In patients with cerebral small vessel disease (SVD) diffusion tensor imaging (DTI) is sensitive to white matter damage and correlates better with cognitive function than conventional imaging. It has been proposed as a surrogate marker for treatment trials. However, the pathological changes underlying DTI are not known. The purpose of this study was to use magnetic resonance spectroscopy (MRS) to determine the pathological changes underlying DTI abnormalities in a range of patients from asymptomatic white matter hyperintensities to symptomatic cerebral SVD. 29 SVD patients, 63 hypertensive subjects, and 42 normotensive controls were recruited. The relationship between the DTI and MRS parameters in the centrum semiovale white matter was determined. There was a significant reduction in N-acetylaspartate (NAA; 2.067 +/- 0.042 vs 2.299 +/- 0.029 and 2.315 +/- 0.036, P = 9 x 10(-6)) and increase in mean diffusivity (mm2/s x 10(-3); 0.942 +/- 0.123 vs 0.822 +/- 0.064 and 0.792 +/- 0.057, P = 1 x 10(-8)) in symptomatic SVD patients compared with the other two groups. DTI parameters correlated with NAA in all three groups, in a graded manner depending on severity of disease (r -SVD -0.827, hypertensive subjects -0.457, controls -0.317). NAA is a marker of axonal loss/dysfunction. These findings are consistent with axonal loss/dysfunction being the principal process causing the DTI changes found in cerebral SVD and ageing.
(c) 2008 Wiley-Liss, Inc.