Pathology in patients with clinically isolated syndromes is confined to modest tissue damage in the lesions seen on T2-weighted scans. Severe damage is important for the later development of disability. However, microscopic damage in normal-appearing white matter may be a major contributor to disability in primary progressive MS.

Objective-To assess the feasibility of a new technique based on diVusion anisotropy to segment white and grey matter of the brain. To use this technique to measure the mean diVusivity (D z ) and magnetisation transfer ratio (MTR) of normal appearing white matter (NAWM) and grey matter (NAGM) from patients with multiple sclerosis. Methods-Dual echo turbo spin echo, MT, and diVusion weighted scans of the brain were obtained from 30 patients with multiple sclerosis and 18 sex and age matched healthy controls. After image coregistration and removal of T2 visible lesions, white and grey matter were segmented from 10 supratentorial slices using diVusion anisotropy thresholds. Histograms of the average MTR and D z were created for normal white and grey matter of controls and NAWM and NAGM of patients with multiple sclerosis. Results-All the MTR histogram derived metrics of the NAWM from patients with multiple sclerosis were significantly lower than those of white matter from controls. The peak height of the D z histogram of NAWM from patients with multiple sclerosis was also significantly diVerent from that of normal white matter. The average MTR, the peak location of the MTR histogram, and peak height of the D z histogram of the NAGM of patients with multiple sclerosis were significantly lower than the corresponding quantities of grey matter from controls. Conclusions-A technique was developed for segmenting white and grey matter with the potential for improving the understanding of the pathophysiology of many neurological conditions. Its application to the study of multiple sclerosis confirms the presence of a diVuse tissue damage in the NAWM of these patients and suggests that subtle changes also occur in the NAGM. (J Neurol Neurosurg Psychiatry 2001;70:311-317)

This study shows that diffusion-weighted imaging is able to identify MS lesions with severe tissue disruption. It also shows that widespread increased diffusion can be measured in the NAWM from patients with MS, and suggests that such changes are, at least partially, independent of larger abnormalities.

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This study confirms that, in patients with PPMS, normal-appearing white and gray matter are not spared by disease-related pathological processes, although they are affected to a lesser degree than in patients with SPMS.