Introduction: MS diagnosis is increasingly reliant on MR but routine imaging is not specific for MS. New MR modalities like spectroscopy might add to the specificity of diagnosis and could potentially identify new biomarkers.

Methods: One-dimensional (1D) and two-dimensional (2D) localised correlation spectroscopy (L-COSY) MRS was acquired from the posterior cingulate gyrus (PCG) using a 3T Prisma MRI scanner. MRS was performed on 11 RRMS participants receiving immunomodulatory treatment (n=8) or no treatment (n=3) with a mean EDSS of 2.0. Comparisons were made with a healthy age and gender-matched control group (n=8). Data was acquired from a 3x3x3 cm3 voxel. 1D profiles were analysed with LCModel (v6.2-2B) using water normalization. Felix 2007 software was used for the processing and analysis of the 2D L-COSY data. The creatine methyl resonance (3.02-3.02ppm) was used as the internal chemical shift reference and cross-peak volume ratios were normalized to water. Average peak volumes were calculated for each assigned metabolite and compared using a Mann-Whitney test (non-normal distribution) using Stata ADDIN EN.CITE StataCorp2013233(StataCorp 2013)2332339StataCorpStata Statistical Software: Release 13Release 132013TXCollege Station(StataCorp 2013).

Results: L-COSY identified two metabolites, not detectable by 1D MRS, a diagonal peak at 1.33ppm and a cross peak at 3.8-3.33ppm, which can be tentatively assigned to glucose and/or glycerol. Compared to healthy controls the MS group had 76% (P=.032) increase in the 1.33ppm peak and 22% increase (P=.02) in glycerol/glucose. With 1D spectroscopy, we identified a statistically significant increase in aspartate (+8%, P=0.013), N-acetylaspartate (+2%, P=0.048), and lipid+macromolecues (+7%, P=0.04) in MS patients compared to control.

Conclusion: In vivo spectroscopy has the potential to play an important role in biomarker discovery in MS disease. L-COSY is adding significantly to 1D spectroscopy in identifying biochemical changes in the central nervous system of MS patients.