Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject’s sex and age. However, corrections for body size (i.e., height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1 ± 6.6 years old, 125 females). We show that body height correlates with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44 ≤ r ≤ 0.62). Intracranial volume (ICV) correlates with body height (r = 0.46) and the brain volumes and CSA-WM (0.37 ≤ r ≤ 0.77). In comparison, age correlates with cortical GM volume, precentral GM volume, and cortical thickness (-0.21 ≥ r ≥ -0.27). Body weight correlates with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20 ≥ r ≥ -0.23). Body weight further correlates with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r = -0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlates with brain volumes (0.39 ≤ r ≤ 0.64), and with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22 ≥ r ≥ -0.25). Linear mixture of age, sex, or sex and age, explained 2 ± 2%, 24 ± 10%, or 26 ± 10%, of data variance in brain volumetry and SC CSA. The amount of explained variance increased to 33 ± 11%, 41 ± 17%, or 46 ± 17%, when body height, ICV, or body height and ICV were added into the mixture model. In females, the explained variances halved suggesting another unidentified biological factor(s) determining females’ central nervous system (CNS) morphology. In conclusion, body size and ICV are significant biological variables. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure; and body size and ICV should be considered as covariates in statistical analyses. Normalization of different brain regions with ICV diminishes their correlations with body size, but simultaneously amplifies ICV-related variance (r = 0.72 ± 0.07) and suppresses volume variance of the different brain regions (r = 0.12 ± 0.19) in the normalized measurements.

Measures of spinal cord morphometry computed from magnetic resonance images serve as relevant prognostic biomarkers for a range of spinal cord pathologies, including traumatic and non-traumatic spinal cord injury and neurodegenerative diseases. However, interpreting these imaging biomarkers is difficult due to considerable intra- and inter-subject variability. Yet, there is no clear consensus on a normalization method that would help reduce this variability and more insights into the distribution of these morphometrics are needed. In this study, we computed a database of normative values for six commonly used measures of spinal cord morphometry: cross-sectional area, anteroposterior diameter, transverse diameter, compression ratio, eccentricity, and solidity. Normative values were computed from a large open-access dataset of healthy adult volunteers (N = 203) and were brought to the common space of the PAM50 spinal cord template using a newly proposed normalization method based on linear interpolation. Compared to traditional image-based registration, the proposed normalization approach does not involve image transformations and, therefore, does not introduce distortions of spinal cord anatomy. This is a crucial consideration in preserving the integrity of the spinal cord anatomy in conditions such as spinal cord injury. This new morphometric database allows researchers to normalize based on sex and age, thereby minimizing inter-subject variability associated with demographic and biological factors. The proposed methodology is open-source and accessible through the Spinal Cord Toolbox (SCT) v6.0 and higher.