Relationship between fractional anisotropy of cerebral white matter and metabolite concentrations measured using (1)H magnetic resonance spectroscopy in healthy adults

Fractional anisotropy (FA) of water diffusion in cerebral white matter (WM), derived from diffusion tensor imaging (DTI), is a sensitive index of microscopic WM integrity. Physiological and metabolic factors that explain intersubject variability in FA values were evaluated in two cohorts of healthy adults of different age spans (N=65, range: 28-50years; and N=25, age=66.6±6.2, range: 57-80years). Single voxel magnetic resonance spectroscopy (MRS) was used to measure N-acetylaspartate (NAA), total choline-containing compounds, and total creatine, bilaterally in an associative WM tract: anterior corona radiata (ACR). FA values were calculated for the underlying, proximal and two distal WM regions. Two-stage regression analysis was used to calculate the proportion of variability in FA values explained by spectroscopy measurements, at the first stage, and subject's age, at the second stage. WM NAA concentration explained 23% and 66% of intersubject variability (p<0.001) in the FA of the underlying WM in the younger and older cohorts, respectively. WM NAA concentration also explained a significant proportion of variability in FA of the genu of corpus callosum (CC), a proximal WM tract where some of the fibers contained within the spectroscopic voxel decussate. NAA concentrations also explained a significant proportion of variability in the FA values in the splenium of CC, a distal WM tract that also carries associative fibers, in both cohorts. These results suggest that MRS measurements explained a significant proportion of variability in FA values in both proximal and distal WM tracts that carry similar fiber-types.