Intersubject Variability and Normalization Strategies for Spinal Cord Total Cross‐Sectional and Gray Matter Areas

Abstract

Background and Purpose-The quantification of spinal cord (SC) atrophy by MRI has assumed an important role in assessment of neuroinflammatory/neurodegenerative diseases and traumatic SC injury. Recent technical advances make possible the quantification of gray matter (GM) and white matter tissues in clinical settings. However, the goal of a reliable diagnostic, prognostic or predictive marker is still elusive, in part due to large inter-subject variability of SC areas. Here, we investigated the sources of this variability and explored effective strategies to reduce it.Methods-129 healthy subjects (mean age: 41.0±15.9) underwent MRI on a Siemens 3T Skyra scanner. 2D PSIR at the C2-C3 vertebral level and a sagittal 1mm 3 3D T1-weighted brain acquisition extended to the upper cervical cord were acquired. Total cross-sectional area and GM area were measured at C2-C3, as well as measures of the vertebra, spinal canal and the skull. Correlations between the different metrics were explored using Pearson product-moment coefficients. The most promising metrics were used to normalize cord areas using multiple regression analyses.Results-The most effective normalization metrics were the V-scale (from SienaX) and the product of the C2-C3 spinal canal diameters. Normalization methods based on these metrics reduced the inter-subject variability of cord areas of up to 17.74%. The measured cord areas had a statistically significant sex difference, while the effect of age was moderate.Conclusions-The present work explored in a large cohort of healthy subjects the source of inter-subject variability of SC areas and proposes effective normalization methods for its reduction.

MRI Measurement of Upper Cervical Spinal Cord Cross‐Sectional Area in Children

“…To compute CSA and canal measurements analogously to previous work, the sagittal MPRAGE was resampled on the axial plane creating a packet of five contiguous slices 1‐mm thick centered at the C2‐C3 intervertebral disc 9,10 . CSA was measured semi‐automatically on these five slices and the average value computed, using the Jim “cord finder” toolkit with pre‐established settings (nominal cord diameter, 8 mm; number of shape coefficients, 24; order of longitudinal variation, 12), after manual marker placement at the cord center of each of the five slices.…”

“…To be used for the intersubject normalizing methods, a trained operator (CA) manually measured the maximum anterior‐posterior diameter and lateral diameter of the vertebral canal on the central slice of the five‐slice packet. The product of the two diameters was computed as previously described to get the “axial_canal_product” metric 10 . V‐scale was obtained using SienaX (part of FSL) 14 …”

“…The three best normalization strategies developed and tested in our previous work on adults were applied to the CSA values extracted for the 78 children 10 …”

“…The effect of the normalization by a particular selected model was evaluated by comparing the coefficient of variation (%COV, ratio of the group standard deviation and the respective means expressed as percentage) between the measured data and the values generated by the respective correction formulas 10,15,16 …”

“…Thanks to the reliability of our 2‐dimensional PSIR‐based acquisition/measurement method, we could recently assess SC cervical CSA and GM areas at the C2‐C3 intervertebral disc level in 129 adult healthy subjects (mean age: 41.0 ± 15.9; range: 19‐79) 10 . We explored the influence of age and sex on SC areas, finding a stronger influence of sex than age‐related decline in cord areas.…”