Magnetic resonance elastography (MRE) has been introduced in clinical practice as a possible surrogate for mechanical palpation, but its application to study the human brain in vivo has been limited by low spatial resolution and the complexity of the inverse problem associated with biomechanical property estimation. Here, we report significant improvements in brain MRE data acquisition by reporting images with high spatial resolution and signal-to-noise ratio as quantified by octahedral shear strain metrics. Specifically, we have developed a sequence for brain MRE based on multishot, variable-density spiral imaging, and three-dimensional displacement acquisition and implemented a correction scheme for any resulting phase errors. A Rayleigh damped model of brain tissue mechanics was adopted to represent the parenchyma and was integrated via a finite element-based iterative inversion algorithm. A multiresolution phantom study demonstrates the need for obtaining high-resolution MRE data when estimating focal mechanical properties. Measurements on three healthy volunteers demonstrate satisfactory resolution of gray and white matter, and mechanical heterogeneities correspond well with white matter histoarchitecture. Together, these advances enable MRE scans that result in high-fidelity, spatially resolved estimates of in vivo brain tissue mechanical properties, improving upon lower resolution MRE brain studies that only report volume averaged stiffness values. Magn Reson Med 70:404–412, 2013. © 2012 Wiley Periodicals, Inc.