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<meta name="citation_funding_source" content="citation_funder_id=https://doi.org/10.13039/100000002;citation_grant_number=R01 CA213158;citation_grant_number=R01 CA264992;citation_grant_number=U01 CA176110;" />
<meta name="citation_funding_source" content="citation_funder_id=https://doi.org/10.13039/100004917;citation_grant_number=RR220038;" />
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<meta name="type" content="article" />
<meta name="category" content="research-article" />
<meta name="HW.identifier" content="/ajnr/45/10/1545.atom" />
<meta name="HW.pisa" content="ajnr;45/10/1545" />
<meta name="DC.Format" content="text/html" />
<meta name="DC.Language" content="en" />
<meta name="DC.Title" content="Identification of a Single-Dose, Low-Flip-Angle–Based CBV Threshold for Fractional Tumor Burden Mapping in Recurrent Glioblastoma" />
<meta name="DC.Identifier" content="10.3174/ajnr.A8357" />
<meta name="DC.Date" content="2024-10-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2024 by American Journal of Neuroradiology" />
<meta name="DC.AccessRights" content="restricted" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol. This study aimed to identify the rCBV thresholds for the LFA protocol that generate the most accurate FTB maps, concordant with those obtained from the reference MFA protocol.

MATERIALS AND METHODS: Fifty-two patients with grade-IV glioblastoma who had prior surgical resection and received chemotherapy and radiation therapy were included in the study. Two sets of DSC-MR imaging data were collected sequentially first by using LFA protocol with no preload, which served as the preload for the subsequent MFA protocol. Standardized relative CBV maps (sRCBV) were obtained for each patient and coregistered with the anatomic postcontrast T1-weighted images. The reference MFA-based FTB maps were computed by using previously published sRCBV thresholds (1.0 and 1.56). A receiver operating characteristics (ROC) analysis was conducted to identify the optimal, voxelwise LFA sRCBV thresholds, and the sensitivity, specificity, and accuracy of the LFA-based FTB maps were computed with respect to the MFA-based reference.

RESULTS: The mean sRCBV values of tumors across patients exhibited strong agreement (concordance correlation coefficient = 0.99) between the 2 protocols. Using the ROC analysis, the optimal lower LFA threshold that accurately distinguishes PTRE from tumor recurrence was found to be 1.0 (sensitivity: 87.77%; specificity: 90.22%), equivalent to the ground truth. To identify aggressive tumor regions, the ROC analysis identified an upper LFA threshold of 1.37 (sensitivity: 90.87%; specificity: 91.10%) for the reference MFA threshold of 1.56.

CONCLUSIONS: For LFA-based FTB maps, an sRCBV threshold of 1.0 and 1.37 can differentiate PTRE from recurrent tumors. FTB maps aid in surgical planning, guiding pathologic diagnosis and treatment strategies in the recurrent setting. This study further confirms the reliability of single-dose LFA-based DSC-MR imaging.

