Development and Validation of a New Anisotropic Visco-Hyperelastic Human Head Finite Element Model Capable of Predicting Multiple Brain Injuries.

This paper reports on the latest refinement of the Finite Element Global Human Body Models Consortium 50th percentile (GHBMC M50) adult male head model by the development and incorporation of a new material model into the white matter tissue of the brain. The white matter is represented by an anisotropic visco-hyperelastic material model capable of simulating direction-dependent response of the brain tissue to further improve the bio-fidelity and injury predictive capability of the model. The parameters representing the material were optimized by comparing model responses to seven experimentally reported strain responses of brains of postmortem human subjects (PMHS) subjected to head impact. The head model was subjected to rigorous validation against experimental data on force-deflection responses in the skull and face, intracranial pressure, and brain strain responses from over 34 PMHS head impact experiments. Crash-induced injury indices (CIIs) for facial bone fracture, skull fracture, cerebral contusion, acute subdural hematomas (ASDHs), and diffuse brain injury were developed by reconstructing 32 PMHS and real-world injury cases with the model. Model predicted maximum principal strain (MPS) and stress were determined as fracture CIIs for compact bone and spongy bones, respectively, in the skull and face. Brain responses in terms of MPS, MPS rates, and pressure distribution in injury producing experimental impacts were determined using the model and analyzed with logistic regression and survival analysis to develop CIIs for brain contusions, diffuse brain injuries, and ASDH. The statistical models using logistic regression and survival analysis showed high accuracy with area under the receiver operating curve greater than 0.8. Because of lack of sufficient moderate diffuse brain injury data, a statistical model was not created, but all indications are that the MPS rate is an essential brain response that discriminates between moderate and severe brain injuries. The authors stated that the current GHBMC M50 v.6.0 is an advanced tool for injury prediction and mitigation of injuries in automotive crashes, sports, recreational, and military environments.

Investigate the Variations of the Head and Brain Response in a Rodent Head Impact Acceleration Model by Finite Element Modeling.

Diffuse axonal injury (DAI) is a severe form of traumatic brain injury and often induced by blunt trauma. The closed head impact acceleration (IA) model is the most widely used rodent DAI model. However, this model results in large variations of injury severity. Recently, the impact device/system was modified to improve the consistency of the impact energy, but variations of the head kinematics and subsequent brain injuries were still observed. This study was aimed to utilize a Finite Element (FE) model of a rat head/body and simulation to investigate the potential biomechanical factors influencing the impact energy transfer to the head. A detailed FE rat head model containing detailed skull and brain anatomy was developed based on the MRI, microCT and atlas data. The model consists of over 722,000 elements, of which 310,000 are in the brain. The white matter structures consisting of highly aligned axonal fibers were simulated with transversely isotropic material. The rat body was modeled to provide a realistic boundary at the spine-medulla junction. Rodent experiments including dynamic cortical deformation, brain-skull displacement, and IA kinematics were simulated to validate the FE model. The model was then applied to simulate the rat IA experiments. Parametric studies were conducted to investigate the effect of the helmet inclination angles (0°-5°) and skull stiffness (varied 20%) on the resulting head kinematics and maximum principal strain in the brain. The inclination angle of the helmet at 5° could vary head linear acceleration by 8-31%. The change in head rotational velocity was inversely related to the change in linear acceleration. Varying skull stiffness resulted in changes in head linear acceleration by 3% but with no effect on rotational velocity. The brain strain in the corpus callosum was only affected by head rotation while the strain in the brainstem was influenced by the combined head kinematics, local skull deformation, and head-neck position. Validated FE models of rat impact head injury can assist in exploring various biomechanical factors influencing the head impact response and internal brain response. Identification of these variables may help explain the variability of injury severity observed among experiments and across different labs.

Porcine growth plate experimental study and estimation of human pediatric growth plate properties.

Growth plate (GP) is a type of tissue widely found in child's immature skeleton. It may have significant influence on the overall injury pattern since it has distinguishing mechanical properties compared to the surrounding bony tissue. For more accurate material modeling and advanced pediatric human body modeling, it is imperative to investigate the material property of GPs in different loading conditions. In this study, a series of tensile and shearing experiments on porcine bone-GP-bone units were carried out. Total 113 specimens of bone-GP-bone unit from the femoral head, distal femur, and proximal tibia of four 20-weeks-old piglets were tested, under different strain rates (average 0.0053 to 1.907 s-1 for tensile tests, and 0.0085 to 3.037 s-1 for shearing tests). Randomized block ANOVA was conducted to determine the effects of anatomic region and strain rate on the material properties of GPs. It was found that, strain rate is a significant factor for modulus and ultimate stress for both tensile and shearing tests; the ultimate strains are not sensitive to the input factors in both tensile and shearing tests; the GPs at knee region could be grouped due to similar properties, but statistically different from the femoral head GP. Additionally, the tensile test data from the experimental study were comparing to the limited data obtained from tests on human subjects reported in the literature. An optimal conversion factor was derived to correlate the material properties of 20-week-old piglet GPs and 10 YO child GPs. As a result, the estimated material properties of 10 YO child GPs from different regions in different loading conditions became available given the conversion law stays legitimate. These estimated material properties for 10 YO child GPs were reported in the form of tensile and shearing stress-strain curves and could be subsequently utilized for human GP tissue material modeling and child injury mechanism studies.

Mechanoporation is a potential indicator of tissue strain and subsequent degeneration following experimental traumatic brain injury.

