A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers.
Identifieur interne : 000352 ( PubMed/Checkpoint ); précédent : 000351; suivant : 000353A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers.
Auteurs : Aaron Sturrock [Canada] ; Corree Laule ; Katy Wyper ; Ruth A. Milner ; Joji Decolongon ; Rachelle Dar Santos ; Allison J. Coleman ; Kimberley Carter ; Susan Creighton ; Natalie Bechtel ; Stefan Bohlen ; Ralf Reilmann ; Hans J. Johnson ; Michael R. Hayden ; Sarah J. Tabrizi ; Alex L. Mackay ; Blair R. LeavittSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2015.
Abstract
Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts.
DOI: 10.1002/mds.26118
PubMed: 25690257
Affiliations:
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Milner</name></author><author><name sortKey="Decolongon, Joji" sort="Decolongon, Joji" uniqKey="Decolongon J" first="Joji" last="Decolongon">Joji Decolongon</name></author><author><name sortKey="Dar Santos, Rachelle" sort="Dar Santos, Rachelle" uniqKey="Dar Santos R" first="Rachelle" last="Dar Santos">Rachelle Dar Santos</name></author><author><name sortKey="Coleman, Allison J" sort="Coleman, Allison J" uniqKey="Coleman A" first="Allison J" last="Coleman">Allison J. 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Leavitt</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25690257</idno><idno type="pmid">25690257</idno><idno type="doi">10.1002/mds.26118</idno><idno type="wicri:Area/PubMed/Corpus">000256</idno><idno type="wicri:Area/PubMed/Curation">000256</idno><idno type="wicri:Area/PubMed/Checkpoint">000352</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers.</title><author><name sortKey="Sturrock, Aaron" sort="Sturrock, Aaron" uniqKey="Sturrock A" first="Aaron" last="Sturrock">Aaron Sturrock</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Molecular Medicine & Therapeutics, Vancouver, Canada; Centre for Huntington Disease, University of British Columbia (UBC) Hospital, Vancouver, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Molecular Medicine & Therapeutics, Vancouver, Canada; Centre for Huntington Disease, University of British Columbia (UBC) Hospital, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author><author><name sortKey="Laule, Corree" sort="Laule, Corree" uniqKey="Laule C" first="Corree" last="Laule">Corree Laule</name></author><author><name sortKey="Wyper, Katy" sort="Wyper, Katy" uniqKey="Wyper K" first="Katy" last="Wyper">Katy Wyper</name></author><author><name sortKey="Milner, Ruth A" sort="Milner, Ruth A" uniqKey="Milner R" first="Ruth A" last="Milner">Ruth A. Milner</name></author><author><name sortKey="Decolongon, Joji" sort="Decolongon, Joji" uniqKey="Decolongon J" first="Joji" last="Decolongon">Joji Decolongon</name></author><author><name sortKey="Dar Santos, Rachelle" sort="Dar Santos, Rachelle" uniqKey="Dar Santos R" first="Rachelle" last="Dar Santos">Rachelle Dar Santos</name></author><author><name sortKey="Coleman, Allison J" sort="Coleman, Allison J" uniqKey="Coleman A" first="Allison J" last="Coleman">Allison J. Coleman</name></author><author><name sortKey="Carter, Kimberley" sort="Carter, Kimberley" uniqKey="Carter K" first="Kimberley" last="Carter">Kimberley Carter</name></author><author><name sortKey="Creighton, Susan" sort="Creighton, Susan" uniqKey="Creighton S" first="Susan" last="Creighton">Susan Creighton</name></author><author><name sortKey="Bechtel, Natalie" sort="Bechtel, Natalie" uniqKey="Bechtel N" first="Natalie" last="Bechtel">Natalie Bechtel</name></author><author><name sortKey="Bohlen, Stefan" sort="Bohlen, Stefan" uniqKey="Bohlen S" first="Stefan" last="Bohlen">Stefan Bohlen</name></author><author><name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name></author><author><name sortKey="Johnson, Hans J" sort="Johnson, Hans J" uniqKey="Johnson H" first="Hans J" last="Johnson">Hans J. Johnson</name></author><author><name sortKey="Hayden, Michael R" sort="Hayden, Michael R" uniqKey="Hayden M" first="Michael R" last="Hayden">Michael R. Hayden</name></author><author><name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. Tabrizi</name></author><author><name sortKey="Mackay, Alex L" sort="Mackay, Alex L" uniqKey="Mackay A" first="Alex L" last="Mackay">Alex L. Mackay</name></author><author><name sortKey="Leavitt, Blair R" sort="Leavitt, Blair R" uniqKey="Leavitt B" first="Blair R" last="Leavitt">Blair R. Leavitt</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="In-Process"><PMID Version="1">25690257</PMID><DateCreated><Year>2015</Year><Month>03</Month><Day>11</Day></DateCreated><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>30</Volume><Issue>3</Issue><PubDate><Year>2015</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers.</ArticleTitle><Pagination><MedlinePgn>393-401</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.26118</ELocationID><Abstract><AbstractText>Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts.