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The present study applied T₂- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O₂), after 16 hours passive exposure to normobaric hypoxia (12% O₂) corresponding to a simulated altitude of 4,500 m and after 6 hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during hypoxia and corresponding headache scores were markedly elevated (P < 0.05 versus non-AMS). Hypoxia was associated with a mild increase in brain volume (+ 7.0 ± 4.8 ml, P < 0.05 versus preexposure baseline) that resolved during normoxic recovery. Hypoxia was also associated with an increased T₂ relaxation time (T₂rt) and a general trend toward an increased apparent diffusion coefficient (ADC). During the normoxic …