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<title xml:lang="en">Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential</title>
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<name sortKey="Robles, Francisco E" sort="Robles, Francisco E" uniqKey="Robles F" first="Francisco E." last="Robles">Francisco E. Robles</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
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<author>
<name sortKey="Deb, Sanghamitra" sort="Deb, Sanghamitra" uniqKey="Deb S" first="Sanghamitra" last="Deb">Sanghamitra Deb</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wilson, Jesse W" sort="Wilson, Jesse W" uniqKey="Wilson J" first="Jesse W." last="Wilson">Jesse W. Wilson</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
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<name sortKey="Gainey, Christina S" sort="Gainey, Christina S" uniqKey="Gainey C" first="Christina S." last="Gainey">Christina S. Gainey</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
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<author>
<name sortKey="Selim, M Angelica" sort="Selim, M Angelica" uniqKey="Selim M" first="M. Angelica" last="Selim">M. Angelica Selim</name>
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<nlm:aff id="aff2">Department of Pathology, Duke University Medical Center, Durham, NC 27705,
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<name sortKey="Mosca, Paul J" sort="Mosca, Paul J" uniqKey="Mosca P" first="Paul J." last="Mosca">Paul J. Mosca</name>
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<nlm:aff id="aff3">Department of Surgery, Duke University Medical Center, Durham, NC 27705,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
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<name sortKey="Tyler, Douglas S" sort="Tyler, Douglas S" uniqKey="Tyler D" first="Douglas S." last="Tyler">Douglas S. Tyler</name>
<affiliation>
<nlm:aff id="aff4">Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
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<name sortKey="Fischer, Martin C" sort="Fischer, Martin C" uniqKey="Fischer M" first="Martin C." last="Fischer">Martin C. Fischer</name>
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<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
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<name sortKey="Warren, Warren S" sort="Warren, Warren S" uniqKey="Warren W" first="Warren S." last="Warren">Warren S. Warren</name>
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<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
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<title xml:lang="en" level="a" type="main">Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential</title>
<author>
<name sortKey="Robles, Francisco E" sort="Robles, Francisco E" uniqKey="Robles F" first="Francisco E." last="Robles">Francisco E. Robles</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Deb, Sanghamitra" sort="Deb, Sanghamitra" uniqKey="Deb S" first="Sanghamitra" last="Deb">Sanghamitra Deb</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wilson, Jesse W" sort="Wilson, Jesse W" uniqKey="Wilson J" first="Jesse W." last="Wilson">Jesse W. Wilson</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gainey, Christina S" sort="Gainey, Christina S" uniqKey="Gainey C" first="Christina S." last="Gainey">Christina S. Gainey</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Selim, M Angelica" sort="Selim, M Angelica" uniqKey="Selim M" first="M. Angelica" last="Selim">M. Angelica Selim</name>
<affiliation>
<nlm:aff id="aff2">Department of Pathology, Duke University Medical Center, Durham, NC 27705,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mosca, Paul J" sort="Mosca, Paul J" uniqKey="Mosca P" first="Paul J." last="Mosca">Paul J. Mosca</name>
<affiliation>
<nlm:aff id="aff3">Department of Surgery, Duke University Medical Center, Durham, NC 27705,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Tyler, Douglas S" sort="Tyler, Douglas S" uniqKey="Tyler D" first="Douglas S." last="Tyler">Douglas S. Tyler</name>
<affiliation>
<nlm:aff id="aff4">Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fischer, Martin C" sort="Fischer, Martin C" uniqKey="Fischer M" first="Martin C." last="Fischer">Martin C. Fischer</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Warren, Warren S" sort="Warren, Warren S" uniqKey="Warren W" first="Warren S." last="Warren">Warren S. Warren</name>
<affiliation>
<nlm:aff id="aff1">Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</nlm:aff>
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<title level="j">Biomedical Optics Express</title>
<idno type="eISSN">2156-7085</idno>
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<date when="2015">2015</date>
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<div type="abstract" xml:lang="en">
<p>Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pump-probe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct “dusty” quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas.</p>
</div>
</front>
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<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Biomed Opt Express</journal-id>
<journal-id journal-id-type="iso-abbrev">Biomed Opt Express</journal-id>
<journal-id journal-id-type="publisher-id">BOE</journal-id>
<journal-title-group>
<journal-title>Biomedical Optics Express</journal-title>
</journal-title-group>
<issn pub-type="epub">2156-7085</issn>
<publisher>
<publisher-name>Optical Society of America</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26417529</article-id>
<article-id pub-id-type="pmc">4574685</article-id>
<article-id pub-id-type="publisher-id">243707</article-id>
<article-id pub-id-type="doi">10.1364/BOE.6.003631</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Robles</surname>
<given-names>Francisco E.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Deb</surname>
<given-names>Sanghamitra</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wilson</surname>
<given-names>Jesse W.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gainey</surname>
<given-names>Christina S.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Selim</surname>
<given-names>M. Angelica</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mosca</surname>
<given-names>Paul J.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tyler</surname>
<given-names>Douglas S.</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fischer</surname>
<given-names>Martin C.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Warren</surname>
<given-names>Warren S.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
<aff id="aff1">
<label>1</label>
Department of Chemistry, Duke University, Durham, North Carolina 27708,
<country country="US">USA</country>
</aff>
<aff id="aff2">
<label>2</label>
Department of Pathology, Duke University Medical Center, Durham, NC 27705,
<country country="US">USA</country>
</aff>
<aff id="aff3">
<label>3</label>
Department of Surgery, Duke University Medical Center, Durham, NC 27705,
<country country="US">USA</country>
</aff>
<aff id="aff4">
<label>4</label>
Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555,
<country country="US">USA</country>
</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">
<label>*</label>
<email xlink:href="warren.warren@duke.edu">warren.warren@duke.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>27</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection">
<day>01</day>
<month>9</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>27</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>6</volume>
<issue>9</issue>
<fpage>3631</fpage>
<lpage>3645</lpage>
<history>
<date date-type="received">
<day>24</day>
<month>6</month>
<year>2015</year>
</date>
<date date-type="rev-recd">
<day>19</day>
<month>8</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>22</day>
<month>8</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>© 2015 Optical Society of America</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>Optical Society of America</copyright-holder>
</permissions>
<abstract>
<p>Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pump-probe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct “dusty” quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas.</p>
</abstract>
<kwd-group kwd-group-type="OCIS">
<title>OCIS codes: </title>
<kwd>(170.3880) Medical and biological imaging</kwd>
<kwd>(180.5810) Scanning microscopy</kwd>
<kwd>(320.7150) Ultrafast spectroscopy</kwd>
</kwd-group>
<funding-group>
<award-group id="sp1">
<funding-source>Burroughs Wellcome Fund (BWF)
<named-content content-type="doi">10.13039/100000861</named-content>
</funding-source>
<award-id>1012639</award-id>
</award-group>
<award-group id="sp2">
<funding-source>National Institutes of Health (NIH)
<named-content content-type="doi">10.13039/100000002</named-content>
</funding-source>
<award-id>F32CA168497</award-id>
<award-id>F32CA183204</award-id>
<award-id>P41EB015897</award-id>
<award-id>R01-CA166555</award-id>
</award-group>
<award-group id="sp3">
<funding-source>National Science Foundation (NSF)
<named-content content-type="doi">10.13039/100000001</named-content>
</funding-source>
<award-id>CHE-1309017</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
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