BACKGROUND: An increases in plasma membrane permeability is part of the acute pathology of traumatic brain injury and may be a function of excessive membrane force. This membrane damage, or mechanoporation, allows non-specific flux of ions and other molecules across the plasma membrane, and may ultimately lead to cell death. The relationships among tissue stress and strain, membrane permeability, and subsequent cell degeneration, however, are not fully understood. METHODS: Fluorescent molecules of different sizes were introduced to the cerebrospinal fluid space prior to injury and animals were sacrificed at either 10 min or 24 h after injury. We compared the spatial distribution of plasma membrane damage following controlled cortical impact in the rat to the stress and strain tissue patterns in a 3-D finite element simulation of the injury parameters. FINDINGS: Permeable cells were located primarily in the ipsilateral cortex and hippocampus of injured rats at 10 min post-injury; however by 24 h there was also a significant increase in the number of permeable cells. Analysis of colocalization of permeability marker uptake and Fluorojade staining revealed a subset of permeable cells with signs of degeneration at 24 h, but plasma membrane damage was evident in the vast majority of degenerating cells. The regional and subregional distribution patterns of the maximum principal strain and shear stress estimated by the finite element model were comparable to the cell membrane damage profiles following a compressive impact. INTERPRETATION: These results indicate that acute membrane permeability is prominent following traumatic brain injury in areas that experience high shear or tensile stress and strain due to differential mechanical properties of the cell and tissue organization, and that this mechanoporation may play a role in the initiation of secondary injury, contributing to cell death.

Impaired axoplasmic transport is the dominant injury induced by an impact acceleration injury device: an analysis of traumatic axonal injury in pyramidal tract and corpus callosum of rats.

Traumatic axonal injury (TAI) involves neurofilament compaction (NFC) and impaired axoplasmic transport (IAT) in distinct populations of axons. Previous quantification studies of TAI focused on limited areas of pyramidal tract (Py) but not its entire length. Quantification of TAI in corpus callosum (CC) and its comparison to that in Py is also lacking. This study assessed and compared the extent of TAI in the entire Py and CC of rats following TBI. TBI was induced by a modified Marmarou impact acceleration device in 31 adult male Sprague Dawley rats by dropping a 450 gram impactor from either 1.25 m or 2.25 m. Twenty-four hours after TBI, TAI was assessed by beta amyloid precursor protein (ß-APP-IAT) and RMO14 (NFC) immunocytochemistry. TAI density (ß-APP and RMO14 axonal swellings, retraction balls and axonal profiles) was counted from panoramic images of CC and Py. Significantly high TAI was observed in 2.25 m impacted rats. ß-APP immunoreactive axons were significantly higher in number than RMO14 immunoreactive axons in both the structures. TAI density in Py was significantly higher than in CC. Based on our parallel biomechanical studies, it is inferred that TAI in CC may be related to compressive strains and that in Py may be related to tensile strains. Overall, IAT appears to be the dominant injury type induced by this model and injury in Py predominates that in CC.

Quantitative relationship between axonal injury and mechanical response in a rodent head impact acceleration model.

A modified Marmarou impact acceleration model was developed to study the mechanical responses induced by this model and their correlation to traumatic axonal injury (TAI). Traumatic brain injury (TBI) was induced in 31 anesthetized male Sprague-Dawley rats (392±13 g) by a custom-made 450-g impactor from heights of 1.25 m or 2.25 m. An accelerometer and angular rate sensor measured the linear and angular responses of the head, while the impact event was captured by a high-speed video camera. TAI distribution along the rostro-caudal direction, as well as across the left and right hemispheres, was determined using ß-amyloid precursor protein (ß-APP) immunocytochemistry, and detailed TAI injury maps were constructed for the entire corpus callosum. Peak linear acceleration 1.25 m and 2.25 m impacts were 666±165 g and 907±501 g, respectively. Peak angular velocities were 95±24 rad/sec and 124±48 rad/sec, respectively. Compared to the 2.25-m group, the observed TAI counts in the 1.25-m impact group were significantly lower. Average linear acceleration, peak angular velocity, average angular acceleration, and surface righting time were also significantly different between the two groups. A positive correlation was observed between normalized total TAI counts and average linear acceleration (R(2)=0.612, p<0.05), and time to surface right (R(2)=0.545, p<0.05). Our study suggested that a 2.25-m drop in the Marmarou model may not always result in a severe injury, and TAI level is related to the linear and angular acceleration response of the rat head during impact, not necessarily the drop height.

Injury predictors for traumatic axonal injury in a rodent head impact acceleration model.

A modified Marmarou impact acceleration injury model was developed to study the kinematics of the rat head to quantify traumatic axonal injury (TAI) in the corpus callosum (CC) and brainstem pyramidal tract (Py), to determine injury predictors and to establish injury thresholds for severe TAI. Thirty-one anesthetized male Sprague-Dawley rats (392±13 grams) were impacted using a modified impact acceleration injury device from 2.25 m and 1.25 m heights. Beta-amyloid precursor protein (ß-APP) immunocytochemistry was used to assess and quantify axonal changes in CC and Py. Over 600 injury maps in CC and Py were constructed in the 31 impacted rats. TAI distribution along the rostro-caudal direction in CC and Py was determined. Linear and angular responses of the rat head were monitored and measured in vivo with an attached accelerometer and angular rate sensor, and were correlated to TAI data. Logistic regression analysis suggested that the occurrence of severe TAI in CC was best predicted by average linear acceleration, followed by power and time to surface righting. The combination of average linear acceleration and time to surface righting showed an improved predictive result. In Py, severe TAI was best predicted by time to surface righting, followed by peak and average angular velocity. When both CC and Py were combined, power was the best predictor, and the combined average linear acceleration and average angular velocity was also found to have good injury predictive ability. Receiver operator characteristic curves were used to assess the predictive power of individual and paired injury predictors. TAI tolerance curves were also proposed in this study.