A Radiomic Approach to Clinical MRI Refines the Thalamus-Cognition Link in Multiple Sclerosis

Abstract

Background and ObjectivesRadiomics extracts imaging features that may not be detectable through conventional volumetric analyses. Given their role in multiple sclerosis (MS), we applied radiomics to thalamic nuclei and examined their associations with cognitive performance. MethodsA total of 601 individuals were included (342 people with MS-PwMS from two cohorts, and 259 healthy controls-HC). Radiomic features (RF) and volumes were extracted from the whole thalamus, five thalamic nuclei, and the putamen segmented on 3D T1-weighted images. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT) in PwMS, and the Digit Symbol Substitution Test (DSST) in HC. In the first MS cohort, multivariate linear regression in a discovery set (N=103) identified thalamus-derived RF associated with SDMT, which were retested in a replication set (N=63). Their associations with PASAT in a second MS cohort (N=176) and DSST in HC were also evaluated. We then tested whether the same RF, when extracted from the putamen, were associated with SDMT. LASSO models assessed the combined predictive value of RF and volumes. Figure 2 presents an overview of the involvement of different cohorts in the study, outlining the specific study objectives and the statistical analysis approaches employed. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/657698v1_fig2.gif" ALT="Figure 2"> View larger version (40K): org.highwire.dtl.DTLVardef@6f1dd8org.highwire.dtl.DTLVardef@11069c6org.highwire.dtl.DTLVardef@905512org.highwire.dtl.DTLVardef@1c12171_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO Overview of the involvement of different cohorts in the study, specific study objectives and the statistical analysis approaches employed. Abbreviations: SDMT: Symbol Digit Modalities Test, PASAT: Paced Auditory Serial Addition Test, DSST: Digit Symbol Substitution Test, LASSO: Least Absolute Shrinkage and Selection Operator. C_FIG ResultsTwenty-eight RF-ROI pairs were associated with SDMT in the replication set (FDR<0.05). Of these, 24 were also associated with PASAT (FDR[≤]0.03), and 2 with DSST. Only ventral nuclei volume showed replicated associations among volumetrics. Only 4 putamen-derived pairs were associated with SDMT (FDR=0.04). LASSO results confirmed RF outperformed volumes. DiscussionRF extracted from the thalamus are strongly associated with cognitive performance in PwMS, outperforming volumetric measures and supporting their potential as sensitive imaging biomarkers.