Upper cervical spinal cord morphometric charts: from population references to individualized clinical assessment

The upper cervical spinal cord is essential for motor, sensory and autonomic function, yet its normative morphometric trajectories and disease-related deviations remain unclear. Using three-dimensional T1-weighted images from 10,159 healthy individuals aged 8-85 years, we established normative references for averaged and level-specific upper cervical spinal cord morphometry, revealing measure-specific trajectories with peak ages of 29.7-44.1 years. These references were applied to 2,394 patients with seven neurological disorders: mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, cerebral small vessel disease, multiple sclerosis, neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease to derive individualized deviation scores. These deviation scores captured disease-specific abnormalities, enabled disease classification, and were associated with cognition, physical disability and disease progression. Finally, a personalized upper cervical spinal cord report was developed to support individualized imaging interpretation. Together, these findings provide a normative framework for quantifying upper cervical spinal cord morphometry and advancing personalized assessment across neurological disorders.