Challenges and perspectives of functional sodium imaging (fNaI)

Brain function has been investigated via the blood oxygenation level dependent (BOLD) effect using magnetic resonance imaging (MRI) for the past decades. Advances in sodium imaging offer the unique chance to access signal changes directly linked to sodium ion (23Na) flux across the cell membrane, which generates action potentials, hence signal transmission in the brain. During this process, sodium ions (23Na) transiently accumulate in the intracellular space. Here we show that functional sodium imaging (fNaI) at 3T is sensitive to sodium ion (23Na) concentration changes during finger tapping, which can be quantified in grey and white matter regions key to motor function. For the first time, we measured a sodium ion (23Na) concentration change of 0.54 mmol/l in the ipsilateral cerebellum, 0.46 mmol/l in the contralateral primary motor cortex, 0.27 mmol/l in the corpus callosum and -11 mmol/l in the ipsilateral primary motor cortex, suggesting that fNaI is sensitive to both excitation and inhibition and to sodium concentration changes in white matter, where BOLD fails. Initial calculations from neuronal ATP consumption can explain 10% of the experimental change, with the remainder potentially reflecting blood volume changes. An open issue persists in the role of the glymphatic system in maintaining homeostasis and volume distributions during neuronal activity. Development of realistic models of tissue function will be essential to understand the mechanisms of such changes and contribute to meeting the overarching challenge of measuring neuronal activity in vivo.