Finite element modeling (FEM) is frequently used to study the biomechanical effects of traumatic brain injury (TBI). Utility of these models in predicting tissue injury depends on close correspondence between calculated mechanical response parameters and those actually occurring in tissue, as well as the establishment of accurate thresholds of tissue injury for each of these parameters. We developed a three-dimensional FEM of the neonatal piglet brain and used it to predict the spatial distributions of tissue strains during horizontal, coronal and sagittal rotations of the head in order to evaluate our hypothesis that the spatial pattern of axonal injury is attributed to differences in regional tissue strains. The maximum principal strains and the white matter tract (WMT) oriented strains were compared. Diffusion tensor imaging (DTI) was used to obtain the directions of the axonal fibers in the white matter tracts. While both maximum principal strains and the white matter tract oriented strains are correlated with regional axonal injury, WMT-oriented strain had a higher predictive power (WMT strain Receiver Operating Characteristic (ROC) area under curve = 0.848; Max Principal Strain ROC area under curve=0.807). The strain thresholds predicting axonal injury were 4.7% for WMT strain and 39.9% for Max Principal Strain. © 2012 IEEE.