CCC
:   concordance correlation coefficient
FTB
:   fractional tumor burden
LFA
:   low flip angle
MFA
:   moderate flip angle
PTRE
:   posttreatment radiation effects
rCBV
:   relative cerebral blood volume
ROC
:   receiver operating characteristic
sRCBV
:   standardized relative CBV
WHO
:   World Health Organization" />
<meta name="DC.Contributor" content="Aliya Anil" />
<meta name="DC.Contributor" content="Ashley M. Stokes" />
<meta name="DC.Contributor" content="John P. Karis" />
<meta name="DC.Contributor" content="Laura C. Bell" />
<meta name="DC.Contributor" content="Jennifer Eschbacher" />
<meta name="DC.Contributor" content="Kristofer Jennings" />
<meta name="DC.Contributor" content="Melissa A. Prah" />
<meta name="DC.Contributor" content="Leland S. Hu" />
<meta name="DC.Contributor" content="Jerrold L. Boxerman" />
<meta name="DC.Contributor" content="Kathleen M. Schmainda" />
<meta name="DC.Contributor" content="C. Chad Quarles" />
<meta name="article:published_time" content="2024-10-01" />
<meta name="article:section" content="Brain Tumor Imaging" />
<meta name="citation_title" content="Identification of a Single-Dose, Low-Flip-Angle–Based CBV Threshold for Fractional Tumor Burden Mapping in Recurrent Glioblastoma" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol. This study aimed to identify the rCBV thresholds for the LFA protocol that generate the most accurate FTB maps, concordant with those obtained from the reference MFA protocol.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Fifty-two patients with grade-IV glioblastoma who had prior surgical resection and received chemotherapy and radiation therapy were included in the study. Two sets of DSC-MR imaging data were collected sequentially first by using LFA protocol with no preload, which served as the preload for the subsequent MFA protocol. Standardized relative CBV maps (sRCBV) were obtained for each patient and coregistered with the anatomic postcontrast T1-weighted images. The reference MFA-based FTB maps were computed by using previously published sRCBV thresholds (1.0 and 1.56). A receiver operating characteristics (ROC) analysis was conducted to identify the optimal, voxelwise LFA sRCBV thresholds, and the sensitivity, specificity, and accuracy of the LFA-based FTB maps were computed with respect to the MFA-based reference.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;The mean sRCBV values of tumors across patients exhibited strong agreement (concordance correlation coefficient = 0.99) between the 2 protocols. Using the ROC analysis, the optimal lower LFA threshold that accurately distinguishes PTRE from tumor recurrence was found to be 1.0 (sensitivity: 87.77%; specificity: 90.22%), equivalent to the ground truth. To identify aggressive tumor regions, the ROC analysis identified an upper LFA threshold of 1.37 (sensitivity: 90.87%; specificity: 91.10%) for the reference MFA threshold of 1.56.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;For LFA-based FTB maps, an sRCBV threshold of 1.0 and 1.37 can differentiate PTRE from recurrent tumors. FTB maps aid in surgical planning, guiding pathologic diagnosis and treatment strategies in the recurrent setting. This study further confirms the reliability of single-dose LFA-based DSC-MR imaging.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
<meta name="citation_publisher" content="American Journal of Neuroradiology" />
<meta name="citation_publication_date" content="2024/10/01" />
<meta name="citation_mjid" content="ajnr;45/10/1545" />
<meta name="citation_id" content="45/10/1545" />
<meta name="citation_public_url" content="http://ajnr-stage2.stage.highwire.org/content/45/10/1545" />
<meta name="citation_abstract_html_url" content="http://ajnr-stage2.stage.highwire.org/content/45/10/1545.abstract" />
<meta name="citation_full_html_url" content="http://ajnr-stage2.stage.highwire.org/content/45/10/1545.full" />
<meta name="citation_pdf_url" content="http://ajnr-stage2.stage.highwire.org/content/ajnr/45/10/1545.full.pdf" />
<meta name="citation_issn" content="0195-6108" />
<meta name="citation_issn" content="1936-959X" />
<meta name="citation_doi" content="10.3174/ajnr.A8357" />
<meta name="citation_pmid" content="38782593" />
<meta name="citation_volume" content="45" />
<meta name="citation_issue" content="10" />
<meta name="citation_article_type" content="Research Article" />
<meta name="citation_section" content="Brain Tumor Imaging" />
<meta name="citation_firstpage" content="1545" />
<meta name="citation_lastpage" content="1551" />
<meta name="citation_author" content="Aliya Anil" />
<meta name="citation_author_institution" content="aFrom the Cancer System Imaging (A.A., C.C.Q.), The University of Texas MD Anderson Cancer Center, Houston, Texas" />
<meta name="citation_author_orcid" content="https://orcid.org/0009-0009-6050-1820" />
<meta name="citation_author" content="Ashley M. Stokes" />
<meta name="citation_author_institution" content="bDivision of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Barrow Neurological Institute, Phoenix, Arizona" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0003-1137-5003" />
<meta name="citation_author" content="John P. Karis" />
<meta name="citation_author_institution" content="cDepartment of Neuroradiology (J.P.K.), Barrow Neurological Institute, Phoenix, Arizona" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0003-4181-4185" />
<meta name="citation_author" content="Laura C. Bell" />
<meta name="citation_author_institution" content="dClinical Imaging Group (L.C.B.), Genentech Inc., San Francisco, California" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0001-8164-8324" />
<meta name="citation_author" content="Jennifer Eschbacher" />
<meta name="citation_author_institution" content="eDepartment of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-2599-0819" />
<meta name="citation_author" content="Kristofer Jennings" />
<meta name="citation_author_institution" content="fDepartment of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-5442-9326" />
<meta name="citation_author" content="Melissa A. Prah" />
<meta name="citation_author_institution" content="gDepartment of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0001-9775-9926" />
<meta name="citation_author" content="Leland S. Hu" />
<meta name="citation_author_institution" content="hDepartment of Radiology (L.S.H.), Division of Neuroradiology, Mayo Clinic Arizona, Phoenix, Arizona" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0001-9282-7619" />
<meta name="citation_author" content="Jerrold L. Boxerman" />
<meta name="citation_author_institution" content="iDepartment of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-0594-1542" />
<meta name="citation_author" content="Kathleen M. Schmainda" />
<meta name="citation_author_institution" content="gDepartment of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0001-6402-2602" />
<meta name="citation_author" content="C. Chad Quarles" />
<meta name="citation_author_institution" content="aFrom the Cancer System Imaging (A.A., C.C.Q.), The University of Texas MD Anderson Cancer Center, Houston, Texas" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-1731-0940" />
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<meta name="twitter:title" content="Identification of a Single-Dose, Low-Flip-Angle–Based CBV Threshold for Fractional Tumor Burden Mapping in Recurrent Glioblastoma" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol. This study aimed to identify the rCBV thresholds for the LFA protocol that generate the most accurate FTB maps, concordant with those obtained from the reference MFA protocol.

