Liying Zhang

A Proposed Injury Threshold for Mild Traumatic Brain Injury

Traumatic brain injuries constitute a significant portion of injury resulting from automotive collisions, motorcycle crashes, and sports collisions. Brain injuries not only represent a serious trauma for those involved but also place an enormous burden on society, often exacting a heavy economical, social, and emotional price. Development of intervention strategies to prevent or minimize these injuries requires a complete understanding of injury mechanisms, response and tolerance level. In this study, an attempt is made to delineate actual injury causation and establish a meaningful injury criterion through the use of the actual field accident data. Twenty-four head-to-head field collisions that occurred in professional football games were duplicated using a validated finite element human head model. The injury predictors and injury levels were analyzed based on resulting brain tissue responses and were correlated with the site and occurrence of mild traumatic brain injury (MTBI). Predictions indicated that the shear stress around the brainstem region could be an injury predictor for concussion. Statistical analyses were performed to establish the new brain injury tolerance level.

Comparison of brain responses between frontal and lateral impacts by finite element modeling

This study was conducted to investigate differences in brain response due to frontal and lateral impacts based on a partially validated three-dimensional finite element model with all essential anatomical features of a human head. Identical impact and boundary conditions were used for both the frontal and lateral impact simulations. Intracranial pressure and localized shear stress distributions predicted from these impacts were analyzed. The model predicted higher positive pressures accompanied by a relatively large localized skull deformation at the impact site from a lateral impact when compared to a frontal impact. Lateral impact also induced higher localized shear stress in the core regions of the brain. Preliminary results of the simulation suggest that skull deformation and internal partitions may be responsible for the directional sensitivity of the head in terms of intracranial pressure and shear stress response. In previous experimental studies using subhuman primates, it was found that a lateral impact was more injurious than a frontal impact. In this study, shear stress in the brain predicted by the model was much higher in a lateral impact in comparison with a frontal impact of the same severity. If shear deformation is considered as an injury indicator for diffuse brain injuries, a higher shear stress due to a lateral impact indicate that the head would tend to have a decreased tolerance to shear deformation in lateral impact. More research is needed to further quantify the effect of the skull deformation and dural partitions on brain injury due to impacts from a variety of directions and at different locations.

Concussion in professional football: brain responses by finite element analysis: part 9.

OBJECTIVE:Brain responses from concussive impacts in National Football League football games were simulated by finite element analysis using a detailed anatomic model of the brain and head accelerations from laboratory reconstructions of game impacts. This study compares brain responses with physician determined signs and symptoms of concussion to investigate tissue-level injury mechanisms. METHODS:The Wayne State University Head Injury Model (Version 2001) was used because it has fine anatomic detail of the cranium and brain with more than 300,000 elements. It has 15 different material properties for brain and surrounding tissues. The model includes viscoelastic gray and white brain matter, membranes, ventricles, cranium and facial bones, soft tissues, and slip interface conditions between the brain and dura. The cranium of the finite element model was loaded by translational and rotational accelerations measured in Hybrid III dummies from 28 laboratory reconstructions of NFL impacts involving 22 concussions. Brain responses were determined using a nonlinear, finite element code to simulate the large deformation response of white and gray matter. Strain responses occurring early (during impact) and mid-late (after impact) were compared with the signs and symptoms of concussion. RESULTS:Strain concentration “hot spots” migrate through the brain with time. In 9 of 22 concussions, the early strain “hot spots” occur in the temporal lobe adjacent to the impact and migrate to the far temporal lobe after head acceleration. In all cases, the largest strains occur later in the fornix, midbrain, and corpus callosum. They significantly correlated with removal from play, cognitive and memory problems, and loss of consciousness. Dizziness correlated with early strain in the orbital-frontal cortex and temporal lobe. The strain migration helps explain coup-contrecoup injuries. CONCLUSION:Finite element modeling showed the largest brain deformations occurred after the primary head acceleration. Midbrain strain correlated with memory and cognitive problems and removal from play after concussion. Concussion injuries happen during the rapid displacement and rotation of the cranium, after peak head acceleration and momentum transfer in helmet impacts.

