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Peer-reviewedCC BYImaging neuroscience (Cambridge, Mass.)

Assessing the reliability of hippocampal single-voxel proton magnetic resonance spectroscopy through intra-class effect decomposition.

  • Martin Nilsson1
  • Jonathan Berrebi2
  • Sahar Nikkhou-Aski3,4
  • Bárbara Avelar-Pereira1,5
  • Per Thorsell1
  • Vlad Legendi6
  • Marc Guitart-Masip7
  • Goran Papenberg1
7 affiliations
  1. 1Aging Research Center, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Stockholm University, Sweden.
  2. 2Stockholm University Brain Imaging Centre, Stockholm University, Stockholm, Sweden.
  3. 3Department of Nuclear medicine and Medical Physics, Karolinska University Hospital Solna, Stockholm, Sweden.
  4. 4Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
  5. 5Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, United States.
  6. 6Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde, Sweden.
  7. 7Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
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Abstract

The hippocampus is crucial for learning, memory, and stress regulation, but is vulnerable to influences that compromise its structural and metabolic integrity. Proton magnetic resonance spectroscopy (MRS) enables in vivo quantification of hippocampal neurochemistry, yet the absolute and relative reliability of these measures has rarely been systematically evaluated. We assessed hippocampal metabolite estimates acquired with single-voxel MRS using a semi-adiabatic localization by adiabatic selective refocusing (semi-LASER) sequence at 3 T. Nineteen healthy adults (8 male; mean age = 40.9 ± 16.9 years) underwent four measurements across 2 consecutive days, with one session including an extended acquisition. Absolute reliability was quantified using within-subject coefficients of variation (CVs), and relative reliability was estimated with the Intra-Class Effect Decomposition (ICED) framework, which partitions variance into true-score, day-specific, session-specific, and residual components. Despite good spectral quality and high absolute reliability for several metabolites, relative reliability ranged from poor to good. Good relative reliability was observed only for water-referenced myo-inositol, total choline, and total creatine; no creatine-referenced metabolite reached this threshold. Increasing the number of transients increased signal-to-noise ratio but did not improve relative reliability; only creatine-referenced total N-acetylaspartate showed significant session-specific variance. Thus, high absolute reliability did not necessarily imply high relative reliability. Hippocampal MRS at 3 T may, therefore, be suitable for group-level or mean-level metabolite estimates, but appears less suitable for correlational, biomarker, or other individual-difference applications that require stable between-person differences. Methodological refinement, including improved voxel placement, motion correction, shimming, and quantification pipelines, may improve the relative reliability of hippocampal MRS.

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Cite

BibTeXRIS
BibTeX
@article{nilsson2026assessing,
  title = {{Assessing the reliability of hippocampal single-voxel proton magnetic resonance spectroscopy through intra-class effect decomposition.}},
  author = {Martin Nilsson and Jonathan Berrebi and Sahar Nikkhou-Aski and Bárbara Avelar-Pereira and Per Thorsell and Vlad Legendi and Marc Guitart-Masip and Goran Papenberg},
  journal = {Imaging neuroscience (Cambridge, Mass.)},
  year = {2026},
  month = oct,
  doi = {10.1162/imag.a.1401},
  url = {https://europepmc.org/article/MED/42903583},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Assessing the reliability of hippocampal single-voxel proton magnetic resonance spectroscopy through intra-class effect decomposition.
AU  - Martin Nilsson
AU  - Jonathan Berrebi
AU  - Sahar Nikkhou-Aski
AU  - Bárbara Avelar-Pereira
AU  - Per Thorsell
AU  - Vlad Legendi
AU  - Marc Guitart-Masip
AU  - Goran Papenberg
PY  - 2026
DA  - 2026/10/16
JO  - Imaging neuroscience (Cambridge, Mass.)
DO  - 10.1162/imag.a.1401
UR  - https://europepmc.org/article/MED/42903583
AB  - The hippocampus is crucial for learning, memory, and stress regulation, but is vulnerable to influences that compromise its structural and metabolic integrity. Proton magnetic resonance spectroscopy (MRS) enables in vivo quantification of hippocampal neurochemistry, yet the absolute and relative reliability of these measures has rarely been systematically evaluated. We assessed hippocampal metabolite estimates acquired with single-voxel MRS using a semi-adiabatic localization by adiabatic selective refocusing (semi-LASER) sequence at 3 T. Nineteen healthy adults (8 male; mean age = 40.9 ± 16.9 years) underwent four measurements across 2 consecutive days, with one session including an extended acquisition. Absolute reliability was quantified using within-subject coefficients of variation (CVs), and relative reliability was estimated with the Intra-Class Effect Decomposition (ICED) framework, which partitions variance into true-score, day-specific, session-specific, and residual components. Despite good spectral quality and high absolute reliability for several metabolites, relative reliability ranged from poor to good. Good relative reliability was observed only for water-referenced myo-inositol, total choline, and total creatine; no creatine-referenced metabolite reached this threshold. Increasing the number of transients increased signal-to-noise ratio but did not improve relative reliability; only creatine-referenced total N-acetylaspartate showed significant session-specific variance. Thus, high absolute reliability did not necessarily imply high relative reliability. Hippocampal MRS at 3 T may, therefore, be suitable for group-level or mean-level metabolite estimates, but appears less suitable for correlational, biomarker, or other individual-difference applications that require stable between-person differences. Methodological refinement, including improved voxel placement, motion correction, shimming, and quantification pipelines, may improve the relative reliability of hippocampal MRS.
SN  - 2837-6056
ER  -