Choline is increased in pre-lesional normal appearing white matter in multiple sclerosis

Abstract.Objective: Our aim was to determine if the resonance intensity of choline-containing compounds (Cho) measured using proton magnetic resonance spectroscopy (MRS) was increased in pre-lesional normal appearing white matter (NAWM) in patients with multiple sclerosis (MS) relative to NAWM that remained stable in subsequent scans. Background: The Cho peak in MR spectra is associated with membrane phospholipids and increases in acute MS plaques, possibly even before the appearance of MRI-visible MS lesions. Methods: Three combined proton MRI and MRS imaging examinations of the corpus callosum and adjacent periventricular white matter were performed on 12 MS patients at intervals of 6 months. Proton density (PD) images were visually matched across 3 time points and the lesion volume in each voxel of the volume of interest was determined. The voxels were subdivided into four groups based on the presence or absence of lesion at baseline and change or no change in lesion volume on the subsequent scan. Results: We found a significantly higher baseline Cho/Creatine (Cr) ratio in NAWM voxels that displayed MRI visible lesions 6 months later than NAWM voxels that remained unchanged (1.57 ± 0.30 and 1.37 ± 0.33, respectively, p < 0.001). The 12-month interval data revealed similar pre-lesional elevated Cho/Cr, (1.51 ± 0.29 versus 1.39 ± 0.32, p = 0.009). Voxels that contained lesion at baseline and increased in lesion volume at 6 months also showed a significantly higher Cho/Cr ratio than those whose lesion volume did not change (1.60 ± 0.32 and 1.49 ± 0.36, respectively, p = 0.043). Conclusions: The results of this study are consistent with focal pre-lesional myelin membrane pathology in the NAWM at least 12 months before lesions become visible on conventional MRI. This could reflect altered myelin chemistry or the presence of inflammation as seen in experimental allergic encephalomyelitis.