Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis:: evidence for distinct mechanisms of lesion genesis?

It is generally believed that most T-2-weighted (T-2) lesions in the central white matter of patients with multiple sclerosis begin with a variable period of T-1-weighted (T-1) gadolinium (Gd) enhancement and that T1 Gd-enhancing and T-2 lesions represent stages of a single pathological process. Lesion probability maps can be used to test this hypothesis by providing a quantitative description of the spatial distribution of these two types of lesions across a patient population. The simplest prediction of this hypothesis would be that the spatial distributions of T-1 Gd-enhancing and T-2 lesions are identical. We generated T-1 Gd-enhancing and T-2 lesion probability maps from 19 patients with relapsing-remitting multiple sclerosis, There was a significantly higher probability (P = 0.001) for T-2 lesions to be found in the central relative to the peripheral white matter (risk ratio 4.5), although the relative distribution of T-1 Gd-enhancing lesions was not significantly different (P = 0.7) between central and peripheral white matter regions (risk ratio 0.6). Longitudinal data on the same population were used to demonstrate a similar distribution asymmetry between new T-1 Gd-enhancing and new T-2 lesions that developed over the course of 1 year. Alternative hypotheses to explain this observation were tested. We found no spatial difference in the likelihood of development of persistent T-2 lesions following T-1 Gd enhancement. The relative distribution of T-1 Gd-enhancing lesions was shown to be independent of the dose of Gd contrast agent and the frequency of scanning. Our findings suggest that a proportion of the periventricular T-2 lesion volume may arise from mechanisms other than those associated with early breakdown of the blood-brain barrier leading to T-1 Gd enhancement.