To investigate the evolution of cellular compartment fractions in white matter lesions in multiple sclerosis (MS) using fitting of a three-component model to T₂^* relaxation decay curves at 7T.Based on the identification of enhancing white matter lesions in scheduled examinations at 3T, five women with relapsing-remitting MS (age range 33-59 years, and average age 42 years) were scanned at 7T. Follow-up scans were performed after approximately 3, 6, and 12 months. The multi-gradient-echo data (15 slices, TR 1s, FA 70°) were acquired with isotropic 1.5mm resolution (38 echoes, TEs of 2.3-62.7ms, echo spacing 1.6ms, 5 averages) for mapping the T₂^* decay curves. The slices were parallel to the plane of the anterior and posterior commissure line and captured a section of the corpus callosum. ROIs were chosen in enhancing lesions identified from pre- and post-gadolinium T1-weighted MRI (Fig 1). In addition, control ROIs were chosen in contralateral normal-appearing white matter (NAWM) in homologous locations contralateral to the lesions. Similarly to our previous study,¹ the average complex signal of ROIs was calculated and fitted to a three-component model. Statistical analysis was carried out using ANOVA to investigate the significance of changes in the three-component fitting results among the four scans both for lesions and NAWM.Thirteen enhancing white matter lesions and contralateral NAWM ROIs were analyzed. In the follow-up scans, none of the initially enhancing lesions showed enhancement. The three-component fitting results for lesions and NAWM are shown in Table 1. A_n is the relative amplitude, T₂^*_,n the relaxation time, Δf_n the frequency shift of component n. Components 1, 2, and 3 were assigned to myelin, axonal, and interstitial water, respectively.^{2, 3} For the analyses of lesions, the T₂^*_,1 and Δf₁ were fixed at values from contralateral NAWM, as the myelin water signal in lesions proved to be too small to determine independently. In lesions, the amount of myelin water (A₁) was found to be significantly decreased relative to the contralateral NAWM (Table 1), suggesting demyelination.⁴ The accompanying increased T₂^* of axonal and interstitial water (T₂^*_,2 and T₂^*_,3), and decreased small frequency shift of axonal water (Δf₂) are also consistent with myelin loss.3 Significant decreases in T₂^* of axonal water (p=0.023) and interstitial water (p=0.003) were found in lesions among the four scans (Fig 2a and 2b), especially when comparing the 3-month follow-up scan with the baseline, which might indicate the progression of remyelination. However, increases in the frequency shift of axonal water (Δf₂) and myelin water fraction (A₁), which would support this remyelination hypothesis, were not significant. In NAWM, no significant changes were observed across the four scans.The mechanisms underlying the progression of MS and the relationship to pathology are still unclear. The microcompartment-specific T₂^* relaxation values of initially enhancing lesions were followed serially on 7T at approximately 3, 6, and 12 months. The changes over time that we observed in enhancing lesions are consistent with the presence of ongoing remyelination and repair, particularly during the first 3 months. It might support the use of this new technique to study the evolution of cellular compartment fraction in white matter. Moreover, our findings may lead to a better understanding of, and prognostic ability for, this complex disease.