Evidence map›Paper›PMID 40236436›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Pitfalls in 2HG detection with TE-optimized MRS at 3T.

Seyma Alcicek, Dunja Simicic, Lindsay Blair, Max Saint-Germain, Helge J Zöllner, Christopher W Davies-Jenkins, Matthias Holdhoff, John Laterra, Chetan Bettegowda, Karisa C Schreck and 4 more

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Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Seyma AlcicekRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-9447-4906
Dunja SimicicRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lindsay BlairDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-7335-4537
Max Saint-GermainDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Helge J ZöllnerRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-7148-292X
Christopher W Davies-JenkinsRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Matthias HoldhoffDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
John LaterraDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Chetan BettegowdaDepartment of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Karisa C SchreckDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Doris D LinRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Peter B BarkerRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David O KamsonDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Georg OeltzschnerRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-3083-9811

Funding

TRD 4: Platforms for multi-modal and multi-scale imaging dataP41EB031771 · NIBIB · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI Richard Anthony Edward Edden · 2021 to 2026
$9.9M
Model Selection for Magnetic Resonance SpectroscopyR01EB035529 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI Georg Oeltzschner · 2024 to 2026
$1.7M
General Linear Modeling For Magnetic Resonance SpectroscopyR21EB033516 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI OELTZSCHNER, GEORG · 2022 to 2024
$670k
Brain metabolism across the lifespan using multi-parametric MRSK99AG080084 · NIA · JOHNS HOPKINS UNIVERSITY · PI ZOELLNER, HELGE JOERN · 2023 to 2024
$212k
NIA NIH HHS K99 AG080084NIBIB NIH HHS P41 EB031771NIBIB NIH HHS R01 EB035529NIBIB NIH HHS R21 EB033516
6 · The paper itself

Abstract

Background and Purpose: In-vivo magnetic resonance spectroscopy (MRS) of 2-hydroxyglutarate (2HG) may provide diagnostic and monitoring biomarkers in isocitrate dehydrogenase (IDH)-mutated glioma. A previous meta-analysis has shown good diagnostic accuracy of TE-optimized PRESS for IDH-mutated glioma, but most studies feature IDH-wildtype 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 non-tumor tissue. Therefore, we tested how well TE-optimized 2HG levels distinguish between IDH-mutated glioma and non-tumor tissue, in this case, normal-appearing brain. We further examined the impact of different spectral modeling strategies (baseline stiffness, macromolecule inclusion, and basis set composition). Materials and Methods: 48 patients with diagnosed/suspected IDH-mutated glioma were enrolled. 3T MRS data were acquired from tumor and contralateral non-tumor tissue with PRESS localization (TE = 97 ms, optimized for 2HG detection) and analyzed with 'LCModel' software. Receiver operating characteristic analysis evaluated 2HG estimates' ability to distinguish IDH-mutated glioma from non-tumor brain tissue. Modeling interactions between 2HG and other metabolites were evaluated to identify reasons for potential false-positive 2HG detection. Results: TE-optimized PRESS distinguished IDH-mutated glioma from non-tumor tissue with lower sensitivity (range 0.76-0.62) and specificity (0.85-0.78) than literature suggests for IDH-mutated vs. IDH-wildtype glioma. Strong negative correlations between gamma-aminobutyric acid (GABA) and 2HG persisted across all modeling strategies and may lead to false-positive 2HG detection in non-tumor tissue. We further present a cautionary example from a patient on a ketogenic diet, showing that the ketone body acetone can interfere with 2HG detection. Conclusions: Spectral overlap with GABA and acetone can lead to false-positive 2HG detection in non-tumor tissue. Clinicians need to be mindful of these pitfalls when interpreting 2HG estimates.

Identifiers

PMID40236436
PMCPMC11998809

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.