Macroscopic and microscopic assessments of disease burden by MRI in multiple sclerosis: relationship to clinical parameters.

We have evaluated macroscopic white matter abnormalities (visible lesions) together with microscopic abnormalities in the normal appearing white matter (NAWM) of patients with multiple sclerosis (MS) to determine their relative contributions to the development of disability. The total visible lesion volume (TLV) was computed as a measure macroscopic changes, whereas both texture analysis and T2 were used as possible indicators of diffuse disease in the NAWM. Dual echo T2-weighted SE images were obtained from 41 patients with definite MS: 10 primary progressive (PP), 11 secondary progressive (SP), 10 benign (BE), 10 early relapsing remitting (ERR), as well as from 10 healthy controls. Calculation of T2 and texture parameters were performed in a region of frontal NAWM of patients and controls. The TLV of each patient was measured using a semiautomated lesion detection program. No significant differences were found between the controls and the patients for all texture parameters examined. However, NAWM T2 was longer in the patients than in the controls (P = .02). Mean TLV was highest for SP and lowest for BE and ERR patients. A significant correlation was found between TLV and EDSS (P < .01) but not between NAWM T2 or texture and expanded disability status score (EDSS). Our study suggest that: (a) diffuse changes are present in NAWM, (b) texture analysis is unable to detect any subtle structure in the NAWM abnormalities, possibly because of the limited image resolution; (c) in the development of disability in MS, macroscopic lesions are more important than microscopic abnormalities in the NAWM.