A quantitative study of water diffusion in multiple sclerosis lesions and normal-appearing white matter using echo-planar imaging

Objectives: We used an optimized echo-planar pulse sequence for isotropically weighted diffusion imaging (1) to measure mean diffusivity ((D) over bar) in lesions and normal-appearing white matter (NAWM) in the entire brain from patients with mildly disabling relapsing remitting multiple sclerosis (MSS, (2) to compare the (D) over bar. of NAWM from patients with that of white matter from normal controls, (3) to evaluate whether lesions classified on the basis of their appearance on enhanced T1-weighted scans have different (D) over bar, and (4) to investigate the relationship between diffusion changes in lesions and NAWM. Methods: Dual-echo and diffusion-weighted scans were obtained from 35 patients with relapsing-remitting MS and 24 sex- and age-matched normal controls. Postcontrast T1-weighted images were also obtained from the patients. After creating (D) over bar maps and image coregistration, values were measured for MS lesions larger than 5 mm and for 22 NAWM areas from each subject. Results: All NAWM areas studied had significantly higher (D) over bar in patients than in controls. A total of 173 lesions were identified on the dual-echo scans from patients. The average (D) over bar for these lesions was significantly higher than that of NAWM. Twenty-two lesions were enhancing and 60 were classified as T1-hypointense. No significant difference in (D) over bar values was found between enhancing and nonenhancing lesions, while the average (D) over bar of T1-hypointense lesions was significantly higher than the average (D) over bar of T1-isointense lesions. There was no significant correlation between the average (D) over bar in lesions and NAWM. Conclusions: 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.