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

Authors

Olga Dmitrichenko, Giuseppina Baldizzi, Tatjana Schmidt, Aurélie Bussy, Olivier Colliot, Antoine Lutti, Ferath Kherif, Bogdan Draganski

Published in

NeuroImage. Clinical. Volume 51. Pages 104039. Jul 21, 2026. Epub Jul 21, 2026.

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.

PMID:
42492140
Bibliographic data and abstract were imported from PubMed on 24 Jul 2026.

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