Assessing neuronal metabolism in vivo by modeling imaging measures

Mitochondrial dysfunction contributes to the pathogenesis of many neurological diseases, including multiple sclerosis (MS), but is not directly measurable in vivo. We modeled N-acetyl-aspartate (NAA), which reflects axonal structural integrity and mitochondrial metabolism, with imaging measures of axonal structural integrity (axial diffusivity and cord cross-sectional area) to extract its mitochondrial metabolic contribution. Lower residual variance in NAA, reflecting reduced mitochondrial metabolism, was associated with greater clinical disability in MS, independent of structural damage.