Whole-brain N-acetylaspartate quantification as a biomarker for diffuse neurodegeneration

1H-MRS is a noninvasive, quantitative imaging modality often added to increase the specificity of MRI. It provides information about the underlying biochemistry via the levels of several detectable neuro-metabolites. Key amongst these is the N-acetylaspartate (NAA), which is widely regarded as a marker for neuronal health and viability and, therefore, ideally suited for probing the biochemistry of neurological disorders. Unfortunately, most brain 1H-MRS studies to date have employed small volumes-of-interest that must be placed away from the skull to avoid contamination from bone marrow and subcutaneous lipids. Consequently, they (i) miss most of the cortical gray matter, (ii) account for less than 10% of the brain volume; and (iii) are subject to gross repositioning errors in serial studies. To overcome these issues we employ a procedure designed to measure the global concentration of NAA in the whole brain (WBNAA). It has been shown in cross-sectional studies to be a sensitive marker for the diffuse neurodegeneration that is characteristic in Multiple Sclerosis (MS). The specific aims of this study, therefore, are to establish that WBNAA: (1) is a "good" surrogate marker, i.e., insensitive to instrumental confounds; (2) is, as expected, temporally stable in normal, young adults; and (3) exhibits a decrease in MS which is significant and, consequently, potentially clinically meaningful.