Reliability of spinal cord measures based on synthetic T₁-weighted MRI derived from multiparametric mapping (MPM)

Short MRI acquisition time, high signal-to-noise ratio, and high reliability are crucial for image quality when scanning healthy volunteers and patients. Cross-sectional cervical cord area (CSA) has been suggested as a marker of neurodegeneration and potential outcome measure in clinical trials and is conventionally measured on T₁-weigthed 3D Magnetization Prepared Rapid Acquisition Gradient-Echo (MPRAGE) images. This study aims to reduce the acquisition time for the comprehensive assessment of the spinal cord, which is typically based on MPRAGE for morphometry and multi-parameter mapping (MPM) for microstructure. The MPRAGE is replaced by a synthetic T₁-w MRI (synT₁-w) estimated from the MPM, in order to measure CSA. SynT₁-w images were reconstructed using the MPRAGE signal equation based on quantitative maps of proton density (PD), longitudinal (R₁) and effective transverse (R₂*) relaxation rates. The reliability of CSA measurements from synT₁-w images was determined within a multi-center test-retest study format and validated against acquired MPRAGE scans by assessing the agreement between both methods. The response to pathological changes was tested by longitudinally measuring spinal cord atrophy following spinal cord injury (SCI) for synT₁-w and MPRAGE using linear mixed effect models. CSA measurements based on the synT₁-w MRI showed high intra-site (Coefficient of variation [CoV]: 1.43% to 2.71%) and inter-site repeatability (CoV: 2.90% to 5.76%), and only a minor deviation of -1.65 mm² compared to MPRAGE. Crucially, by assessing atrophy rates and by comparing SCI patients with healthy controls longitudinally, differences between synT₁-w and MPRAGE were negligible. These results demonstrate that reliable estimates of CSA can be obtained from synT₁-w images, thereby reducing scan time significantly.