Age, Gender and Normalization Covariates for Spinal Cord Gray Matter and Total Cross-Sectional Areas at Cervical and Thoracic Levels: A 2D Phase Sensitive Inversion Recovery Imaging Study

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.

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis

“…The accuracy has been further validated in the present study in 5 randomly selected patients with ALS and showed satisfactory results (Dice coefficient in the GM ϭ 0.708) in comparison with healthy controls from a previous study 8 (Dice coefficient in the GM ϭ 0.711). Whereas previous studies have reported that the CSA of the SC is associated with morphologic features such as brain volume 29 and total intracranial volume, 30 the correlations were mild, and there is no clear consensus as to what is the best normalization method to use 31 ; several published studies have not performed CSA normalization, 3,26,[31][32][33] and neither did we in the present study. Future work could further investigate methods for normalization, and specifically for the GMCSA.…”

“…As investigated in a previous study, 30 age and sex could affect both SC and GMCSA. In the present study, the controls and patients were age-matched but not sex-matched (number of women, 6 with ALS versus 11 controls).…”

“…However, the larger proportion of women in the control group would in fact decrease the sensitivity to detect a CSA difference between controls and patients, given that both SC and GM are smaller in women compared with men. 30 Although it would have been relevant to measure CSA in the lateral and anterior funiculi, the current MR imaging protocol, which is based on T2*-weighted contrast, made it impossible to distinguish the anterior and lateral fasciculus from the rest of the WM tissue. Therefore, it was not feasible to measure specific CSAs of these tracts from our data.…”

Gray vs. White Matter Segmentation of the Conus Medullaris: Reliability and Variability in Healthy Volunteers

“…In multiple sclerosis (MS), these measures in the cervical and thoracic SC have been shown to correlate independently with measures of physical disability . Moreover, it has recently been demonstrated in healthy controls that the sensitivity and specificity of these morphometric assessments could improve further by accounting for the effects of different covariates such as age, gender, brain volumes, and skull‐ and vertebra‐derived metrics …”

Spinal Cord as an Adjunct to Brain Magnetic Resonance Imaging in Defining “No Evidence of Disease Activity” in Multiple Sclerosis

“…10 A growing body of evidence has determined that spinal cord MRI involvement shows a particularly close association with MSrelated disability. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] In addition, spinal cord involvement manifests early in the disease course; such lesions in presymptomatic at-risk individuals predict conversion to overt MS. 25 Adding more relevance to the need to consider spinal cord involvement in MS is the observation that such involvement may progress independently from the brain.…”