</AbstractText><CopyrightInformation>© 2015 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sturrock</LastName><ForeName>Aaron</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Centre for Molecular Medicine & Therapeutics, Vancouver, Canada; Centre for Huntington Disease, University of British Columbia (UBC) Hospital, Vancouver, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laule</LastName><ForeName>Corree</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Wyper</LastName><ForeName>Katy</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Milner</LastName><ForeName>Ruth A</ForeName><Initials>RA</Initials></Author><Author ValidYN="Y"><LastName>Decolongon</LastName><ForeName>Joji</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Dar Santos</LastName><ForeName>Rachelle</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Coleman</LastName><ForeName>Allison J</ForeName><Initials>AJ</Initials></Author><Author ValidYN="Y"><LastName>Carter</LastName><ForeName>Kimberley</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Creighton</LastName><ForeName>Susan</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Bechtel</LastName><ForeName>Natalie</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Bohlen</LastName><ForeName>Stefan</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Reilmann</LastName><ForeName>Ralf</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Johnson</LastName><ForeName>Hans J</ForeName><Initials>HJ</Initials></Author><Author ValidYN="Y"><LastName>Hayden</LastName><ForeName>Michael R</ForeName><Initials>MR</Initials></Author><Author ValidYN="Y"><LastName>Tabrizi</LastName><ForeName>Sarah J</ForeName><Initials>SJ</Initials></Author><Author ValidYN="Y"><LastName>Mackay</LastName><ForeName>Alex L</ForeName><Initials>AL</Initials></Author><Author ValidYN="Y"><LastName>Leavitt</LastName><ForeName>Blair R</ForeName><Initials>BR</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>20R-03189</GrantID><Agency>PHS HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>02</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Huntington's disease</Keyword><Keyword MajorTopicYN="N">MRI</Keyword><Keyword MajorTopicYN="N">MRS</Keyword><Keyword MajorTopicYN="N">N-acetyl aspartate (NAA)</Keyword><Keyword MajorTopicYN="N">myo-inositol (MI)</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>5</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2014</Year><Month>10</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>10</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="aheadofprint"><Year>2015</Year><Month>2</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>2</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>2</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>2</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25690257</ArticleId><ArticleId IdType="doi">10.1002/mds.26118</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Bechtel, Natalie" sort="Bechtel, Natalie" uniqKey="Bechtel N" first="Natalie" last="Bechtel">Natalie Bechtel</name><name sortKey="Bohlen, Stefan" sort="Bohlen, Stefan" uniqKey="Bohlen S" first="Stefan" last="Bohlen">Stefan Bohlen</name><name sortKey="Carter, Kimberley" sort="Carter, Kimberley" uniqKey="Carter K" first="Kimberley" last="Carter">Kimberley Carter</name><name sortKey="Coleman, Allison J" sort="Coleman, Allison J" uniqKey="Coleman A" first="Allison J" last="Coleman">Allison J. Coleman</name><name sortKey="Creighton, Susan" sort="Creighton, Susan" uniqKey="Creighton S" first="Susan" last="Creighton">Susan Creighton</name><name sortKey="Dar Santos, Rachelle" sort="Dar Santos, Rachelle" uniqKey="Dar Santos R" first="Rachelle" last="Dar Santos">Rachelle Dar Santos</name><name sortKey="Decolongon, Joji" sort="Decolongon, Joji" uniqKey="Decolongon J" first="Joji" last="Decolongon">Joji Decolongon</name><name sortKey="Hayden, Michael R" sort="Hayden, Michael R" uniqKey="Hayden M" first="Michael R" last="Hayden">Michael R. Hayden</name><name sortKey="Johnson, Hans J" sort="Johnson, Hans J" uniqKey="Johnson H" first="Hans J" last="Johnson">Hans J. Johnson</name><name sortKey="Laule, Corree" sort="Laule, Corree" uniqKey="Laule C" first="Corree" last="Laule">Corree Laule</name><name sortKey="Leavitt, Blair R" sort="Leavitt, Blair R" uniqKey="Leavitt B" first="Blair R" last="Leavitt">Blair R. Leavitt</name><name sortKey="Mackay, Alex L" sort="Mackay, Alex L" uniqKey="Mackay A" first="Alex L" last="Mackay">Alex L. Mackay</name><name sortKey="Milner, Ruth A" sort="Milner, Ruth A" uniqKey="Milner R" first="Ruth A" last="Milner">Ruth A. Milner</name><name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name><name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. Tabrizi</name><name sortKey="Wyper, Katy" sort="Wyper, Katy" uniqKey="Wyper K" first="Katy" last="Wyper">Katy Wyper</name></noCountry><country name="Canada"><noRegion><name sortKey="Sturrock, Aaron" sort="Sturrock, Aaron" uniqKey="Sturrock A" first="Aaron" last="Sturrock">Aaron Sturrock</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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