Samuelle St-Onge

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. From 78,269 T1‐weighted brain MRI sessions, we identified a final cross‐sectional cohort of 24,251 healthy or cognitively normal controls from 33 datasets (ages 0–100 years) with 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 (AP/RL 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.

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.

Parkinson’s disease (PD) is primarily defined by brain pathology, including dopamine neuron degeneration and α-synuclein aggregation. Emerging evidence suggests that the spinal cord is also affected, with ex-vivo studies reporting abnormal α-synuclein protein aggregation within the spinal cord of PD patients. While advanced imaging techniques, such as diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), T2*-weighted (T2*w) imaging, and the magnetization transfer ratio (MTR) have demonstrated potential for detecting PD-related changes in the brain, their application to uncover spinal cord alterations remains unexplored. This study is the first to investigate MRI-derived microstructural metrics in the spinal cord of PD patients, comparing them to healthy controls. Although this study found limited microstructural or structural differences in the spinal cord between PD patients and healthy controls, these findings are consistent with recent results from PD mouse models and complement an earlier functional MRI study using the same cohort, where significant findings were observed. Our lack of significant structural findings may suggest that functional spinal cord changes are more sensitive markers of Parkinson’s disease progression—particularly in relation to clinical measures such as the Unified Parkinson’s Disease Rating Scale (UPDRS). These results highlight the need for further research to better understand how PD-related alterations in the spinal cord compare to normal aging processes and relate to functional changes.

The spinal cord connects the brain to peripheral systems. Yet its integration with cerebral networks remains a key neuroscience question. Capturing structural and functional central nervous system (CNS) changes throughout the lifespan is essential for characterizing healthy and pathological aging. Leveraging a unique multimodal dataset combining spinal and cerebrospinal imaging, we jointly mapped the spinal cord structural and functional architecture across adulthood. Our results revealed age-related changes across these modalities and identified organizational principles shared with the brain. These changes were most pronounced in the somatosensory pathway, with microstructural decline coupled to shifts in functional connectivity and local spontaneous activity as aging progresses. Extending analyses to the brain uncovered convergent CNS-wide aging mechanisms, including gray matter loss, functional dedifferentiation, and increased spontaneous activity, highlighting shared neural aging trajectories. Together, our findings provide a systems-level view of alterations with age and lay the groundwork for early biomarkers of sensorimotor decline.

Parkinson's disease (PD) is primarily defined by brain pathology, including dopamine neuron degeneration and α-synuclein aggregation. Emerging evidence suggests that the spinal cord is also affected, with ex-vivo studies reporting abnormal α-synuclein protein aggregation within the spinal cord of PD patients. While advanced imaging techniques, such as diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), T2-weighted (T2w) imaging, and the magnetization transfer ratio (MTR) have demonstrated potential for detecting PD-related changes in the brain, their application to uncover spinal cord alterations remains unexplored. This study is the first to investigate MRI-derived microstructural metrics in the spinal cord of PD patients, comparing them to healthy controls. Although this study found limited microstructural or structural differences in the spinal cord between PD patients and healthy controls, these findings are consistent with recent results from PD mouse models and complement an earlier functional MRI study using the same cohort, where significant findings were observed. Our lack of significant structural findings may suggest that functional spinal cord changes are more sensitive markers of Parkinson's disease progression-particularly in relation to clinical measures such as the Unified Parkinson's Disease Rating Scale (UPDRS). These results highlight the need for further research to better understand how PD-related alterations in the spinal cord compare to normal aging processes and relate to functional changes.