Imaging of Metastatic Lymph Nodes by X-ray Phase-Contrast Micro-Tomography
Identifieur interne : 004466 ( Pmc/Curation ); précédent : 004465; suivant : 004467Imaging of Metastatic Lymph Nodes by X-ray Phase-Contrast Micro-Tomography
Auteurs : Torben Haugaard Jensen [Danemark] ; Martin Bech [Allemagne, Suède] ; Tina Binderup [Danemark] ; Arvid Böttiger [Danemark] ; Christian David [Suisse] ; Timm Weitkamp [France] ; Irene Zanette [Allemagne, France] ; Elena Reznikova [Allemagne] ; Jürgen Mohr [Allemagne] ; Fritz Rank [Danemark] ; Robert Feidenhans [Danemark] ; Andreas Kj R [Danemark] ; Liselotte H Jgaard [Danemark] ; Franz Pfeiffer [Allemagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
Invasive cancer causes a change in density in the affected tissue, which can be visualized by x-ray phase-contrast tomography. However, the diagnostic value of this method has so far not been investigated in detail. Therefore, the purpose of this study was, in a blinded manner, to investigate whether malignancy could be revealed by non-invasive x-ray phase-contrast tomography in lymph nodes from breast cancer patients. Seventeen formalin-fixed paraffin-embedded lymph nodes from 10 female patients (age range 37–83 years) diagnosed with invasive ductal carcinomas were analyzed by X-ray phase-contrast tomography. Ten lymph nodes had metastatic deposits and 7 were benign. The phase-contrast images were analyzed according to standards for conventional CT images looking for characteristics usually only visible by pathological examinations. Histopathology was used as reference. The result of this study was that the diagnostic sensitivity of the image analysis for detecting malignancy was 100% and the specificity was 87%. The positive predictive value was 91% for detecting malignancy and the negative predictive value was 100%. We conclude that x-ray phase-contrast imaging can accurately detect density variations to obtain information regarding lymph node involvement previously inaccessible with standard absorption x-ray imaging.
Url:
DOI: 10.1371/journal.pone.0054047
PubMed: 23349784
PubMed Central: 3548812
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sortKey="Jensen, Torben Haugaard" sort="Jensen, Torben Haugaard" uniqKey="Jensen T" first="Torben Haugaard" last="Jensen">Torben Haugaard Jensen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Niels Bohr Institute, University of Copenhagen, Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Bech, Martin" sort="Bech, Martin" uniqKey="Bech M" first="Martin" last="Bech">Martin Bech</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Physics, Technische Universität München, Munich, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Physics, Technische Universität München, Munich</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Medical Radiation Physics, Lund University, Lund, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Medical Radiation Physics, Lund University, Lund</wicri:regionArea></affiliation></author><author><name sortKey="Binderup, Tina" sort="Binderup, Tina" uniqKey="Binderup T" first="Tina" last="Binderup">Tina Binderup</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Cluster for Molecular Imaging, University of Copenhagen, Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Bottiger, Arvid" sort="Bottiger, Arvid" uniqKey="Bottiger A" first="Arvid" last="Böttiger">Arvid Böttiger</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Niels Bohr Institute, University of Copenhagen, Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="David, Christian" sort="David, Christian" uniqKey="David C" first="Christian" last="David">Christian David</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Paul Scherrer Institut, Villigen, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Paul Scherrer Institut, Villigen</wicri:regionArea></affiliation></author><author><name sortKey="Weitkamp, Timm" sort="Weitkamp, Timm" uniqKey="Weitkamp T" first="Timm" last="Weitkamp">Timm Weitkamp</name><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>Synchrotron Soleil, Gif-sur-Yvette, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Synchrotron Soleil, Gif-sur-Yvette</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>European Synchrotron Radiation Facility, Grenoble, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>European Synchrotron Radiation Facility, Grenoble</wicri:regionArea></affiliation></author><author><name sortKey="Zanette, Irene" sort="Zanette, Irene" uniqKey="Zanette I" first="Irene" last="Zanette">Irene Zanette</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Physics, Technische Universität München, Munich, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Physics, Technische Universität München, Munich</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>European Synchrotron Radiation Facility, Grenoble, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>European Synchrotron Radiation Facility, Grenoble</wicri:regionArea></affiliation></author><author><name sortKey="Reznikova, Elena" sort="Reznikova, Elena" uniqKey="Reznikova E" first="Elena" last="Reznikova">Elena Reznikova</name><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Institute for Microstructure Technology, Karlsruhe Institute of Technology, Karlsruhe, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Microstructure