Manual and automated tissue segmentation confirm the impact of thalamus atrophy on cognition in multiple sclerosis: A multicenter study

Abstract

Atrofia; IRM; Esclerosis múltiple

Atròfia; IRM; Esclerosi múltiple

Atrophy; MRI; Multiple Sclerosis

Background and rationale Thalamus atrophy has been linked to cognitive decline in multiple sclerosis (MS) using various segmentation methods. We investigated the consistency of the association between thalamus volume and cognition in MS for two common automated segmentation approaches, as well as fully manual outlining. Methods Standardized neuropsychological assessment and 3-Tesla 3D-T1-weighted brain MRI were collected (multi-center) from 57 MS patients and 17 healthy controls. Thalamus segmentations were generated manually and using five automated methods. Agreement between the algorithms and manual outlines was assessed with Bland-Altman plots; linear regression assessed the presence of proportional bias. The effect of segmentation method on the separation of cognitively impaired (CI) and preserved (CP) patients was investigated through Generalized Estimating Equations; associations with cognitive measures were investigated using linear mixed models, for each method and vendor. Results In smaller thalami, automated methods systematically overestimated volumes compared to manual segmentations [ρ=(-0.42)-(-0.76); p-values < 0.001). All methods significantly distinguished CI from CP MS patients, except manual outlines of the left thalamus (p = 0.23). Poorer global neuropsychological test performance was significantly associated with smaller thalamus volumes bilaterally using all methods. Vendor significantly affected the findings. Conclusion Automated and manual thalamus segmentation consistently demonstrated an association between thalamus atrophy and cognitive impairment in MS. However, a proportional bias in smaller thalami and choice of MRI acquisition system might impact the effect size of these findings.

The study was funded by the Nauta fonds through a travel grant. The MS Center Amsteram is supported by the Dutch MS Research Foundation through a program grant (current grant 18-358f). D.B. is supported by project PI18/00823 from the “Fondo de Investigación Sanitaria Carlos III”. F.B. and O.C. are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The acquisition of data in London was funded by supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A sincere thank you to Tom Verhoeven for his editing of the figures.