Objectives: To quantify, using diffusion tensor imaging (DTI), the tissue d
amage in lesions and normal-appearing white matter (NAWM) from a large coho
rt of patients with MS and to investigate the magnitude of the correlation
between DTI-derived metrics and clinical disability. Methods: Dual-echo and
DTI scans were obtained from 78 patients with relapsing-remitting, seconda
ry progressive, or primary progressive MS and from 20 normal control partic
ipants. Post-contrast T1-weighted images were also obtained from the patien
ts. After creating mean diffusivity ((D) over bar) and fractional anisotrop
y (FA) images and image coregistration, (D) over bar and FA values were mea
sured for 4846 lesions (3207 nonenhancing T1-isointense, 1511 nonenhancing
T1-hypointense, and 128 enhancing), 497 NAWM areas from patients, and 160 w
hite matter areas from the controls. Results: The average lesion (D) over b
ar was higher and the average lesion FA was lower than the corresponding qu
antities of the NAWM (p < 0.001). The <(D)over bar> values of enhancing and
nonenhancing lesions were not different, whereas enhancing lesions had low
er FA (p < 0.001). T1-hypointense lesions had higher <(D)over bar> and lowe
r FA than T1-isointense lesions (p < 0.001). NAWM of patients had higher <(
D)over bar> and lower FA than white matter of controls (p = 0.01). Signific
ant correlations were found between T1 and T2 lesion volume and (D) over ba
r and FA of lesions and NAWM. In the overall patient sample, a moderate cor
relation was also found between lesion (D) over bar and the Expanded Disabi
lity Status Scale score (r = 0.28, p = 0.01). However, the r value of this
correlation was 0.48 in patients with secondary progressive MS, whose disab
ility was also correlated with average lesion FA (r = -0.50). Conclusions:
The results of this study show that DTI is able to identify MS lesions with
severe tissue damage and to detect changes in the NAWM. They also indicate
that DTI-derived measures are correlated with clinical disability, especia
lly in patients with secondary progressive MS, thus suggesting a role for D
TI in monitoring advanced phases of the disease.