Technology, Karlsruhe Institute of Technology, Karlsruhe</wicri:regionArea></affiliation></author><author><name sortKey="Mohr, Jurgen" sort="Mohr, Jurgen" uniqKey="Mohr J" first="Jürgen" last="Mohr">Jürgen Mohr</name><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Institute for Microstructure Technology, Karlsruhe Institute of Technology, Karlsruhe, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Microstructure Technology, Karlsruhe Institute of Technology, Karlsruhe</wicri:regionArea></affiliation></author><author><name sortKey="Rank, Fritz" sort="Rank, Fritz" uniqKey="Rank F" first="Fritz" last="Rank">Fritz Rank</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Feidenhans, Robert" sort="Feidenhans, Robert" uniqKey="Feidenhans R" first="Robert" last="Feidenhans">Robert Feidenhans</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Niels Bohr Institute, University of Copenhagen, Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Kj R, Andreas" sort="Kj R, Andreas" uniqKey="Kj R A" first="Andreas" last="Kj R">Andreas Kj R</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Cluster for Molecular Imaging, University of Copenhagen, Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="H Jgaard, Liselotte" sort="H Jgaard, Liselotte" uniqKey="H Jgaard L" first="Liselotte" last="H Jgaard">Liselotte H Jgaard</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark</addr-line></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Cluster for Molecular Imaging, University of Copenhagen, Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Pfeiffer, Franz" sort="Pfeiffer, Franz" uniqKey="Pfeiffer F" first="Franz" last="Pfeiffer">Franz Pfeiffer</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Physics, Technische Universität München, Munich, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Physics, Technische Universität München, Munich</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Invasive cancer causes a change in density in the affected tissue, which can be visualized by x-ray phase-contrast tomography. However, the diagnostic value of this method has so far not been investigated in detail. Therefore, the purpose of this study was, in a blinded manner, to investigate whether malignancy could be revealed by non-invasive x-ray phase-contrast tomography in lymph nodes from breast cancer patients. Seventeen formalin-fixed paraffin-embedded lymph nodes from 10 female patients (age range 37–83 years) diagnosed with invasive ductal carcinomas were analyzed by X-ray phase-contrast tomography. Ten lymph nodes had metastatic deposits and 7 were benign. The phase-contrast images were analyzed according to standards for conventional CT images looking for characteristics usually only visible by pathological examinations. Histopathology was used as reference. The result of this study was that the diagnostic sensitivity of the image analysis for detecting malignancy was 100% and the specificity was 87%. The positive predictive value was 91% for detecting malignancy and the negative predictive value was 100%. We conclude that x-ray phase-contrast imaging can accurately detect density variations to obtain information regarding lymph node involvement previously inaccessible with standard absorption x-ray imaging.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J Ferlay</name></author><author><name sortKey="Autier, P" uniqKey="Autier P">P Autier</name></author><author><name sortKey="Boniol, M" uniqKey="Boniol M">M Boniol</name></author><author><name sortKey="Heanue, M" uniqKey="Heanue M">M Heanue</name></author><author><name sortKey="Colombet, M" uniqKey="Colombet M">M Colombet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Veronesi, U" uniqKey="Veronesi U">U Veronesi</name></author><author><name sortKey="Paganelli, G" uniqKey="Paganelli G">G Paganelli</name></author><author><name sortKey="Viale, G" uniqKey="Viale G">G Viale</name></author><author><name sortKey="Luini, A" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23349784</article-id><article-id pub-id-type="pmc">3548812</article-id><article-id pub-id-type="publisher-id">PONE-D-12-22238</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0054047</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Anatomy and Physiology</subject><subj-group><subject>Immune Physiology</subject><subj-group><subject>Lymphatic System</subject></subj-group></subj-group></subj-group><subj-group><subject>Immunology</subject><subj-group><subject>Immune System</subject><subj-group><subject>Lymphoid Organs</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Anatomy and Physiology</subject><subj-group><subject>Immune Physiology</subject><subj-group><subject>Lymphatic System</subject></subj-group></subj-group></subj-group><subj-group><subject>Hematology</subject><subj-group><subject>Hematologic Cancers and Related Disorders</subject><subj-group><subject>Lymphomas</subject></subj-group></subj-group></subj-group><subj-group><subject>Oncology</subject><subj-group><subject>Cancers and Neoplasms</subject><subj-group><subject>Breast Tumors</subject><subj-group><subject>Ductal Carcinoma in Situ</subject><subject>Invasive Ductal Carcinoma</subject></subj-group></subj-group><subj-group><subject>Hematologic Cancers and Related