Multiple sclerosis diagnosis and phenotype identification by multivariate classification of in vivo frontal cortex metabolite profiles

Abstract Multiple sclerosis (MS) is a heterogeneous autoimmune disease for which diagnosis continues to rely on subjective clinical judgment over a battery of tests. Proton magnetic resonance spectroscopy ( 1 H MRS) enables the noninvasive in vivo detection of multiple small-molecule metabolites and is therefore in principle a promising means of gathering information sufficient for multiple sclerosis diagnosis and subtype classification. Here we show that supervised classification using 1 H-MRS-visible normal-appearing frontal cortex small-molecule metabolites alone can indeed differentiate individuals with progressive MS from control (held-out validation sensitivity 79% and specificity 68%), as well as between relapsing and progressive MS phenotypes (held-out validation sensitivity 84% and specificity 74%). Post hoc assessment demonstrated the disproportionate contributions of glutamate and glutamine to identifying MS status and phenotype, respectively. Our finding establishes 1 H MRS as a viable means of characterizing progressive multiple sclerosis disease status and paves the way for continued refinement of this method as an auxiliary or mainstay of multiple sclerosis diagnostics.