Charting Cervical Spinal Cord Morphometry Across the Lifespan

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Abstract
Spinal cord morphometry provides essential biomarkers of neurological health, but clinical interpretations are confounded by inter-subject variability and a lack of normative references across the full human lifespan. We address this gap by generating the first comprehensive lifespan charts for cervical spinal cord morphometry. We leveraged 30 population-based brain MRI datasets, aggregating 78,269 scans from 41,042 individuals (ages 0–100) whose imaging protocols included cervical cord coverage. To overcome contrast variability, we employed a state-of-the-art contrast-agnostic deep learning segmentation method, extracting cross-sectional area (CSA), anteroposterior (AP) and right–left (RL/transverse), and shape indices (compression ratio, eccentricity, and solidity) from C1 to C7. Normative trajectories were modeled using Generalized Additive Models for Location, Scale, and Shape (GAMLSS). The resulting charts reveal distinct non-linear lifespan changes: rapid growth through childhood and adolescence, peak maturation occurring in early-to-mid adulthood (e.g., mid-30s for CSA), followed by gradual decreases. Significant regional variations along the cervical cord and consistent sex differences (males > females for size metrics) were quantified. Spinal cord trajectories showed strong temporal coupling with brain white matter and brainstem volumes, suggesting integrated CNS development and aging. These lifespan charts provide a robust normative framework, enabling age- and sex-specific centile scoring of individual spinal cord morphometry. This resource offers a critical tool for differentiating typical variation from pathological changes, enhancing the clinical utility of spinal cord MRI in studies of development and neurodegeneration.
Funding Information
  • National Institutes of Health (R21MH101321)
  • National Institutes of Health (R01MH102272)
  • National Institutes of Health (R01-HD114489)
  • National Institutes of Health (U24 AG074855)
  • National Institutes of Health (U01 AG068057)
  • National Institutes of Health (R01 AG059716)
  • European Union’s Horizon Europe research and innovation programme (101107932)

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