MATERIALS AND METHODS: Fifty-two patients with grade-IV glioblastoma who had prior surgical resection and received chemotherapy and radiation therapy were included in the study. Two sets of DSC-MR imaging data were collected sequentially first by using LFA protocol with no preload, which served as the preload for the subsequent MFA protocol. Standardized relative CBV maps (sRCBV) were obtained for each patient and coregistered with the anatomic postcontrast T1-weighted images. The reference MFA-based FTB maps were computed by using previously published sRCBV thresholds (1.0 and 1.56). A receiver operating characteristics (ROC) analysis was conducted to identify the optimal, voxelwise LFA sRCBV thresholds, and the sensitivity, specificity, and accuracy of the LFA-based FTB maps were computed with respect to the MFA-based reference.

RESULTS: The mean sRCBV values of tumors across patients exhibited strong agreement (concordance correlation coefficient = 0.99) between the 2 protocols. Using the ROC analysis, the optimal lower LFA threshold that accurately distinguishes PTRE from tumor recurrence was found to be 1.0 (sensitivity: 87.77%; specificity: 90.22%), equivalent to the ground truth. To identify aggressive tumor regions, the ROC analysis identified an upper LFA threshold of 1.37 (sensitivity: 90.87%; specificity: 91.10%) for the reference MFA threshold of 1.56.

CONCLUSIONS: For LFA-based FTB maps, an sRCBV threshold of 1.0 and 1.37 can differentiate PTRE from recurrent tumors. FTB maps aid in surgical planning, guiding pathologic diagnosis and treatment strategies in the recurrent setting. This study further confirms the reliability of single-dose LFA-based DSC-MR imaging.

