Neuro-axonal degeneration occurs progressively from the onset of
multiple sclerosis and is thought to be a significant cause of increasing clinical disability. Several histopathological studies of
multiple sclerosis and
experimental autoimmune encephalomyelitis have shown that the accumulation of
sodium in axons can promote reverse action of the
sodium/calcium exchanger that, in turn, leads to a lethal overload in intra-axonal
calcium. We hypothesized that
sodium magnetic resonance imaging would provide an
indicator of cellular and metabolic integrity and ion homeostasis in patients with
multiple sclerosis. Using a three-dimensional radial gradient-echo sequence with short echo time, we performed
sodium magnetic resonance imaging at 3 T in 17 patients with
relapsing-remitting multiple sclerosis and in 13 normal subjects. The absolute total tissue
sodium concentration was measured in lesions and in several areas of normal-appearing white and grey matter in patients, and corresponding areas of white and grey matter in controls. A mixed model analysis of covariance was performed to compare regional tissue
sodium concentration levels in patients and controls. Spearman correlations were used to determine the association of regional tissue
sodium concentration levels in T(2)- and T(1)-weighted lesions with measures of normalized whole brain and grey and white matter volumes, and with expanded disability status scale scores. In patients, tissue
sodium concentration levels were found to be elevated in acute and chronic lesions compared to areas of normal-appearing white matter (P < 0.0001). The tissue
sodium concentration levels in areas of normal-appearing white matter were significantly higher than those in corresponding white matter regions in healthy controls (P < 0.0001). The tissue
sodium concentration value averaged over lesions and over regions of normal-appearing white and grey matter was positively associated with T(2)-weighted (P < or = 0.001 for all) and T(1)-weighted (P < or = 0.006 for all) lesion volumes. In patients, only the tissue
sodium concentration value averaged over regions of normal-appearing grey matter was negatively associated with the normalized grey matter volume (P = 0.0009). Finally, the expanded disability status scale score showed a mild, positive association with the mean tissue
sodium concentration value in chronic lesions (P = 0.002), in regions of normal-appearing white matter (P = 0.004) and normal-appearing grey matter (P = 0.002). This study shows the feasibility of using in vivo
sodium magnetic resonance imaging at 3 T in patients with
multiple sclerosis. Our findings suggest that the abnormal values of the tissue
sodium concentration in patients with
relapsing-remitting multiple sclerosis might reflect changes in cellular composition of the lesions and/or changes in cellular and metabolic integrity.
Sodium magnetic resonance imaging has the potential to provide insight into the pathophysiological mechanisms of tissue injury when correlation with histopathology becomes available.