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There are four conventional magnetic resonance imaging (cMRI) components readily visible to the clinician considering the extent of multiple sclerosis (MS) pathology in individual patients that might be compared with the extent of MRI-defined pathology from group data derived from natural history or clinical trial cohorts. These include: the presence, number and quality of enhancements; the aggregate number and volume of lesions defined on T2-weighted images; the number and volume of T1-weighted hypointense lesions; and net tissue loss or atrophy. Since initially inactive subjects may not contribute much to measuring efficacy over time, many trials rely on a design including an enrichment strategy based on enhancement on one, or sometimes multiple screening MRI studies. Many consider enhancing activity to be an MRI equivalent of clinical relapse. Most studies show little or no correlation between enhancing lesions and composite disability measures at one point in time, or over a few years.