CCC
:   concordance correlation coefficient
FTB
:   fractional tumor burden
LFA
:   low flip angle
MFA
:   moderate flip angle
PTRE
:   posttreatment radiation effects
rCBV
:   relative cerebral blood volume
ROC
:   receiver operating characteristic
sRCBV
:   standardized relative CBV
WHO
:   World Health Organization" />
<meta name="og-title" property="og:title" content="Identification of a Single-Dose, Low-Flip-Angle–Based CBV Threshold for Fractional Tumor Burden Mapping in Recurrent Glioblastoma" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/45/10/1545" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol. This study aimed to identify the rCBV thresholds for the LFA protocol that generate the most accurate FTB maps, concordant with those obtained from the reference MFA protocol.

MATERIALS AND METHODS: Fifty-two patients with grade-IV glioblastoma who had prior surgical resection and received chemotherapy and radiation therapy were included in the study. Two sets of DSC-MR imaging data were collected sequentially first by using LFA protocol with no preload, which served as the preload for the subsequent MFA protocol. Standardized relative CBV maps (sRCBV) were obtained for each patient and coregistered with the anatomic postcontrast T1-weighted images. The reference MFA-based FTB maps were computed by using previously published sRCBV thresholds (1.0 and 1.56). A receiver operating characteristics (ROC) analysis was conducted to identify the optimal, voxelwise LFA sRCBV thresholds, and the sensitivity, specificity, and accuracy of the LFA-based FTB maps were computed with respect to the MFA-based reference.

RESULTS: The mean sRCBV values of tumors across patients exhibited strong agreement (concordance correlation coefficient = 0.99) between the 2 protocols. Using the ROC analysis, the optimal lower LFA threshold that accurately distinguishes PTRE from tumor recurrence was found to be 1.0 (sensitivity: 87.77%; specificity: 90.22%), equivalent to the ground truth. To identify aggressive tumor regions, the ROC analysis identified an upper LFA threshold of 1.37 (sensitivity: 90.87%; specificity: 91.10%) for the reference MFA threshold of 1.56.

CONCLUSIONS: For LFA-based FTB maps, an sRCBV threshold of 1.0 and 1.37 can differentiate PTRE from recurrent tumors. FTB maps aid in surgical planning, guiding pathologic diagnosis and treatment strategies in the recurrent setting. This study further confirms the reliability of single-dose LFA-based DSC-MR imaging.

