Proton MR spectroscopy with metabolite-nulling reveals elevated macromolecules in acute multiple sclerosis

Proton magnetic resonance spectroscopy has shown elevated signals in the sp ectral region of lipids in acute multiple sclerosis lesions. The metabolite -nulling technique allows the separation of macromolecules from other metab olites, such as lactate, N-acetyl-aspartate, creatine, choline and myo-inos itol. Using this technique in studies on multiple sclerosis patients, we we re able to differentiate macromolecules biochemically in acute and chronic multiple sclerosis lesions. Ten patients with acute, contrast-enhancing mul tiple sclerosis lesions, 10 patients with chronic lesions and 10 healthy co ntrol subjects were investigated with a 1.5 T whole body system, using a st imulated echo acquisition mode (STEAM) sequence with metabolite-nulling and outer volume saturation. Metabolites and macromolecules were quantitated a bsolutely. The 0.9 and 1.3 parts per million (p.p.m.) resonances of the mac romolecules were significantly elevated in acute lesions compared with chro nic lesions and healthy controls (P < 0.001 for 0.9 p.p.m., P < 0.05 for 1. 3 p.p.m.), The macromolecular resonances at 2.1 and 3.0 p.p.m. in acute and chronic lesions were normal, N-acetyl-aspartate was significantly reduced in acute and chronic lesions compared with controls (P < 0.05 and P < 0.01, respectively). Choline was significantly elevated in acute lesions compare d with controls (P < 0.05). Up to now, elevated resonances at 0.9 and 1.3 p .p.m. in acute lesions have been interpreted as lipids. In metabolite-nulle d spectra, the macromolecular resonances did not fit those of lipids and mi ght have been due to proteins or polypeptides containing the amino acids al anine, threonine, valine, leucine and isoleucine. These account for <simila r to>40% of the amino acids of myelin proteolipid protein and for similar t o 20% of myelin basic protein. The increased macromolecular resonances at 0 .9 and 1.3 p.p.m. may be interpreted as biochemical markers of myelin fragm ents and may be used as reliable markers of acute multiple sclerosis lesion s as they provide clear discrimination among acute and chronic lesions and controls.