Magnetic resonance relaxation time mapping in multiple sclerosis: Normal appearing white matter and the “invisible” lesion load

Prolonged T 1 and/or T 2 relaxation times (RT) in the normal appearing white matter (NAWM) of patients with multiple sclerosis (MS) have been attributed either to a diffuse abnormality, or to “small lesions” undetected by visual inspection of conventional MR images. In a comparison of brain slices from five MS patients and five healthy control subjects, we have confirmed that the average T 1 and T 2 RTs obtained from NAWM in patients with MS are significantly prolonged ( p < .04). Quantitative pixel-by-pixel mapping shows that this overall prolongation is due to the averaging of RTs from two subfractions of NAWM. In all patients a proportion (average 54% for T 1 and 63% for T 2) of the total white matter pixel sample from each MR brain slice had RT values indistinguishable from those found in the white matter of matched healthy control subjects (i.e., “normal normal appearing white matter”, NNAWM). Scattered throughout the NAWM were multiple small areas, often of only one or two pixels, with abnormal RT values. These lesions, which were revealed only by pixel-by-pixel mapping of RT, made up a significant proportion (average 47% for T 1 or 57% for T 2 estimates) of the total (visible plus “invisible”) lesion load per slice, and of the NAWM (average 36% for T 1, 27% for T 2), with wide interpatient variability. Further studies of these minute lesions are required to determine their total volume in the brain, their precise nature, evolution and relevance to the functional deficit in MS.