Minimum detectable spinal cord atrophy with automatic segmentation: Investigations using an open-access dataset of healthy participants

Spinal cord atrophy is a well-known biomarker in multiple sclerosis (MS) and other diseases. It is measured by segmenting the spinal cord on an MRI image and computing the average cross-sectional area (CSA) over a few slices. Introduced about 25 years ago, this procedure is highly sensitive to the quality of the segmentation and is prone to rater-bias. Recently, fully-automated spinal cord segmentation methods, which remove the rater-bias and enable the automated analysis of large populations, have been introduced. A lingering question related to these automated methods is: How reliable are they at detecting atrophy? In this study, we evaluated the precision and accuracy of automated atrophy measurements by simulating scan-rescan experiments. Spinal cord MRI data from the open-access spine-generic project were used. The dataset aggregates 42 sites worldwide and consists of 260 healthy subjects and includes T1w and T2w contrasts. To simulate atrophy, each volume was globally rescaled at various scaling factors. Moreover, to simulate patient repositioning, random rigid transformations were applied. Using the DeepSeg algorithm from the Spinal Cord Toolbox, the spinal cord was segmented and vertebral levels were identified. Then, the average CSA between C3-C5 vertebral levels was computed for each Monte Carlo sample, allowing us to derive measures of atrophy, intra/inter-subject variability, and sample-size calculations. The minimum sample size required to detect an atrophy of 2% between unpaired study arms, commonly seen in MS studies, was 467 +/− 13.9 using T1w and 467 +/− 3.2 using T2w images. The minimum sample size to detect a longitudinal atrophy (between paired study arms) of 0.8% was 60 +/− 25.1 using T1w and 10 +/− 1.2 using T2w images. At the intra-subject level, the estimated CSA, observed in this study, showed good precision compared to other studies with COVs (across Monte Carlo transformations) of 0.8% for T1w and 0.6% for T2w images. While these sample sizes seem small, we would like to stress that these results correspond to a “best case” scenario, in that the dataset used here was of particularly good quality and the model for simulating atrophy does not encompass all the variability met in real-life datasets. The simulated atrophy and scan-rescan variability may over-simplify the biological reality. The proposed framework is open-source and available at https://csa-atrophy.readthedocs.io/.