The interrelationship between impulsive head loading parameters and either the presence and/or severity of diffuse axonal damage has not been fully developed. In this investigation, an experimental model of diffuse axonal injury is used to explore the relationship between intracranial deformations and axonal injury patterns. Surrogate models of the miniature pig skull-brain structure were tested to develop empirical relationships for the regional brain tissue distortion occurring in response to an impulsive head rotation. The magnitude and direction of principal strains measured in a mid-coronal plane of the physical model, when merged with information on the axonal trajectories in this plane, were used to predict areas most prone to mechanically mediated axonal damage. Histological evidence of axonal injury from a series of animal experiments demonstrate that most predicted regions of axonal injury exhibit signs of axonal damage, while other regions of the brain experiencing smaller strains do not. This study represents a first approach towards merging biomechanical data with neuroanatomic information to relate the distribution and severity of axonal injury with specific macroscopic head motion parameters.