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Background: Patients with multiple sclerosis (MS) may remain in a relapsing-remitting (RRMS) course despite long-standing disease, while others will develop secondary progression (SPMS). Chronic inflammation and changes in the blood-brain barrier resulting in perturbed glucose metabolism may account for these differences. PET-MRI with kinetic analysis of 2-deoxy-2(18 F)fluoro-d-glucose (18 F-FDG) provides insight into glucose metabolism and has proven useful in several chronic inflammatory diseases. However, to our knowledge, it has never been studied in MS., Objective: To explore potential differences in glucose distribution kinetics among individuals with long-standing SPMS and RRMS using dynamic 18-F-FDG PET-MRI., Methods: Dynamic 18-F-FDG PET-MRI scans were obtained in 11 patients with long-standing MS: 4 with RRMS and 7 with SPMS. Kinetic analysis of PET data was performed using a three-compartment model equation that represents plasma, tissue and 18 F-FDG phosphorylation. Individual rate constants of 18-F-FDG across the compartments were calculated., Results: Patients with SPMS exhibited a trend towards an increased net influx rate of glucose (p = 0.059) and an increased rate constant representing glucose phosphorylation. Together, the data suggest increased uptake of glucose and glycolysis in these patients., Conclusion: Dynamic 18 F-FDG PET-MRI is a feasible technique that may show information in vivo of glucose metabolism in MS. Although preliminary data suggest a potential radiological marker of progression in MS, further studies are required to confirm this hypothesis., Competing Interests: Declarations. Ethical standards: The study was approved by the Institutional Ethics Committee at Hospital Universitari I Politècnic La Fe and all patients gave written informed consent to participate in the study. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. Fondazione Società Italiana di Neurologia.)