Petracca, Maria (2016) Brain intra- and extra-cellular sodium concentration in multiple sclerosis: a 7 tesla MRI study. [Tesi di dottorato]

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Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide evidence of the feasibility of triple quantum filtered 23Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 healthy controls. Global grey matter and white matter total sodium concentration (respectively P<0.05 and P<0.01), and intracellular sodium concentration (both P<0.001) were higher while grey matter and white matter intracellular sodium volume fraction (indirect measure of extracellular sodium concentration) were lower (respectively P=0.62 and P<0.001) in patients compared with healthy controls. At a brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P<0.05 family-wise error corrected for total sodium concentration, P<0.05 uncorrected for multiple comparisons for intracellular sodium concentration and intracellular sodium volume fraction). Measures of total sodium concentration and intracellular sodium volume fraction, but not measures of intracellular sodium concentration were correlated with T2-weighted and T1-weighted lesion volumes (0.05<P<0.01) and with Expanded Disability Status Scale (P<0.05). The exploration of sodium concentrations in a second cohort of 45 healthy controls disclosed the presence of (i) an association between grey matter volume and intracellular sodium volume fraction but not intracellular sodium concentration and (ii) an age-related decrease in intracellular sodium concentration, independent from brain volumes reduction. In conclusion, our results suggest that while intracellular sodium volume fraction decrease could reflect expansion of extracellular space due to tissue loss, intracellular sodium concentration increase could reflect the presence of neuro-axonal metabolic dysfunction/modifications in neuronal morphology, providing valuable and specific information on tissue microstructure.

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