Disorders</subject><subj-group><subject>Lymphomas</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Physics</subject><subj-group><subject>Electromagnetic Radiation</subject><subj-group><subject>X-Rays</subject></subj-group></subj-group><subj-group><subject>Medical Physics</subject></subj-group></subj-group></article-categories><title-group><article-title>Imaging of Metastatic Lymph Nodes by X-ray Phase-Contrast Micro-Tomography</article-title><alt-title alt-title-type="running-head">Imaging of Lymph Nodes by X-ray Phase-Contrast</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Jensen</surname><given-names>Torben Haugaard</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bech</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Binderup</surname><given-names>Tina</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Böttiger</surname><given-names>Arvid</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>David</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Weitkamp</surname><given-names>Timm</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zanette</surname><given-names>Irene</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reznikova</surname><given-names>Elena</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mohr</surname><given-names>Jürgen</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rank</surname><given-names>Fritz</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Feidenhans’l</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kjær</surname><given-names>Andreas</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Højgaard</surname><given-names>Liselotte</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pfeiffer</surname><given-names>Franz</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Physics, Technische Universität München, Munich, Germany</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Medical Radiation Physics, Lund University, Lund, Sweden</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Dept. of Clinical Physiology, Rigshospitalet, Copenhagen, Denmark</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark</addr-line></aff><aff id="aff6"><label>6</label><addr-line>Paul Scherrer Institut, Villigen, Switzerland</addr-line></aff><aff id="aff7"><label>7</label><addr-line>Synchrotron Soleil, Gif-sur-Yvette, France</addr-line></aff><aff id="aff8"><label>8</label><addr-line>European Synchrotron Radiation Facility, Grenoble, France</addr-line></aff><aff id="aff9"><label>9</label><addr-line>Institute for Microstructure Technology, Karlsruhe Institute of Technology, Karlsruhe, Germany</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Slominski</surname><given-names>Andrzej T.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Tennessee, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>martin.bech@tum.de</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: THJ MB TB RF AK LH FP. Performed the experiments: THJ MB TB AB TW IZ FR RF. Analyzed the data: THJ MB TB AB FR AK. Contributed reagents/materials/analysis tools: CD TW IZ ER JM. Wrote the paper: THJ MB TB.</p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>18</day><month>1</month><year>2013</year></pub-date><volume>8</volume><issue>1</issue><elocation-id>e54047</elocation-id><history><date date-type="received"><day>26</day><month>7</month><year>2012</year></date><date date-type="accepted"><day>6</day><month>12</month><year>2012</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Jensen et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>Invasive cancer causes a change in density in the affected tissue, which can be visualized by x-ray phase-contrast tomography. However, the diagnostic value of this method has so far not been investigated in detail. Therefore, the purpose of this study was, in a blinded manner, to investigate whether malignancy could be revealed by non-invasive x-ray phase-contrast tomography in lymph nodes from breast cancer patients. Seventeen formalin-fixed paraffin-embedded lymph nodes from 10 female patients (age range 37–83 years) diagnosed with invasive ductal carcinomas were analyzed by X-ray phase-contrast tomography. Ten lymph nodes had metastatic deposits and 7 were benign. The phase-contrast images were analyzed according to standards for conventional CT images looking for characteristics usually only visible by pathological examinations. Histopathology was used as reference. The result of this study was that the diagnostic sensitivity of the image analysis for detecting malignancy was 100% and the specificity was 87%. The positive predictive value was 91% for detecting malignancy and the negative predictive value was 100%. We conclude that x-ray phase-contrast imaging can accurately detect density variations to obtain information regarding lymph node involvement previously inaccessible with standard absorption x-ray imaging.</p></abstract><funding-group><funding-statement>Financial support is given through Faculties of Science and Health at the University of Copenhagen, through the European Synchrotron Radiation Facility (ESRF), and through the DFG Cluster of Excellence Munich-Center for Advanced Photonics (DFG EXC-158) and the European Research Council (FP7, Starting Grant No. 24012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="5"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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