Vascular-space-occupancy (VASO) MRI exploits the difference between blood and tissue T1 to null blood signal and measure cerebral blood volume changes using the residual tissue signal. VASO imaging is more difficult at higher field because of sensitivity loss due to the convergence of tissue and blood T1 values and increased contamination from blood-oxygenation-level-dependent (BOLD) effects. In addition, compared to 3T, 7T MRI suffers from increased geometrical distortions, e.g., when using echo-planar-imaging, and from increased power deposition, the latter especially problematic for the spin-echo-train sequences commonly used for VASO MRI. Third, non-steady-state blood spin effects become substantial at 7T when only a head coil is available for radiofrequency transmit. In this study, the magnetization-transfer-enhanced-VASO approach was applied to maximize tissue-blood signal difference, which boosted signal-to-noise ratio by 149% ± 13% (n = 7) compared to VASO. Second, a 3D fast gradient-echo sequence with low flip-angle (7°) and short echo-time (1.8 ms) was used to minimize the BOLD effect and to reduce image distortion and power deposition. Finally, a magnetization-reset technique was combined with a motion-sensitized-driven-equilibrium approach to suppress three types of non-steady-state spins. Our initial functional MRI results in normal human brains at 7T with this optimized VASO sequence showed better signal-to-noise ratio than at 3T. Magn Reson Med 69:1003–1013, 2013. © 2012 Wiley Periodicals, Inc.