NORMATIVE NEUROMELANIN-SENSITIVE MRI TRAJECTORIES ACROSS THE LIFESPAN: METHODOLOGICAL INFLUENCES ON BRAINSTEM SIGNAL QUANTIFICATION

Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) enables in vivo characterization of brainstem nuclei implicated in aging and neurodegeneration. Interpretation of NM-MRI signals, however, is complicated by age-related biological variation and by methodological heterogeneity in segmentation and quantification. Establishing robust normative trajectories in healthy populations is therefore a critical prerequisite for reliable clinical application.
NM-MRI data from a large cohort of healthy individuals spanning childhood to late adulthood were analyzed alongside high-resolution anatomical imaging. Multiple segmentation strategies, including atlas-based and probabilistic approaches, were applied to delineate brainstem regions of interest. Neuromelanin-sensitive signal metrics were extracted and modeled as a function of age using flexible non-linear regression frameworks, allowing data-driven characterization of lifespan trajectories. Segmentation approaches were systematically compared with respect to signal stability, reliability, and sensitivity to age-related effects.
Across segmentation methods, neuromelanin-sensitive signal exhibited pronounced age dependence, with non-linear trajectories consistent with developmental and aging-related modulation. While absolute signal estimates varied between segmentation approaches, age-related patterns were consistently observed. Methodological choices substantially influenced trajectory shape, uncertainty, and downstream interpretability.
These findings highlight the importance of normative lifespan modeling and careful methodological selection in neuromelanin-sensitive MRI research. By delineating age-dependent signal trajectories and quantifying the impact of segmentation strategies, this work provides a methodological foundation for future studies aiming to detect pathological deviations in neurodegenerative disease.