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Magnetic resonance elastography (MRE) has shown promise in noninvasively capturing changes in mechanical properties of the human brain caused by neurodegenerative conditions. MRE involves vibrating the brain to generate shear waves, imaging those waves with MRI, and solving an inverse problem to determine mechanical properties. Despite the known anisotropic nature of brain tissue, the inverse problem in brain MRE is based on an isotropic mechanical model. In this study, distinct wave patterns are generated in the brain through the use of multiple excitation directions in order to characterize the potential impact of anisotropic tissue mechanics on isotropic inversion methods. Isotropic inversions of two unique displacement fields result in mechanical property maps that vary locally in areas of highly aligned white matter. Investigation of the corpus callosum, corona radiata, and superior longitudinal fasciculus, three highly ordered white matter tracts, revealed differences in estimated properties between excitations of up to 33%. Using diffusion tensor imaging to identify dominant fiber orientation of bundles, relationships between estimated isotropic properties and shear asymmetry are revealed. This study has implications for future isotropic and anisotropic MRE studies of white matter tracts in the human brain., (Copyright © 2016 Elsevier Ltd. All rights reserved.)