Sources of phase changes in BOLD and CBV-weighted fMRI.

Phase changes in blood oxygenation-level dependent (BOLD) fMRI have been observed in humans; however, their exact origin has not yet been fully elucidated. To investigate this issue, we acquired gradient-echo (GE) BOLD and cerebral blood volume (CBV)-weighted fMRI data in anesthetized cats during visual stimulation at 4.7T and 9.4T, before and after injection of a superparamagnetic contrast agent (monocrystalline iron oxide nanoparticles, MION), respectively. In BOLD fMRI, large positive changes in both magnitude and phase were observed predominantly in the cortical surface area, where the large draining veins reside. In CBV-weighted fMRI, large negative changes in both magnitude and phase were detected mainly in the middle cortical area, where the greatest CBV change takes place. Additionally, the phase change was temporally correlated with the magnitude response and was linearly dependent on the echo time (TE), which cannot be explained by the intravascular (IV) contribution and functional temperature change. Phase changes with the opposite polarity were also observed in the regions around the dominant phase changes. These phase changes can be explained by the application of the "Lorentz sphere" theory in the presence of relevant activation-induced changes in vessels. The volume-averaged magnetization and its demagnetization are the main sources of fMRI signal phase change.