Evaluation of Tissue-Level Brain Injury Metrics Using Species-Specific Simulations.

Traumatic brain injury (TBI) is a significant public health burden, and the development of advanced countermeasures to mitigate and prevent these injuries during automotive, sports, and military impact events requires an understanding of the intracranial mechanisms related to TBI. In this study, the efficacy of tissue-level injury metrics for predicting TBI was evaluated using finite element reconstructions from a comprehensive, multi-species TBI database. The database consisted of human volunteer tests, laboratory-reconstructed head impacts from sports, in vivo non-human primate (NHP) tests, and in vivo pig tests. Eight tissue-level metrics related to brain tissue strain, axonal strain, and strain-rate were evaluated using survival analysis for predicting mild and severe TBI risk. The correlation between TBI risk and most of the assessed metrics were statistically significant, but when injury data was analyzed by species, the best metric was often inconclusive and limited by the small datasets. When the human and animal datasets were combined, the injury analysis was able to delineate maximum axonal strain as the best predictor of injury for all species and TBI severities, with maximum principal strain as a suitable alternative metric. The current study is the first to provide evidence to support the assumption that brain strain response between human, pig, and NHP result in similar injury outcomes through a multi-species analysis. This assumption is the biomechanical foundation for translating animal brain injury findings to humans. The findings in the study provide fundamental guidelines for developing injury criteria that would contribute towards the innovation of more effective safety countermeasures.

[1]  Taotao Wu,et al.  Investigation of Cross-Species Scaling Methods for Traumatic Brain Injury Using Finite Element Analysis. , 2020, Journal of neurotrauma.

[2]  J. Crisco,et al.  Rotational Head Kinematics in Football Impacts: An Injury Risk Function for Concussion , 2011, Annals of Biomedical Engineering.

[3]  S. Margulies,et al.  Head Rotational Kinematics, Tissue Deformations, and Their Relationships to the Acute Traumatic Axonal Injury , 2020, Journal of biomechanical engineering.

[4]  Matthew R Maltese,et al.  White matter tract-oriented deformation predicts traumatic axonal brain injury and reveals rotational direction-specific vulnerabilities , 2015, Biomechanics and modeling in mechanobiology.

[5]  James R Funk,et al.  A reanalysis of football impact reconstructions for head kinematics and finite element modeling , 2019, Clinical biomechanics.

[6]  M. Symonds,et al.  A brief guide to model selection, multimodel inference and model averaging in behavioural ecology using Akaike’s information criterion , 2010, Behavioral Ecology and Sociobiology.

[7]  Matthew B. Panzer,et al.  Development of a Finite Element Model for Blast Brain Injury and the Effects of CSF Cavitation , 2012, Annals of Biomedical Engineering.

[8]  James H. McElhaney,et al.  Side Impact Tolerance to Blunt Trauma , 1973 .

[9]  Stefan M. Duma,et al.  Brain Injury Prediction: Assessing the Combined Probability of Concussion Using Linear and Rotational Head Acceleration , 2013, Annals of Biomedical Engineering.

[10]  S. Margulies,et al.  Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using Cyclosporin A as a Case Study , 2015, Brain pathology.

[11]  Matthew B. Panzer,et al.  State-of-the-Art Modeling and Simulation of the Brain’s Response to Mechanical Loads , 2019, Annals of Biomedical Engineering.

[12]  Guy S. Nusholtz,et al.  Critical Limitations on Significant Factors in Head Injury Research , 1986 .

[13]  S. Margulies,et al.  An analytical model of traumatic diffuse brain injury. , 1989, Journal of biomechanical engineering.

[14]  Thomas A. Gennarelli,et al.  Directional Dependence of Axonal Brain Injury due to Centroidal and Non-Centroidal Acceleration , 1987 .

[15]  J. Sebastian Giudice,et al.  Explicit Modeling of White Matter Axonal Fiber Tracts in a Finite Element Brain Model , 2019, Annals of Biomedical Engineering.

[16]  D. Viano,et al.  Concussion in Professional Football: Reconstruction of Game Impacts and Injuries , 2003, Neurosurgery.

[17]  R. Ogden,et al.  Hyperelastic modelling of arterial layers with distributed collagen fibre orientations , 2006, Journal of The Royal Society Interface.

[18]  Matthew B. Panzer,et al.  Development of a Second-Order System for Rapid Estimation of Maximum Brain Strain , 2018, Annals of Biomedical Engineering.

[19]  Matthew B. Panzer,et al.  Scaling in neurotrauma: How do we apply animal experiments to people? , 2014, Experimental Neurology.

[20]  Matthew B. Panzer,et al.  Development of a Metric for Predicting Brain Strain Responses Using Head Kinematics , 2018, Annals of Biomedical Engineering.

[21]  Li Li,et al.  Intraventricular hemorrhage on initial computed tomography as marker of diffuse axonal injury after traumatic brain injury. , 2015, Journal of neurotrauma.

[22]  B. Morrison,et al.  Mechanical Stretch of High Magnitude Provokes Axonal Injury, Elongation of Paranodal Junctions, and Signaling Alterations in Oligodendrocytes , 2018, Molecular Neurobiology.

[23]  D. Meaney,et al.  Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury. , 2000, Journal of biomechanical engineering.

[24]  Matthew B. Panzer,et al.  Brain tissue strains vary with head impact location: A possible explanation for increased concussion risk in struck versus striking football players , 2019, Clinical biomechanics.

[25]  Peter J Hellyer,et al.  Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology , 2017, Brain : a journal of neurology.

[26]  J. Forman,et al.  Biomechanics of the Human Brain During Dynamic Rotation of the Head. , 2020, Journal of neurotrauma.

[27]  M. Gilchrist,et al.  Mechanical characterization of brain tissue in tension at dynamic strain rates. , 2020, Journal of the mechanical behavior of biomedical materials.

[28]  S. Margulies,et al.  Physiological and pathological responses to head rotations in toddler piglets. , 2010, Journal of neurotrauma.

[29]  L. Sundstrom,et al.  Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate. , 2006, Journal of biomechanics.

[30]  B. PanzerMatthew,et al.  Evaluation of Head and Brain Injury Risk Functions Using Sub-Injurious Human Volunteer Data. , 2017 .

[31]  J. Adams,et al.  Diffuse axonal injury and traumatic coma in the primate , 1982, Annals of neurology.

[32]  Timothy L McMurry,et al.  Statistical Considerations in the Development of Injury Risk Functions , 2015, Traffic injury prevention.

[33]  Rodney X. Sturdivant,et al.  Applied Logistic Regression: Hosmer/Applied Logistic Regression , 2005 .

[34]  Taotao Wu,et al.  Embedded axonal fiber tracts improve finite element model predictions of traumatic brain injury , 2019, Biomechanics and modeling in mechanobiology.

[35]  Rémy Willinger,et al.  Brain injury tolerance limit based on computation of axonal strain. , 2016, Accident; analysis and prevention.

[36]  Susan Margulies,et al.  Multi-scale white matter tract embedded brain finite element mode predicts the location of traumatic diffuse axonal injury. , 2020, Journal of neurotrauma.

[37]  S. Herculano‐Houzel,et al.  You Do Not Mess with the Glia , 2018, Neuroglia.

[38]  D. Posada,et al.  Model selection and model averaging in phylogenetics: advantages of akaike information criterion and bayesian approaches over likelihood ratio tests. , 2004, Systematic biology.