Functional magnetic resonance imaging of the human brain based on signal enhancement by extravascular protons (SEEP fMRI)

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Abstract
Functional magnetic resonance imaging (fMRI) studies of the human brain were carried out at 3 Tesla to investigate an fMRI contrast mechanism that does not arise from the blood oxygen‐level dependent (BOLD) effect. This contrast mechanism, signal enhancement by extravascular protons (SEEP), involves only proton‐density changes and was recently demonstrated to contribute to fMRI signal changes in the spinal cord. In the present study it is hypothesized that SEEP fMRI can be used to identify areas of neuronal activity in the brain with as much sensitivity and precision as can be achieved with BOLD fMRI. A detailed analysis of the areas of activity, signal intensity time courses, and the contrast‐to‐noise ratio (CNR), is also presented and compared with the BOLD fMRI results. Experiments were carried out with subjects performing a simple finger‐touching task, or observing an alternating checkerboard pattern. Data were acquired using a conventional BOLD fMRI method (gradient‐echo (GE) EPI, TE = 30 ms), a conventional method with reduced BOLD sensitivity (GE‐EPI, TE = 12 ms), and SEEP fMRI (spin‐echo (SE) EPI, TE = 22 ms). The results of this study demonstrate that SEEP fMRI may provide better spatial localization of areas of neuronal activity, and a higher CNR than conventional BOLD fMRI, and has the added benefit of lower sensitivity to field inhomogeneities. Magn Reson Med 49:433–439, 2003.