Exploring brain glucose metabolism in multiple sclerosis: A deuterium metabolic imaging study

Axonal demyelination is a key feature in multiple sclerosis (MS), that is, increasingly linked to a state of energetic failure, however current non-invasive methods to probe downstream metabolic changes are lacking. This study aimed to investigate Deuterium Metabolic Imaging (DMI) to measure alterations in glucose metabolism in MS compared to healthy controls (HC). In this prospective study DMI was performed on eight patients with relapsing-remitting MS (RRMS) together with eight age- and sex-matched HC. Following oral administration of [6,6'-²H₂] glucose, DMI was acquired on 3 T MRI to quantify the metabolic conversion of glucose (Glc) into glutamate and glutamine (Glx) and lactate. White matter (WM) oxidative metabolism (²H-Glx/²H-Water), showed a negative correlation with the Expanded Disability Status Scale score (EDSS) (Pearson r = -0.71, p = 0.049). Glucose (²H-Glc/²H-Water), remained unchanged across EDSS (Pearson r = -0.13, p = 0.76). Impaired glucose levels and oxidative metabolism in WM correlated negatively with increased number of T2-FLAIR lesions (Pearson r = -0.86 to -0.83, respectively). These in vivo findings provide evidence for a relative failure of oxidative energy production within the WM of RRMS compared to HC offering proof of concept that DMI is a feasible tool for measuring neurodegeneration related metabolic changes.