CCC
:   concordance correlation coefficient
FTB
:   fractional tumor burden
LFA
:   low flip angle
MFA
:   moderate flip angle
PTRE
:   posttreatment radiation effects
rCBV
:   relative cerebral blood volume
ROC
:   receiver operating characteristic
sRCBV
:   standardized relative CBV
WHO
:   World Health Organization" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node110806--5" data-node-nid="110806" id="top-node-110806--6947674225" data-pisa="ajnr;45/10/1545" data-pisa-master="ajnr;ajnr.A8357" data-apath="/ajnr/45/10/1545.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Brain Tumor Imaging</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Identification of a Single-Dose, Low-Flip-Angle–Based CBV Threshold for Fractional Tumor Burden Mapping in Recurrent Glioblastoma</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">Aliya Anil</span>, <span class="highwire-citation-author" data-delta="1">Ashley M. Stokes</span>, <span class="highwire-citation-author" data-delta="2">John P. Karis</span>, <span class="highwire-citation-author" data-delta="3">Laura C. Bell</span>, <span class="highwire-citation-author" data-delta="4">Jennifer Eschbacher</span>, <span class="highwire-citation-author" data-delta="5">Kristofer Jennings</span>, <span class="highwire-citation-author" data-delta="6">Melissa A. Prah</span>, <span class="highwire-citation-author" data-delta="7">Leland S. Hu</span>, <span class="highwire-citation-author" data-delta="8">Jerrold L. Boxerman</span>, <span class="highwire-citation-author" data-delta="9">Kathleen M. Schmainda</span> and <span class="highwire-citation-author" data-delta="10">C. Chad Quarles</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">October 2024,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(10) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1545-1551; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A8357 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-110806--6947674225" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Aliya Anil </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Cancer System Imaging (A.A., C.C.Q.), The University of Texas MD Anderson Cancer Center, Houston, Texas</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Aliya%2BAnil%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Anil%20A&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AAliya%2BAnil%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0009-0009-6050-1820" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Aliya Anil</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Ashley M. Stokes </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Barrow Neurological Institute, Phoenix, Arizona</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Ashley%2BM.%2BStokes%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Stokes%20AM&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AAshley%2BM.%2BStokes%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-1137-5003" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Ashley M. Stokes</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">John P. Karis </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Department of Neuroradiology (J.P.K.), Barrow Neurological Institute, Phoenix, Arizona</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=John%2BP.%2BKaris%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Karis%20JP&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AJohn%2BP.%2BKaris%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-4181-4185" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for John P. Karis</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">Laura C. Bell </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Clinical Imaging Group (L.C.B.), Genentech Inc., San Francisco, California</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Laura%2BC.%2BBell%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Bell%20LC&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ALaura%2BC.%2BBell%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-8164-8324" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Laura C. Bell</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Jennifer Eschbacher </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>e</span>Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Jennifer%2BEschbacher%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Eschbacher%20J&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AJennifer%2BEschbacher%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-2599-0819" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Jennifer Eschbacher</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">Kristofer Jennings </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>f</span>Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Kristofer%2BJennings%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Jennings%20K&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AKristofer%2BJennings%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-5442-9326" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Kristofer Jennings</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">Melissa A. Prah </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>g</span>Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Melissa%2BA.%2BPrah%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Prah%20MA&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AMelissa%2BA.%2BPrah%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-9775-9926" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Melissa A. 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Hu </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>h</span>Department of Radiology (L.S.H.), Division of Neuroradiology, Mayo Clinic Arizona, Phoenix, Arizona</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Leland%2BS.%2BHu%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Hu%20LS&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ALeland%2BS.%2BHu%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-9282-7619" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Leland S. Hu</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">Jerrold L. Boxerman </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>i</span>Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Jerrold%2BL.%2BBoxerman%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Boxerman%20JL&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AJerrold%2BL.%2BBoxerman%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-0594-1542" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Jerrold L. 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Schmainda </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>g</span>Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Kathleen%2BM.%2BSchmainda%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Schmainda%20KM&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AKathleen%2BM.%2BSchmainda%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-6402-2602" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Kathleen M. 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Chad Quarles </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Cancer System Imaging (A.A., C.C.Q.), The University of Texas MD Anderson Cancer Center, Houston, Texas</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=C.%2BChad%2BQuarles%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Quarles%20CC&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AC.%2BChad%2BQuarles%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-1731-0940" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. 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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><div id="sec-1" class="subsection"><p id="p-1"><strong>BACKGROUND AND PURPOSE:</strong> DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol. This study aimed to identify the rCBV thresholds for the LFA protocol that generate the most accurate FTB maps, concordant with those obtained from the reference MFA protocol.</p></div><div id="sec-2" class="subsection"><p id="p-2"><strong>MATERIALS AND METHODS:</strong> Fifty-two patients with grade-IV glioblastoma who had prior surgical resection and received chemotherapy and radiation therapy were included in the study. Two sets of DSC-MR imaging data were collected sequentially first by using LFA protocol with no preload, which served as the preload for the subsequent MFA protocol. Standardized relative CBV maps (sRCBV) were obtained for each patient and coregistered with the anatomic postcontrast T1-weighted images. The reference MFA-based FTB maps were computed by using previously published sRCBV thresholds (1.0 and 1.56). A receiver operating characteristics (ROC) analysis was conducted to identify the optimal, voxelwise LFA sRCBV thresholds, and the sensitivity, specificity, and accuracy of the LFA-based FTB maps were computed with respect to the MFA-based reference.</p></div><div id="sec-3" class="subsection"><p id="p-3"><strong>RESULTS:</strong> The mean sRCBV values of tumors across patients exhibited strong agreement (concordance correlation coefficient = 0.99) between the 2 protocols. Using the ROC analysis, the optimal lower LFA threshold that accurately distinguishes PTRE from tumor recurrence was found to be 1.0 (sensitivity: 87.77%; specificity: 90.22%), equivalent to the ground truth. To identify aggressive tumor regions, the ROC analysis identified an upper LFA threshold of 1.37 (sensitivity: 90.87%; specificity: 91.10%) for the reference MFA threshold of 1.56.</p></div><div id="sec-4" class="subsection"><p id="p-4"><strong>CONCLUSIONS:</strong> For LFA-based FTB maps, an sRCBV threshold of 1.0 and 1.37 can differentiate PTRE from recurrent tumors. FTB maps aid in surgical planning, guiding pathologic diagnosis and treatment strategies in the recurrent setting. This study further confirms the reliability of single-dose LFA-based DSC-MR imaging.</p></div></div><div class="section glossary" id="glossary-1"><h2 class="">ABBREVIATIONS:</h2><dl id="def-list-1"><dt id="def-item-1">CCC<span class="def-item-dt-sep"></span></dt><dd>concordance correlation coefficient<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">FTB<span class="def-item-dt-sep"></span></dt><dd>fractional tumor burden<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">LFA<span class="def-item-dt-sep"></span></dt><dd>low flip angle<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">MFA<span class="def-item-dt-sep"></span></dt><dd>moderate flip angle<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">PTRE<span class="def-item-dt-sep"></span></dt><dd>posttreatment radiation effects<span class="def-item-dd-sep"></span></dd><dt id="def-item-6">rCBV<span class="def-item-dt-sep"></span></dt><dd>relative cerebral blood volume<span class="def-item-dd-sep"></span></dd><dt id="def-item-7">ROC<span class="def-item-dt-sep"></span></dt><dd>receiver operating characteristic<span class="def-item-dd-sep"></span></dd><dt id="def-item-8">sRCBV<span class="def-item-dt-sep"></span></dt><dd>standardized relative CBV<span class="def-item-dd-sep"></span></dd><dt id="def-item-9">WHO<span class="def-item-dt-sep"></span></dt><dd>World Health Organization</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2024 by American Journal of Neuroradiology</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/45/10/1545.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 45</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 10 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Oct 2024 </div></div>
      
