OSCR

Pitfalls in 2HG Detection With TE-Optimized MRS at 3T.

Overview

Authors: Seyma Alcicek1,2,3,4,5, Dunja Simicic1, Lindsay Blair6,7, Max Saint‐Germain6,7, Helge J. Zöllner1, Christopher W. Davies‐Jenkins1, Matthias Holdhoff6,7, John Laterra6,7, Chetan Bettegowda8, Karisa C. Schreck6,7, Doris D. Lin1,9, Peter B. Barker1,9, David O. Kamson6,7, Georg Oeltzschner1
  1. Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore Maryland USA
  2. Institute of Neuroradiology and Cooperative Brain Imaging Center ‐ CoBIC University Hospital Frankfurt am Main Germany
  3. University Cancer Center Frankfurt (UCT) Frankfurt am Main Germany
  4. German Cancer Research Center (DKFZ) Frankfurt am Main Germany
  5. Frankfurt Cancer Institute (FCI) Frankfurt am Main Germany
  6. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore Maryland USA
  7. Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA
  8. Department of Neurosurgery Johns Hopkins University School of Medicine Baltimore Maryland USA
  9. F. M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute Baltimore Maryland USA
Dates: received 15 January 2026; accepted 28 July 2026; published online 15 September 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1111/jon.70146 · PMID 42742320 · PMCID PMC13576559 · OpenAlex W4409067205
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: structural MRI / diffusion (modality), human (organism), other condition (population), clinical / translational (subfield)
Methods: Statistics, Connectivity, fMRI & imaging
Keywords: biomarker, D‐2‐hydroxyglutarate, isocitrate dehydrogenase mutation, magnetic resonance spectroscopy, oncometabolites
MeSH: Brain Neoplasms*, Glioma*, Glutarates*, Adult, Biomarkers, Tumor, Female, Humans, Isocitrate Dehydrogenase, Magnetic Resonance Spectroscopy, Male, Middle Aged, Reproducibility of Results, Sensitivity and Specificity (* major topic)
Journal subjects: Clinical Investigative Study
Topic: Advanced MRI Techniques and Applications (Radiology, Nuclear Medicine and Imaging, Medicine), according to OpenAlex
Funding: National Institutes of Health (R01 EB035529, R21 EB033516, K99 AG080084, P41 EB031771); Mildred‐Scheel Career Center (Deutsche Krebshilfe)
Citations: not cited yet (Europe PMC); 45 references in the paper

Abstract

Background and Purpose: In vivo 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 nontumor tissue. Therefore, we tested how well TE‐optimized 2HG levels distinguish between IDH‐mutated glioma and nontumor tissue—here, normal‐appearing brain. We further examined the impact of different spectral modeling strategies (baseline stiffness, macromolecule inclusion, and basis set composition).

Methods: Forty‐eight patients with diagnosed/suspected IDH‐mutated glioma were enrolled. 3T MRS data were acquired from tumor and contralateral nontumor tissue with TE‐optimized PRESS and analyzed with “LCModel” software. ROC analysis evaluated 2HG estimates’ ability to distinguish IDH‐mutated glioma from nontumor 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 nontumor tissue with lower sensitivity (range 0.76–0.62) and specificity (0.85–0.78) than the literature suggests for IDH‐mutated versus 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 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.

Conclusions: Spectral overlap with GABA and acetone can lead to false‐positive 2HG detection in nontumor tissue.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

No dataset and no data link were found in the paper.

Data Availability Statement

MRS result tables and statistical analysis code that support the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 3, 28 September 2026

  • Publisher: — → Wiley
  • Authors: added Seyma Alcicek (0000-0002-9447-4906); Lindsay Blair (0000-0001-7335-4537); Helge J. Zöllner (0000-0002-7148-292X); Georg Oeltzschner (0000-0003-3083-9811); removed Seyma Alcicek; Lindsay Blair; Helge J. Zöllner; Georg Oeltzschner

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 5 keywords, 13 MeSH terms, 2 funders, 45 references.

Cite

This paper

Alcicek, S., Simicic, D., Blair, L., Saint‐Germain, M., Zöllner, H. J., Davies‐Jenkins, C. W., Holdhoff, M., Laterra, J., Bettegowda, C., Schreck, K. C., Lin, D. D., Barker, P. B., Kamson, D. O., & Oeltzschner, G. (2026). Pitfalls in 2HG Detection With TE-Optimized MRS at 3T. Journal of neuroimaging : official journal of the American Society of Neuroimaging, 36(5), e70146. https://doi.org/10.1111/jon.70146

BibTeX

@article{alcicek2026pitfalls,
author = {Alcicek, Seyma and Simicic, Dunja and Blair, Lindsay and Saint‐Germain, Max and Zöllner, Helge J. and Davies‐Jenkins, Christopher W. and Holdhoff, Matthias and Laterra, John and Bettegowda, Chetan and Schreck, Karisa C. and Lin, Doris D. and Barker, Peter B. and Kamson, David O. and Oeltzschner, Georg},
title = {{Pitfalls in 2HG Detection With TE-Optimized MRS at 3T}},
journal = {Journal of neuroimaging : official journal of the American Society of Neuroimaging},
year = {2026},
month = sep,
volume = {36},
number = {5},
pages = {e70146},
publisher = {Wiley},
issn = {1051-2284},
doi = {10.1111/jon.70146},
url = {https://doi.org/10.1111/jon.70146},
pmid = {42742320},
pmcid = {PMC13576559}
}

RIS

TY - JOUR
AU - Alcicek, Seyma
AU - Simicic, Dunja
AU - Blair, Lindsay
AU - Saint‐Germain, Max
AU - Zöllner, Helge J.
AU - Davies‐Jenkins, Christopher W.
AU - Holdhoff, Matthias
AU - Laterra, John
AU - Bettegowda, Chetan
AU - Schreck, Karisa C.
AU - Lin, Doris D.
AU - Barker, Peter B.
AU - Kamson, David O.
AU - Oeltzschner, Georg
TI - Pitfalls in 2HG Detection With TE-Optimized MRS at 3T
T2 - Journal of neuroimaging : official journal of the American Society of Neuroimaging
J2 - J Neuroimaging
PY - 2026
DA - 2026/09/01
VL - 36
IS - 5
SP - e70146
SN - 1051-2284
PB - Wiley
DO - 10.1111/jon.70146
UR - https://doi.org/10.1111/jon.70146
LA - en
ER -

CSL-JSON

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