Relapsing-Remitting Multiple Sclerosis: Metabolic Abnormality in Nonenhancing Lesions and Normal-appearing White Matter at MR Imaging: Initial Experience

Abstract

To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects. Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher). Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter.