Shift reagent enhanced concurrent 23Na and 1H magnetic resonance spectroscopic studies of transcellular sodium distribution in the dog brain in vivo

Abstract
The intracellular to extracellular sodium distribution is one of the primary determinants of action potentials necessary for the electrical function of organs such as brain, heart and skeletal muscle. The ability of shift reagent enhanced 23Na MRS to directly measure the intracellular and extracellular sodium distribution in brain is controversial and centers on the relative contributions of bulk magnetic susceptibility and hyper-fine interactions to the observed chemical shifts. In this study, infusion of dysprosium (111) triethylenetetraminehexacetate (Dy(TTHA)−3), resulted in a 23Na MRS spectrum of dog brain with two well resolved peaks at 9 and 0.4 ppm. The 9 ppm peak corresponded to the resonance seen in aspirated blood. After disruption of the blood brain barrier, the single peak at 0.4 ppm split into two peaks at 3 and 0 ppm. The ability of Dy-(lTHIA)−3 enhanced 23Na MRS to follow global changes in brain sodium distribution was tested during cardiac arrest. The expected rapid Na influx into the intracellular space produced a marked decrease in the 3 ppm signal and a parallel increase in the 0 ppm peak. This is consistent with the assignment of the 3 ppm peak as interstitial sodium and the 0 ppm peak as intracellular sodium.