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The traditional primary imaging outcomes used in Phase 2 MS trials, new or enhancing white matter lesions on MRI, target the effects of peripheral inflammation, but the widespread inflammation behind a mostly closed blood-brain barrier is not captured. This review discusses several emerging imaging technologies that could be used as surrogate markers of compartmentalized inflammation, targeting chronic active lesions, meningeal inflammation, and innate immune activation within the normal-appearing white matter and gray matter. 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