Water is a common internal reference for metabolite quantification by 1H-MRS. We investigate potential influences on water-referenced metabolite quantification by differences in frontal cortex water T2 in individuals with relapsing-remitting, progressive, and no multiple sclerosis. Water T2 differed in monoexponential models, exhibiting highest values in progressive multiple sclerosis only when analyses were not age-controlled. Groupwise T2 did not differ in biexponential models constrained by tissue and CSF partial volumes, suggesting that monoexponential T2 differences reflected disparate proportions of water in tissue and CSF rather than differential behavior within them. Our results suggest stability of water T2 within frontal cortex tissue and CSF with multiple sclerosis and emphasize the superiority of metabolite quantification with group-specific T2 values when voxel composition may differ.
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