Keywords: Multiple Sclerosis, Segmentation, Quantification, Water ReferencingA current standard practice in proton magnetic resonance spectroscopy (1H-MRS) uses water as an internal reference for absolute metabolite quantification. We investigate how apparent metabolite concentrations might be affected by tissue-level changes, specifically multiple sclerosis lesions, via water versus creatine referencing in voxels considered normal-appearing at time of scan. Our results suggest that multiple possible routes of confound by hidden lesions on metabolite quantification in even normal-appearing tissue should be considered when applying internal water referencing to 1H-MRS studies in cohorts with multiple sclerosis.
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