Multi-Scale White Matter Tract Embedded Brain Finite Element Model Predicts the Location of Traumatic Diffuse Axonal Injury.

Finite element models (FEMs) are used increasingly in the traumatic brain injury (TBI) field to provide an estimation of tissue responses and predict the probability of sustaining TBI after a biomechanical event. However, FEM studies have mainly focused on predicting the absence/presence of TBI rather than estimating the location of injury. In this study, we created a multi-scale FEM of the pig brain with embedded axonal tracts to estimate the sites of acute (≤6 h) traumatic axonal injury (TAI) after rapid head rotation. We examined three finite element (FE)-derived metrics related to the axonal bundle deformation and three FE-derived metrics based on brain tissue deformation for prediction of acute TAI location. Rapid head rotations were performed in pigs, and TAI neuropathological maps were generated and colocalized to the FEM. The distributions of the FEM-derived brain/axonal deformations spatially correlate with the locations of acute TAI. For each of the six metric candidates, we examined a matrix of different injury thresholds (thx) and distance to actual TAI sites (ds) to maximize the average of two optimization criteria. Three axonal deformation-related TAI candidates predicted the sites of acute TAI within 2.5 mm, but no brain tissue metric succeeded. The optimal range of thresholds for maximum axonal strain, maximum axonal strain rate, and maximum product of axonal strain and strain rate were 0.08-0.14, 40-90, and 2.0-7.5 s-1, respectively. The upper bounds of these thresholds resulted in higher true-positive prediction rate. In summary, this study confirmed the hypothesis that the large axonal-bundle deformations occur on/close to the areas that sustained TAI.