creator>Li, Xin-Min</creator><creator>Martin, Melanie</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>201311</creationdate><title>Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination</title><author>Thiessen, Jonathan D. ; Zhang, Yanbo ; Zhang, Handi ; Wang, Lingyan ; Buist, Richard ; Del Bigio, Marc R. ; Kong, Jiming ; Li, Xin-Min ; Martin, Melanie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4862-834642c5baef975f45efaf87885e09d46c90f52380ab7904f3b669d019e2c6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Axons - pathology</topic><topic>Axons - ultrastructure</topic><topic>bound water fraction</topic><topic>corpus callosum</topic><topic>Corpus Callosum - pathology</topic><topic>Corpus Callosum - ultrastructure</topic><topic>Cuprizone</topic><topic>Demyelinating Diseases - chemically induced</topic><topic>Demyelinating Diseases - pathology</topic><topic>demyelination</topic><topic>Diet</topic><topic>diffusion tensor imaging</topic><topic>Disease Models, Animal</topic><topic>electron microscopy</topic><topic>Female</topic><topic>Magnetic Resonance Imaging</topic><topic>magnetization transfer imaging</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myelin Sheath - metabolism</topic><topic>Perfusion</topic><topic>Signal Processing, Computer-Assisted</topic><topic>Statistics, Nonparametric</topic><topic>T1/T2 relaxation time measurements</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thiessen, Jonathan D.</creatorcontrib><creatorcontrib>Zhang, Yanbo</creatorcontrib><creatorcontrib>Zhang, Handi</creatorcontrib><creatorcontrib>Wang, Lingyan</creatorcontrib><creatorcontrib>Buist, Richard</creatorcontrib><creatorcontrib>Del Bigio, Marc R.</creatorcontrib><creatorcontrib>Kong, Jiming</creatorcontrib><creatorcontrib>Li, Xin-Min</creatorcontrib><creatorcontrib>Martin, Melanie</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>NMR in biomedicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thiessen, Jonathan D.</au><au>Zhang, Yanbo</au><au>Zhang, Handi</au><au>Wang, Lingyan</au><au>Buist, Richard</au><au>Del Bigio, Marc R.</au><au>Kong, Jiming</au><au>Li, Xin-Min</au><au>Martin, Melanie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination</atitle><jtitle>NMR in biomedicine</jtitle><addtitle>NMR Biomed</addtitle><date>2013-11</date><risdate>2013</risdate><volume>26</volume><issue>11</issue><spage>1562</spage><epage>1581</epage><pages>1562-1581</pages><issn>0952-3480</issn><eissn>1099-1492</eissn><abstract>The cuprizone mouse model of demyelination was used to investigate the influence that white matter changes have on different magnetic resonance imaging results. In vivo T2‐weighted and magnetization transfer images (MTIs) were acquired weekly in control (n = 5) and cuprizone‐fed (n = 5) mice, with significant increases in signal intensity in T2‐weighted images (p < 0.001) and lower magnetization transfer ratio (p < 0.001) in the corpus callosum of the cuprizone‐fed mice starting at 3 weeks and peaking at 4 and 5 weeks, respectively. Diffusion tensor imaging (DTI), quantitative MTI (qMTI), and T1/T2 measurements were used to analyze freshly excised tissue after 6 weeks of cuprizone administration. In multicomponent T2 analysis with 10 ms echo spacing, there was no visible myelin water component associated with the short T2 value. Quantitative MTI metrics showed significant differences in the corpus callosum and external capsule of the cuprizone‐fed mice, similar to previous studies of multiple sclerosis in humans and animal models of demyelination. Fractional anisotropy was significantly lower and mean, axial, and radial diffusivity were significantly higher in the cuprizone‐fed mice. Cellular distributions measured in electron micrographs of the corpus callosum correlated strongly to several different quantitative MRI metrics. The largest Spearman correlation coefficient varied depending on cellular type: T1 versus the myelinated axon fraction (ρ = −0.90), the bound pool fraction (ƒ) versus the myelin sheath fraction (ρ = 0.93), and axial diffusivity versus the non‐myelinated cell fraction (ρ = 0.92). Using Pearson's correlation coefficient, ƒ was strongly correlated to the myelin sheath fraction (r = 0.98) with a linear equation predicting myelin content (5.37ƒ − 0.25). Of the calculated MRI metrics, ƒ was the strongest indicator of myelin content, while longitudinal relaxation rates and diffusivity measurements were the strongest indicators of changes in tissue structure. Copyright © 2013 John Wiley & Sons, Ltd.
Cellular features in electron micrographs of the corpus callosum were correlated to several different quantitative MRI metrics. The largest Spearman correlation coefficient varied depending on cellular type: T1 versus the myelinated axon fraction (ρ = −0.90), the bound pool fraction (ƒ) versus the myelin sheath fraction (ρ = 0.93), and axial diffusivity versus the non‐myelinated cell fraction (ρ = 0.92). ƒ was the strongest indicator of myelin content while longitudinal relaxation rates and diffusivity measurements were the strongest indicators of changes in tissue structure.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23943390</pmid><doi>10.1002/nbm.2992</doi><tpages>20</tpages></addata></record> |
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| subjects | Animal models Animals Axons - pathology Axons - ultrastructure bound water fraction corpus callosum Corpus Callosum - pathology Corpus Callosum - ultrastructure Cuprizone Demyelinating Diseases - chemically induced Demyelinating Diseases - pathology demyelination Diet diffusion tensor imaging Disease Models, Animal electron microscopy Female Magnetic Resonance Imaging magnetization transfer imaging Mice Mice, Inbred C57BL Myelin Sheath - metabolism Perfusion Signal Processing, Computer-Assisted Statistics, Nonparametric T1/T2 relaxation time measurements |
| title | Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination |
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