Effect of N-acetylaspartic acid on the diffusion coefficient of water: a proton magnetic resonance phantom method for measurement of osmolyte-obligated water.

N-acetyl-L-aspartic acid (NAA) is an amino acid present in the vertebrate brain that is synthesized and stored primarily in neurons, although it cannot be hydrolyzed in these cells. Nonetheless, neuronal NAA is dynamic and turns over more than once each day by cycling, via extracellular fluids (ECF), between neurons and catabolic compartments in oligodendrocytes. One important role of the NAA intercompartmental cycle appears to be osmoregulatory, and in this role it may be the primary mechanism for the removal of metabolic water, against a water gradient, from myelinated neurons. However, the number of water molecules that might be cotransported to ECF per NAA molecule released is as yet unclear. In this investigation, using a proton nuclear magnetic resonance method and diffusion measurements at two magnetic field strengths on water and NAA phantoms in vitro, the effect of NAA on the diffusion coefficient of water has been measured, and a ratio (K) of obligated water molecules per molecule of NAA has been determined. For NAA measured at 100mM and 3 Tesla K=24 and at 7 Tesla K=14. Based on these results, apparent K(NAA) varies inversely with field strength, and with a computed field strength factor of 2.55mmol water/unit Tesla, K(NAA) in the absence of any applied magnetic field strength would be 32.