Tissue damage within normal appearing white matter in early multiple sclerosis: assessment by the ratio of T1-and T2-weighted MR image intensity

Histopathological and magnetic resonance imaging (MRI) studies have shown white matter (WM) damage in early stages of multiple sclerosis (MS) beyond the apparent T2-hyperintense lesions. These changes in normal appearing WM (NAWM) are important with regard to the clinical picture and prognosis. However, the detection of changes within NAWM has so far required special imaging techniques commonly not available in clinical routine and, hence, at large scale. The purpose of this study was to detect MS-related damage of NAWM by conventional MRI. As, within NAWM, the myelin content mainly drives the T1-weighted (T1w) signal, we scaled it by the T2w signal. We tested the hypothesis that the mean T1w/T2w ratio of NAWM is decreased in MS compared to healthy controls (HC) and that it correlates with clinical measures. We developed a pipeline to determine the individual mean values of this ratio within NAWM. We studied 244 patients in early disease stages of MS (mean age 37 +/- A 10 years, mean disease duration 3.1 +/- A 2.3, Expanded Disability Status Scale 1.3 +/- A 1), and 78 HC (mean age 31 +/- A 8 years). Compared to HC, the mean T1w/T2w ratio was lowered in the patient group (P < 0.001). The difference remained significant after restricting the analysis to patients with a disease duration of 5 years or less and without disease modifying drugs. Our measures also correlated with clinical scores. We believe that the mean T1w/T2w ratio is a promising candidate to assess MS-related tissue damage within NAWM at large scale.