Paramagnetic deoxyhemoglobin in venous blood is a naturally occurring contrast agent for magnetic resonance imaging (MRI). By accentuating the effects of this agent through the use of gradient-echo techniques in high fields, we demonstrate in vivo images of brain microvasculature with image contrast reflecting the blood oxygen level. This blood oxygenation level-dependent (BOLD) contrast follows blood oxygen changes induced by anesthetics, by insulininduced hypoglycemia, and by inhaled gas mixtures that alter metabolic demand or blood flow. The results suggest that BOLD contrast can be used to provide in vivo real-time maps of blood oxygenation in the brain under normal physiological conditions. BOLD contrast adds an additional feature to magnetic resonance imaging and complements other techniques that are attempting to provide positron emission tomographylike measurements related to regional neural activity.Magnetic resonance imaging (MRI) is a widely accepted modality for providing anatomical information. Current research (1) involves extending MRI methods to provide information about biological function, in addition to the concomitant anatomical information. In addition to localized spectroscopy (2) and chemical shift imaging (3) that are applicable to many chemical species, MRI of water protons has been functionally extended to NMR angiography (4), perfusion imaging (5,6), and perfusion imaging enhanced by exogenous contrast agents (7). Since water is by far the predominant molecule in tissue, and since its signal dominates the information content in proton images, one would ideally like to exploit changes in the water signal that arise from physiological events. Except for cases of water movement, such as blood flow, these changes are normally very small.It has previously been demonstrated (8, 9) that the presence of deoxyhemoglobin in blood changes the proton signal from water molecules surrounding a blood vessel in gradientecho MRI, producing blood oxygenation level-dependent (BOLD) contrast. BOLD contrast has its origin in the fact that when normally diamagnetic oxyhemoglobin gives up its oxygen, the resulting deoxyhemoglobin is paramagnetic. The presence of paramagnetic molecules in blood produces a difference in magnetic susceptibility between the blood vessel and the surrounding tissue. This susceptibility difference is "felt" both by the water molecules in the blood and by those in the surrounding tissue, the effect extending significantly beyond the vessel wall. This increase in the number of spins affected by deoxyhemoglobin is a form of amplification. When the susceptibility-induced local field differences exist within an imaging voxel, there is a resultant distribution of shifts in water resonance frequencies. In the gradient-echo method, a phase dispersion of water proton signals is produced at the echo time. This dispersion reduces the signal intensity and the voxel appears dark in the image. These intensity losses, which at high magnetic fields (-4 T) extend significantly beyond the bo...

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