PURPOSE: To investigate intercenter agreement of brain volume (change) measurement in multiple sclerosis (MS) using structural image evaluation using normalization of atrophy (SIENA) and the cross-sectional version of SIENA (SIENAX) with additional manual editing to correct for inadequate brain extraction. MATERIALS AND METHODS: Baseline and follow-up T1-weighted MR images of 20 MS patients were dispatched to five centers. Each center performed fully-automated and manually-edited analyses for SIENAX, yielding normalized brain volume (NBV), and SIENA, yielding percentage brain volume change (PBVC). Intercenter agreement was assessed with the concordance correlation coefficient (CCC). RESULTS: Intercenter agreement was perfect for fully automated NBV and PBVC (both CCC = 1.0), and remained substantial upon manual editing (CCC = 0.94 for NBV, CCC = 0.95 for PBVC). Mean NBV values for each center decreased significantly after manual editing (overall mean NBV = 1605.3 cm(3) vs. 1651.1 cm(3) without manual editing; t = -4.58, P