Abstract

The source of inter-subject variability and the influence of age and gender on morphometric characteristics of the spinal cord, such as the total cross-sectional area (TCA), the gray matter (GM) and white matter (WM) areas, currently remain under investigation. Understanding the effect of covariates such as age, gender, brain volumes, and skull- and vertebra-derived metrics on cervical and thoracic spinal cord TCA and GM areas in healthy subjects would be fundamental for exploring compartment specific changes in neurological diseases affecting the spinal cord. Using Magnetic Resonance Imaging at 3T we investigated 32 healthy subjects using a 2D phase sensitive inversion recovery sequence and we measured TCA, GM and WM areas at 4 cervical and thoracic levels of the spinal cord. We assessed age and gender relationships of cord measures and explored associations between cord measures and a) brain volumes and b) skull- and vertebra-derived metrics. Age and gender had a significant effect on TCA, WM and GM areas (with women and elderly having smaller values than men and younger people respectively), but not on the GM area/TCA ratio. The total intracranial volume and C3 vertebra dimensions showed the highest correlations with cord measures. When used in multi-regression models, they reduced cord areas group variability by approximately a third. Age and gender influences on cord measures and normalization strategies here presented might be of use in the study of compartment specific changes in various neurological diseases affecting the spinal cord.

Highlights

  • The aim of the present work was to extend the previous studies by exploring the effect of covariates such as age and gender on total cross-sectional area (TCA), WM and gray matter (GM) areas at 4 selected cervical and thoracic levels (C2-C3, C3-C4, T8-T9 and T9-T10) of the spinal cord on healthy controls using an acquisition and measurement procedure based on 2D phase-sensitive inversion recovery (PSIR) imaging that was recently shown to allow sensitive and clinically feasible spinal cord assessment of gray and white matter areas in efficient acquisition times of

  • To verify if possible gender differences could be explained by the physical characteristics of the subjects we explored the effect of age, gender, height and weight on the spinal cord areas at cervical and thoracic levels in a multivariate analysis

  • Reliable and clinically feasible acquisition and measurement procedure based on 2D phase-sensitive inversion recovery imaging, we explored age/gender influences on TCA, and GM and WM cord measures and assessed associations between cord measures and a) brain volumes and b) skull- and vertebra-derived metrics to develop normalization strategies to reduce variability of measures

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Summary

Introduction

Spinal cord (SC) atrophy is a common and clinically relevant aspect of various diseases, the effects of which are either confined to the spinal cord or involve the whole central nervous system, such as adrenomyeloneuropathy [1,2], amyotrophic lateral sclerosis [3] and multiple sclerosis (MS) [4,5].Progressive disability in MS is currently thought to be largely driven by spinal cord involvement that may affect both the gray matter (GM) and white matter (WM) compartments [6,7], impacting clinical presentation and disease course.Magnetic Resonance Imaging (MRI) recently enabled in-vivo morphometric assessments of the WM and GM areas of the spinal cord, by using T2Ã weighted imaging [8,9,10,11] or phase-sensitive inversion recovery (PSIR) imaging [12,13,14]. Prior MRI studies that explored age and gender effects on spinal cord metrics in healthy controls were mostly focused on TCA (or cord volume) measurements at the cervical levels [15,16,17,18,19,20,21,22,23,24]. In these studies there was strong agreement regarding the influence of sex on cervical TCA or volumes, with men having larger values compared to women. The majority of the cited papers reported a moderate decrease of cervical cord areas with age, but this behavior was not consistently observed in all studies

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