Tissue damage and impaired processing speed are related to brain parenchyma free water fraction in multiple sclerosis

In 99 relapsing-remitting multiple sclerosis (MS) patients and 25 healthy controls we quantified cerebral free water fraction (FWF) and investigated its relationship with lesion burden and information processing speed, measured with Symbol Digit Modalities Test (SDMT). FWF was obtained from the mcDESPOT method, fitting a three-compartment relaxation model to spoiled-gradient-echo and balanced-SSFP signals with varying flip angles. MS patients showed higher FWF than controls, in the lesioned tissue and in normal appearing white matter (NAWM). In NAWM and perilesional tissue, FWF correlated with lesion load. FWF spatial heterogeneity increased with worsening SDMT performance in regions involved in MS-related cognitive impairment.