      
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      <div class="highwire-cite-title">Identification of a Single-Dose, Low-Flip-Angle–Based CBV Threshold for Fractional Tumor Burden Mapping in Recurrent Glioblastoma</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Aliya</span> <span class="nlm-surname">Anil</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Ashley M.</span> <span class="nlm-surname">Stokes</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">John P.</span> <span class="nlm-surname">Karis</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Laura C.</span> <span class="nlm-surname">Bell</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Jennifer</span> <span class="nlm-surname">Eschbacher</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Kristofer</span> <span class="nlm-surname">Jennings</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Melissa A.</span> <span class="nlm-surname">Prah</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Leland S.</span> <span class="nlm-surname">Hu</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Jerrold L.</span> <span class="nlm-surname">Boxerman</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Kathleen M.</span> <span class="nlm-surname">Schmainda</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">C. Chad</span> <span class="nlm-surname">Quarles</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Oct 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(10) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1545-1551; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8357 </span></div>
  
  
  
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      <div class="highwire-cite-title">Identification of a Single-Dose, Low-Flip-Angle–Based CBV Threshold for Fractional Tumor Burden Mapping in Recurrent Glioblastoma</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Aliya</span> <span class="nlm-surname">Anil</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Ashley M.</span> <span class="nlm-surname">Stokes</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">John P.</span> <span class="nlm-surname">Karis</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Laura C.</span> <span class="nlm-surname">Bell</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Jennifer</span> <span class="nlm-surname">Eschbacher</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Kristofer</span> <span class="nlm-surname">Jennings</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Melissa A.</span> <span class="nlm-surname">Prah</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Leland S.</span> <span class="nlm-surname">Hu</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Jerrold L.</span> <span class="nlm-surname">Boxerman</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Kathleen M.</span> <span class="nlm-surname">Schmainda</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">C. Chad</span> <span class="nlm-surname">Quarles</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Oct 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(10) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1545-1551; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8357 </span></div>
  
  
  
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