Evidence map›Paper›PMID 41964041›Full record

ArticleMagnetic resonance in medicine2026

The Impact and Reliability of Tissue Segmentation on In Vivo Magnetic Resonance Spectroscopy Metabolite Quantification.

Jessica Archibald, Kay Chioma Igwe, Antonia Kaiser, Karl Landheer, Jaimie Lee, John L K Kramer, Aaron T Gudmundson, Helge J Zöllner, Georg Oeltzschner, Candace C Fleischer and 3 more

Abstract read
In one paragraph

Article in Magnetic resonance in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Jessica ArchibaldDepartment of Radiology, Weill Cornell Medicine, New York, New York, USA.ORCID https://orcid.org/0000-0001-6651-183X
Kay Chioma IgweDepartment of Biomedical Engineering, Columbia University Fu Foundation School of Engineering and Applied Science, New York, New York, USA.ORCID https://orcid.org/0000-0002-9909-9930
Antonia KaiserCIBM Center for Biomedical Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Karl LandheerRegeneron Genetics Center, Tarrytown, New York, USA.ORCID https://orcid.org/0000-0001-5012-3007
Jaimie LeeDepartment of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.ORCID https://orcid.org/0009-0009-6246-2773
John L K KramerDepartment of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Aaron T GudmundsonThe Malone Center for Engineering in Healthcare, Johns Hopkins University, Baltimore, Maryland, USA.ORCID https://orcid.org/0000-0001-5104-0959
Helge J ZöllnerRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID https://orcid.org/0000-0002-7148-292X
Georg OeltzschnerRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID https://orcid.org/0000-0003-3083-9811
Candace C FleischerDepartment of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.ORCID https://orcid.org/0000-0003-3265-2276
Niklaus ZölchInstitute of Forensic Medicine, Universität Zürich, Zürich, Switzerland.
Jamie NearSunnybrook Research Institute and University of Toronto, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0003-3516-936X
Mark MikkelsenDepartment of Radiology, Weill Cornell Medicine, New York, New York, USA.ORCID https://orcid.org/0000-0002-0349-3782

Funding

A novel framework for quantifying metabolic brain healthDP2NS127704 · NINDS · EMORY UNIVERSITY · PI FLEISCHER, CANDACE C. · 2021 to 2024
$2.3M
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
Optimized Multi-Metabolite Edited MRS at 3TK99EB028828 · NIBIB · WEILL MEDICAL COLL OF CORNELL UNIV · PI MIKKELSEN, MARK · 2020 to 2021
$169k
NIBIB NIH HHS K99 EB028828NIH HHS DP2NS127704NIH HHS K99AG080084NIH HHS K99EB028828NIH HHS R01EB035529NIH HHS R21EB033516
6 · The paper itself

Abstract

purposeQuantification of metabolite concentrations using MRS requires tissue-dependent signal corrections. Accurate estimation of voxel tissue composition is therefore essential. Commonly used brain tissue segmentation tools differ in their algorithms and implementation, potentially introducing variability in MRS-derived concentration estimates. This study investigates the impact and reliability of tissue segmentation on metabolite quantification.

methodsThree segmentation tools (ANTs, FSL, SPM) were evaluated using an in vivo test-retest MRI/MRS dataset. Voxelwise GM/WM/CSF fractions were applied to compute tissue-corrected total creatine (tCr) concentrations. Linear mixed-effects modeling, variance-component partitioning, and intraclass correlation coefficients (ICCs) quantified tool-, session-, and participant-related variance under permutation scenarios that isolated segmentation- and MRS-related effects. As a benchmark for segmentation performance, comparisons with manually segmented data were conducted across three brain regions.

resultsSegmentation tools produced systematically different tissue fractions that propagated into differences in tCr concentration estimates. Variance partitioning attributed 56.8%, 50.0%, and 51.3% of total tCr concentration variability to segmentation tool across the three permutations, with participant-specific factors accounting for 34.7%, 36.2%, and 28.5%, respectively. When segmentation variability was held constant, test-retest reliability was high (ICC > 0.8) but dropped to ∼0.5 when both segmentation and MRS variability varied. Agreement with manual segmentation was region- and tool-dependent, with the lowest agreement in the thalamus.

conclusionTissue segmentation contributes substantially to the variability in MRS-derived metabolite concentration estimates. These results underscore the need for transparent segmentation reporting and data sharing to ensure reproducibility and cross-study comparability in MRS research.

Indexed as

BrainImage Processing, Computer-AssistedMagnetic Resonance ImagingAdultAlgorithmsCreatineFemaleHumansMagnetic Resonance SpectroscopyMaleReproducibility of ResultsCreatineANTsFSLmagnetic resonance spectroscopymetabolite quantificationSPMtissue segmentation

Identifiers

PMID41964041
PMCPMC13269192

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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.