In hyperoxic contrast studies modulated by the blood oxygenation level-dependent effect, it is often assumed that hyperoxia is a purely intravascular, positive contrast agent in T 2 *-weighted images, and the effects that are not due to blood oxygenation level-dependent contrast are small enough to be ignored. In this study, this assumption is re-evaluated and non-blood oxygenation level-dependent effects in T 2 *-weighted hyperoxic contrast studies of the human brain were characterized. We observed significant negative signal changes in T 2 *-weighted images in the frontal lobes; B 0 maps suggest that this effect was primarily due to increased intravoxel dephasing from increased static field inhomogeneity due to susceptibility changes from oxygen in and around the upper airway. These static field effects were shown to scale with magnetic field strength. Signal changes observed around the brain periphery and in the ventricles suggest the effect of image distortions from oxygen-induced bulk B 0 shifts, along with a possible contribution from decreased T 2 * due to oxygen dissolved in the cerebrospinal fluid. Reducing the concentration of inhaled oxygen was shown to mitigate negative contrast of molecular oxygen due to these effects, while still maintaining sufficient blood oxygenation level-dependent contrast to produce accurate measurements of cerebral blood volume. Magn Reson Med 66:794-801,

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