APT and GluCEST imaging at 5.0 T in patients with brain tumors: a phantom reproducibility validation and clinical study

APT and GluCEST imaging at 5.0 T in patients with brain tumors: a phantom reproducibility validation and clinical study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article APT and GluCEST imaging at 5.0 T in patients with brain tumors: a phantom reproducibility validation and clinical study Tong Chen, Ling Wang, Tianjun Wang, Chao Zheng, Zhiwei Qin, Wu Cai, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9346131/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Purpose: To evaluate the reproducibility of amide proton transfer (APT) and glutamate chemical exchange saturation transfer (GluCEST) imaging at 5 T and to investigate their feasibility and clinical value in patients with brain tumors. Methods: Phantom experiments under varying pH conditions and bovine serum albumin (BSA) concentrations were performed to assess the within-session, between-session, and between-day reproducibility of amide proton transfer (APT) and glutamate chemical exchange saturation transfer (GluCEST) measurements using intraclass correlation coefficients (ICCs) and coefficients of variation (CVs). In vivo APT and GluCEST imaging was performed in 96 patients with brain tumors. Intra- and inter-observer agreement of APTmean and Glumean measurements was evaluated using ICCs and Bland–Altman analysis across tumor, peritumoral edema, and normal brain tissue regions. Quantitative tumor-region APT and GluCEST metrics (APT/Glumean, APT/Glu difference, and APT/Glu change ratio) were compared among major tumor subtypes using the Kruskal-Wallis test, followed by Bonferroni-corrected pairwise comparisons. Results: In phantom studies, both APT and GluCEST demonstrated excellent reproducibility across all experimental conditions, with ICCs consistently exceeding 0.96 and most CVs below 5%. Both contrasts showed clear pH- and concentration-dependent signal changes, with GluCEST exhibiting greater sensitivity to pH variations than APT. In patients, intra- and inter-observer agreement for APTmean and Glumean was high across tumor, peritumoral edema, and normal brain regions (ICCs > 0.93). APT and GluCEST values in tumor and peritumoral edema regions were significantly higher than those in normal brain tissue (p < 0.05) and significant subtype-related differences were observed in tumor regions. After multiple-comparison correction, GluCEST-derived difference and change ratio remained significantly different between high-grade and low-grade gliomas, whereas most APT-derived differences did not. Conclusion: APT and GluCEST imaging at 5 T are reproducible and clinically feasible. GluCEST demonstrates greater sensitivity to glioma-related biochemical differences and shows promise as a complementary imaging biomarker for glioma grading and brain tumor characterization. Reproducibility 5T APT Glu Brain tumors Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterial.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 04 May, 2026 Reviews received at journal 04 May, 2026 Reviews received at journal 27 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviews received at journal 23 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers invited by journal 21 Apr, 2026 Editor assigned by journal 21 Apr, 2026 Editor invited by journal 10 Apr, 2026 Submission checks completed at journal 09 Apr, 2026 First submitted to journal 09 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9346131","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":630648653,"identity":"9a625502-c497-4fff-ac09-5403b33c1ff5","order_by":0,"name":"Tong Chen","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Tong","middleName":"","lastName":"Chen","suffix":""},{"id":630648658,"identity":"b21da6a4-4323-4e51-a54d-432f91def741","order_by":1,"name":"Ling Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow 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study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Reproducibility, 5T, APT, Glu, Brain tumors","lastPublishedDoi":"10.21203/rs.3.rs-9346131/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9346131/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e To evaluate the reproducibility of amide proton transfer (APT) and glutamate chemical exchange saturation transfer (GluCEST) imaging at 5 T and to investigate their feasibility and clinical value in patients with brain tumors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003ePhantom experiments under varying pH conditions and bovine serum albumin (BSA) concentrations were performed to assess the within-session, between-session, and between-day reproducibility of amide proton transfer (APT) and glutamate chemical exchange saturation transfer (GluCEST) measurements using intraclass correlation coefficients (ICCs) and coefficients of variation (CVs). In vivo APT and GluCEST imaging was performed in 96 patients with brain tumors. Intra- and inter-observer agreement of APTmean and Glumean measurements was evaluated using ICCs and Bland–Altman analysis across tumor, peritumoral edema, and normal brain tissue regions. Quantitative tumor-region APT and GluCEST metrics (APT/Glumean, APT/Glu difference, and APT/Glu change ratio) were compared among major tumor subtypes using the Kruskal-Wallis test, followed by Bonferroni-corrected pairwise comparisons.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In phantom studies, both APT and GluCEST demonstrated excellent reproducibility across all experimental conditions, with ICCs consistently exceeding 0.96 and most CVs below 5%. Both contrasts showed clear pH- and concentration-dependent signal changes, with GluCEST exhibiting greater sensitivity to pH variations than APT. In patients, intra- and inter-observer agreement for APTmean and Glumean was high across tumor, peritumoral edema, and normal brain regions (ICCs \u0026gt; 0.93). APT and GluCEST values in tumor and peritumoral edema regions were significantly higher than those in normal brain tissue (p \u0026lt; 0.05) and significant subtype-related differences were observed in tumor regions. After multiple-comparison correction, GluCEST-derived difference and change ratio remained significantly different between high-grade and low-grade gliomas, whereas most APT-derived differences did not.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e APT and GluCEST imaging at 5 T are reproducible and clinically feasible. GluCEST demonstrates greater sensitivity to glioma-related biochemical differences and shows promise as a complementary imaging biomarker for glioma grading and brain tumor characterization.\u003c/p\u003e","manuscriptTitle":"APT and GluCEST imaging at 5.0 T in patients with brain tumors: a phantom reproducibility validation and clinical study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-02 18:50:50","doi":"10.21203/rs.3.rs-9346131/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-05T03:54:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T13:07:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-28T00:02:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188887190593261402974533761937719973010","date":"2026-04-24T03:07:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303937564647209927951851329411598252238","date":"2026-04-23T20:03:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T12:58:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276073058550384328131475220632322449778","date":"2026-04-23T04:37:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135772204513589360580539063279787444421","date":"2026-04-22T13:02:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98400928285948257349614009732148079902","date":"2026-04-22T09:40:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-22T03:04:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-22T02:53:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-10T04:13:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-09T14:46:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Imaging","date":"2026-04-09T13:40:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a988154e-6f59-4d5e-94bb-440e1f2d5f2c","owner":[],"postedDate":"May 2nd, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-05T03:54:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T13:07:31+00:00","index":72,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-16T12:08:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-02 18:50:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9346131","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9346131","identity":"rs-9346131","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}