The quest for the best: manual, atlas- and spatial prior-based delineation of locus coeruleus.

Overview

1. Imaging Neuroscience of Ageing – inAGE laboratory, Neurology Department - Inselspital, University Hospital Bern, University Bern, Bern, Switzerland
2. Graduate School for Health Sciences, University of Bern, Switzerland
3. Department of Clinical Neurosciences, University of Cambridge, Cambridge, Biomedical Campus, UK
4. Sorbonne Université, Institut du Cerveau – Paris Brain Institute - ICM, CNRS, Inria, Inserm, AP-HP, Hôpital de la Pitié-Salpêtrière, Paris, France
5. Laboratory for Neuroimaging Research, Department of Clinical Neuroscience, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
6. University Institute for Diagnostic and Interventional Neuroradiology - Inselspital, University Hospital Bern, University Bern, Bern, Switzerland

Abstract

Despite advances in neuromelanin-sensitive brain imaging and a plethora of software solutions, the reliable non-invasive delineation of the locus coeruleus (LC) in the human brainstem remains challenging. We sought to evaluate the spatial accuracy and consistency of atlas- and probabilistic spatial prior-based LC delineation. We acquired neuromelanin-sensitive 3 T MRI data in healthy volunteers (n = 24; mean age 40.0 ± 16.8 years; 42% female). Manual labelling by 9 raters performed twice provided the basis for individual- and group-level comparisons, showing moderate inter-rater agreement (mean Dice = 0.7). For the atlas-based labelling, we tested seven open-access LC atlases, a consensus reference representing the atlases' overlap and the averaged manual labelling. Open-access atlases demonstrated low spatial concordance (Dice = 0.2–0.4), while the averaged manual labelling atlas had higher spatial overlap (Dice = 0.6). Probabilistic delineation using spatial priors showed the strongest voxel-wise similarity with manual labelling (r = 0.3) when the averaged manual labelling atlas was used as prior. Principal component analysis confirmed the greater spatial compactness for atlas-based labelling. Atlas-based labelling using the averaged manual labelling atlas in an extended 3 T cohort (n = 2393, mean age 58.44 ± 13.75 years) identified that tissue myelin and iron declined continuously from early adulthood, while free tissue water increased – a neurobiological trend robust to atlas choice. LC volume showed an inverted-U trajectory. Our results highlight the potential of atlas-based labelling for LC identification and demonstrate its sensitivity to physiologically grounded aging processes, suggesting that harmonised validation strategies and context-sensitive approaches can improve reliability.

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

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Data will be made available on request.

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

Data Availability Statement

The data from the CoLaus|PsyCoLaus cohort used in this study cannot be fully shared due to the inclusion of potentially sensitive patient information. According to the competent authority, the Research Ethic Committee of the Canton of Vaud, Switzerland, sharing or transferring this data would violate Swiss legislation designed to protect participants' personal rights. However, non-identifiable, individual-level data can be made available to researchers who meet the criteria for accessing confidential data, for detailed instructions please see https://www.colaus-psycolaus.ch/professionals/how-to-collaborate/) by CoLaus|PsyCoLaus Datacenter (CHUV, Lausanne, Switzerland). Code to all analyses and figures will be uploaded to https://github.com/dmiolga/LC_delineation.git once the paper has been accepted.

Data will be made available on request.

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

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 8 authors, 6 keywords, 12 MeSH terms, 4 funders, 85 references.

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This paper

Dmitrichenko, O., Baldizzi, G., Schmidt, T., Bussy, A., Colliot, O., Lutti, A., Kherif, F., & Draganski, B. (2026). The quest for the best: manual, atlas- and spatial prior-based delineation of locus coeruleus. NeuroImage. Clinical, 51, 104039. https://doi.org/10.1016/j.nicl.2026.104039

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