Analysis of the human brain in primary progressive multiple sclerosis with mapping of the spatial distributions using 1H MR spectroscopy and diffusion tensor imaging

Primary progressive multiple sclerosis (ppMS; n=4) patients and controls (n=4) were examined by 1H magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in order to map choline (Cho), creatine and N-acetylaspartate (NAA), the fractional anisotropy (FA) and the apparent diffusion constant (ADC). After chemical shift imaging (point-resolved spectroscopy, repetition time/echo time 1,500 ms/135 ms) of a supraventricular volume of interest of 8x8x2 cm(3) (64 voxels) MRS peak areas were matched to the results of DTI for the corresponding volume elements. Mean FA and NAA values were reduced in the ppMS patients (P < 0.01, both) and the ADC increased (P < 0.02). The spatial distribution of NAA showed strong correlation to ADC in both ppMS patients and controls (r =-0.74 and r= -0.70; P < 0.00001, both), and weaker correlations to FA (r=0.49 and r=0.41; P < 0.00001, all). FA and ADC also correlated significantly with Cho in patients and controls (P < 0.00001, all). The relationship of Cho and NAA to the ADC and the FA and thus to the content of neuronal structures suggests that these metabolite signals essentially originate from axons (NAA) and the myelin sheath (Cho). This is of interest in view of previous reports in which Cho increases were associated with demyelination and the subsequent breakdown of neurons.