{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:42:00Z","timestamp":1789486920187,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EB035529"],"award-info":[{"award-number":["R01 EB035529"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 EB033516"],"award-info":[{"award-number":["R21 EB033516"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99 AG080084"],"award-info":[{"award-number":["K99 AG080084"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41 EB031771"],"award-info":[{"award-number":["P41 EB031771"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuroimaging"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>In vivo MRS of 2\u2010hydroxyglutarate (2HG) may provide diagnostic and monitoring biomarkers in isocitrate dehydrogenase (IDH)\u2010mutated glioma. A previous meta\u2010analysis has shown good diagnostic accuracy of TE\u2010optimized PRESS for IDH\u2010mutated glioma, but most studies feature IDH\u2010wildtype glioma as a comparison. However, when considering newly identified brain lesions that may mimic glioma, full characterization of its diagnostic utility should also consider the accuracy of 2HG measurement in nontumor tissue. Therefore, we tested how well TE\u2010optimized 2HG levels distinguish between IDH\u2010mutated glioma and nontumor tissue\u2014here, normal\u2010appearing brain. We further examined the impact of different spectral modeling strategies (baseline stiffness, macromolecule inclusion, and basis set composition).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty\u2010eight patients with diagnosed\/suspected IDH\u2010mutated glioma were enrolled. 3T MRS data were acquired from tumor and contralateral nontumor tissue with TE\u2010optimized PRESS and analyzed with \u201cLCModel\u201d software. ROC analysis evaluated 2HG estimates\u2019 ability to distinguish IDH\u2010mutated glioma from nontumor tissue. Modeling interactions between 2HG and other metabolites were evaluated to identify reasons for potential false\u2010positive 2HG detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TE\u2010optimized PRESS distinguished IDH\u2010mutated glioma from nontumor tissue with lower sensitivity (range 0.76\u20130.62) and specificity (0.85\u20130.78) than the literature suggests for IDH\u2010mutated versus IDH\u2010wildtype glioma. Strong negative correlations between gamma\u2010aminobutyric acid (GABA) and 2HG persisted across all modeling strategies and may lead to false\u2010positive 2HG detection in nontumor tissue. We further present a cautionary example from a patient on a ketogenic diet, showing that ketone body acetone can interfere with 2HG detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Spectral overlap with GABA and acetone can lead to false\u2010positive 2HG detection in nontumor tissue.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jon.70146","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:34:26Z","timestamp":1789479266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pitfalls in 2HG Detection With TE\u2010Optimized MRS at 3T"],"prefix":"10.1111","volume":"36","author":[{"given":"Seyma","family":"Alcicek","sequence":"first","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Institute of Neuroradiology and Cooperative Brain Imaging Center \u2010 CoBIC University Hospital Frankfurt am Main Germany"},{"name":"University Cancer Center Frankfurt (UCT)  Frankfurt am Main Germany"},{"name":"German Cancer Research Center (DKFZ) Frankfurt am Main Germany"},{"name":"Frankfurt Cancer Institute (FCI) Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Simicic","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Saint\u2010Germain","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge J.","family":"Z\u00f6llner","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Davies\u2010Jenkins","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Holdhoff","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Laterra","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan","family":"Bettegowda","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karisa C.","family":"Schreck","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris D.","family":"Lin","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Barker","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. 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