Multinuclear MRI to disentangle intracellular sodium concentration and extracellular volume fraction in breast cancer

The purpose of this work was to develop a novel method to disentangle the intra- and extracellular components of the total sodium concentration (TSC) in breast cancer from a combination of proton ([Formula: see text] H) and sodium ([Formula: see text] ) magnetic resonance imaging (MRI) measurements. To do so, TSC is expressed as function of the intracellular sodium concentration ([Formula: see text] ), extracellular volume fraction (ECV) and the water fraction (WF) based on a three-compartment model of the tissue. TSC is measured from [Formula: see text] MRI, ECV is calculated from baseline and post-contrast [Formula: see text] H [Formula: see text] maps, while WF is measured with a [Formula: see text] H chemical shift technique. [Formula: see text] is then extrapolated from the model. Proof-of-concept was demonstrated in three healthy subjects and two patients with triple negative breast cancer. In both patients, TSC was two to threefold higher in the tumor than in normal tissue. This alteration mainly resulted from increased [Formula: see text] ([Formula: see text] 30 mM), which was [Formula: see text] 130% greater than in healthy conditions (10–15 mM) while the ECV was within the expected range of physiological values (0.2–0.25). Multinuclear MRI shows promise for disentangling [Formula: see text] and ECV by taking advantage of complementary [Formula: see text] H and [Formula: see text] measurements.