Normalization of Spinal Cord Total Cross-Sectional and Gray Matter Areas as Quantified With Radially Sampled Averaged Magnetization Inversion Recovery Acquisitions

Abstract

Background: MR imaging of the spinal cord (SC) gray matter (GM) at the cervical and lumbar enlargements' level may be particularly informative in lower motor neuron disorders, e. g., spinal muscular atrophy, but also in other neurodegenerative or autoimmune diseases affecting the SC. Radially sampled averaged magnetization inversion recovery acquisition (rAMIRA) is a novel approach to perform SC imaging in clinical settings with favorable contrast and is well-suited for SC GM quantitation. However, before applying rAMIRA in clinical studies, it is important to understand (i) the sources of inter-subject variability of total SC cross-sectional areas (TCA) and GM area (GMA) measurements in healthy subjects and (ii) their relation to age and sex to facilitate the detection of pathology-associated changes. In this study, we aimed to develop normalization strategies for rAMIRA-derived SC metrics using skull and spine-based metrics to reduce anatomical variability. Methods: Sixty-one healthy subjects (age range 11-93 years, 37.7% women) were investigated with axial two-dimensional rAMIRA imaging at 3T MRI. Cervical and thoracic levels including the level of the cervical (C4/C5) and lumbar enlargements (T_max) were examined. SC T2-weighted sagittal images and high-resolution 3D whole-brain T1-weighted images were acquired. TCA and GMAs were quantified. Anatomical variables with associations of |r| > 0.30 in univariate association with SC areas, and age and sex were used to construct normalization models using backward selection with TCA_C4/C5 as outcome. The effect of the normalization was assessed by % relative standard deviation (RSD) reductions. Results: Mean inter-individual variability and the SD of the SC area metrics were considerable: TCA_C4/5: 8.1%/9.0; TCA_Tmax: 8.9%/6.5; GMA_C4/C5: 8.6%/2.2; GMA_Tmax: 12.2%/3.8. Normalization based on sex, brain WM volume, and spinal canal area resulted in RSD reductions of 23.7% for TCAs and 12.0% for GM areas at C4/C5. Normalizations based on the area of spinal canal alone resulted in RSD reductions of 10.2% for TCAs and 9.6% for GM areas at C4/C5, respectively. Discussion: Anatomic inter-individual variability of SC areas is substantial. This study identified effective normalization models for inter-subject variability reduction in TCA and SC GMA in healthy subjects based on rAMIRA imaging.

Keywords: MRI; inter-subject variability; minors; normalization; spinal cord gray matter imaging; spinal muscular atrophy.

Figure 1

rAMIRA images of the spinal cord in an 11-year-old boy. From left to right: axial rAMIRA images at intervertebral disc level C4/C5 (top row) and T_max (bottom row) acquired at five inversion times (TI), mean image (combination of the images at five TIs); and mean images with the region of interests (ROIs) spinal cord total cross-sectional area (TCA, green) and gray matter area (GMA, yellow) which were segmented using the software JIM.

Figure 2

Definition of the skeletal metrics. (A) Sagittal T1 weighted MPRAGE: McRae line (distance between Basion–Opisthion). (B) Axial MPRAGE: anterior posterior and lateral diameters, as well as area of the foramen magnum. (C) Axial rAMIRA: Maximum axial anterior posterior and lateral spinal canal diameters, spinal canal area, maximum lateral vertebral body width. (D) Sagittal T2 weighted turbo spin echo: middle vertebra height C4 and T12.

Figure 3

Normalization effects of Model 1 and Model 2 on total cross-sectional cord areas and gray matter areas at all cord levels. The % relative standard deviation (RSD, standard deviation divided by the mean area) and relative % RSD reduction obtained by normalization based on Model 1 (sex, brain white matter volume and spinal canal area at the level C4/C5) as well as by Model 2 (spinal canal area at the level C4/C5) for (A) total cross-sectional cord areas and (B) spinal cord gray matter areas (whole study population, n = 61).