White matter tract-oriented deformation predicts traumatic axonal brain injury and reveals rotational direction-specific vulnerabilities.

A systematic correlation between finite element models (FEMs) and histopathology is needed to define deformation thresholds associated with traumatic brain injury (TBI). In this study, a FEM of a transected piglet brain was used to reverse engineer the range of optimal shear moduli for infant (5 days old, 553-658 Pa) and 4-week-old toddler piglet brain (692-811 Pa) from comparisons with measured in situ tissue strains. The more mature brain modulus was found to have significant strain and strain rate dependencies not observed with the infant brain. Age-appropriate FEMs were then used to simulate experimental TBI in infant (n=36) and preadolescent (n=17) piglets undergoing a range of rotational head loads. The experimental animals were evaluated for the presence of clinically significant traumatic axonal injury (TAI), which was then correlated with FEM-calculated measures of overall and white matter tract-oriented tissue deformations, and used to identify the metric with the highest sensitivity and specificity for detecting TAI. The best predictors of TAI were the tract-oriented strain (6-7%), strain rate (38-40 s(-1), and strain times strain rate (1.3-1.8 s(-1) values exceeded by 90% of the brain. These tract-oriented strain and strain rate thresholds for TAI were comparable to those found in isolated axonal stretch studies. Furthermore, we proposed that the higher degree of agreement between tissue distortion aligned with white matter tracts and TAI may be the underlying mechanism responsible for more severe TAI after horizontal and sagittal head rotations in our porcine model of nonimpact TAI than coronal plane rotations.