Objective Translational Multi-Domain Early Concussion Assessment

The outcomes of this research project provide opportunities to overcomes some of the challenges in successful translation of animal data into practical applications for humans such as predicting TBI and developing appropriate design criteria for impact sensor technology and protective equipment. In this project. we also develop axonal injury thresholds for repeated TBI for the first time. 
 
 
 Abstract: 
 Traumatic brain injury (TBI). particularly mild-TBI/ concussion. is a major public health issue worldwide which result from head impacts and rapid head rotations usually occurring during high-contact sports. such as football. ice hockey. lacrosse. and soccer. TBI can lead to neurological deficits and functional disabilities. The main driving cause of TBI is recognized to be the rotationally induced tissue deformations and stretch of the axons. Animal models of TBI. in which precise head kinematic loadings can be applied and measured in a controlled laboratory setting and the neuropathology outcomes of TBI can be quantified after sacrifice. play an important role in developing a coupled neuropathology-biomechanical foundation for prediction of likelihood and severity of TBI. However. the important challenge is to design animal studies in a way that represent the human brain biomechanics and brain tissue/axonal deformations in real-world impact incidents in sports. Therefore. in this sub-contract we design appropriate pig study of TBI based on on-field human head kinematic measurements to relate biomechanical loading conditions to underlying brain tissue and axonal deformation (Aim 1) and determine TBI tissue injury thresholds due to single and multiple head impact events in sports using pig model of TBI (Aim 2). In this project. we introduce a novel approach to look at on-filed human head kinematic data and to design translatable animal studies in TBI filed.
 Approach:
 In Aim 1 of this sub-contract. we 1) determine the head impact kinematics corridors and characteristics experienced during soccer games using the head kinematic data that were measured by our collaborators at the Children Hospital of Philadelphia(CHOP) over 2 seasons of suburban high school soccer competitions using headband-mounted impact sensors (SIM-G; Triax Technologies) and confirmed with video analysis [1];2) determine appropriate scaling factors for translating head kinematics parameters between pig and human to get similar brain tissue deformation and axonal stretch in these two species using our previously developed and validated axonal embedded pig brain FEM [2] and a publicly available generalized human head kinematic-based tissue deformation dataset [3];3) determine the appropriate head kinematic loading specifications in different rotational directions that produce axonal stretch and brain tissue deformations in pigs similar to the ones experienced by human in soccer. 
 In Aim 2 of this sub-contract. we 1) use our previously developed and validated axonal embedded pig brain FEM [2-4] to reproduce the new single and multiple pig TBI experiments. that will be performed at Emory University in Year 4 and year 5 of the NIH grant. using the measured head rotational velocity time-histories of these experiments as inputs and compute the axonal and brain tissue deformation during the rapid head rotations in these experiments; 2) use the axonal injury thresholds that we previously determined based on previous single TBI experiments at higher loading conditions [2. 4-5] and explore whether and how closely those thresholds can predict presence/absence and/or distribution/location of injury outcome for the new single and multiple TBI experiments by comparing the FEM and neuropathology results; 3) determine new axonal injury thresholds for repeated TBI capable of predicting outcomes and distributions of axonal damage in multiple and lower loading head rotational conditions in pig TBI experiment with kinematic characteristics that are relevant to real-world human head impacts in soccer.