Biomechanics of neurotrauma

Abstract Bioengineering Center, Wayne State University, Detroit, MI, USA This paper reviews the traditional areas of impact biomechanics as they relate to brain injury caused by blunt impact. These areas are injury mechanisms, human response to impact, human tolerance to impact and the use of human surrogates. With the advent of high-speed computers, it is now possible to add computer models to the list of human surrogates that used to be limited to animals and human cadavers. The advantages and shortcomings of current computer models are discussed. One of the computer models was used to predict the pressures and shear stresses developed in the brain and the extent of stretch of the bridging veins in the brains of American football players who sustained severe helmet-to-helmet head impact during the game. It was found that increases in intracranial pressure were more dependent on translational acceleration while the primary determinant for the development of shear stresses in the brain is rotational acceleration. Although the current head injury criterion is based almost entirely on translational acceleration, it is recommended that any new criterion should reflect the contribution of both translational and rotational acceleration. [Neurol Res 2001; 23: 144-156]

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 β-amyloid precursor protein (β-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.

Brain Response to Primary Blast Wave Using Validated Finite Element Models of Human Head and Advanced Combat Helmet

Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen curves for lung injury.

Material Characterization and Computer Model Simulation of Low Density Polyurethane Foam Used in a Rodent Traumatic Brain Injury Model

Computer models of the head can be used to simulate the events associated with traumatic brain injury (TBI) and quantify biomechanical response within the brain. Marmarous impact acceleration rodent model is a widely used experimental model of TBI mirroring axonal pathology in humans. The mechanical properties of the low density polyurethane (PU) foam, an essential piece of energy management used in Marmarous impact device, has not been fully characterized. The foam used in Marmarous device was tested at seven strain rates ranging from quasi-static to dynamic (0.014-42.86 s⁻¹) to quantify the stress-strain relationships in compression. Recovery rate of the foam after cyclic compression was also determined through the periods of recovery up to three weeks. The experimentally determined stress-strain curves were incorporated into a material model in an explicit Finite Element (FE) solver to validate the strain rate dependency of the FE foam model. Compression test results have shown that the foam used in the rodent impact acceleration model is strain rate dependent. The foam has been found to be reusable for multiple impacts. However the stress resistance of used foam is reduced to 70% of the new foam. The FU_CHANG_FOAM material model in an FE solver has been found to be adequate to simulate this rate sensitive foam.

Correlation of mechanical impact responses and biomarker levels: A new model for biomarker evaluation in TBI

A modified Marmarou impact acceleration model was used to help screen biomarkers to assess brain injury severity. Anesthetized male Sprague-Dawley rats were subjected to a closed head injury from 1.25, 1.75 and 2.25 m drop heights. Linear and angular responses of the head were measured in vivo. 24h after impact, cerebrospinal fluid (CSF) and serum were collected. CSF and serum levels of phosphorylated neurofilament heavy (pNF-H), glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), and amyloid beta (Aβ) 1-42 were assessed by enzyme-linked immunosorbent assay (ELISA). Compared to controls, significantly higher CSF and serum pNF-H levels were observed in all impact groups, except between 1.25 m and control in serum. Furthermore, CSF and serum pNF-H levels were significantly different between the impact groups. For GFAP, both CSF and serum levels were significantly higher at 2.25 m compared to 1.75 m, 1.25 m and controls. There was no significant difference in CSF and serum GFAP levels between 1.75 m and 1.25 m, although both groups were significantly higher than control. TBI rats also showed significantly higher levels of IL-6 versus control in both CSF and serum, but no significant difference was observed between each impact group. Levels of Aβ were not significantly different between groups. Pearsons correlation analysis showed pNF-H and GFAP levels in CSF and serum had positive correlation with power (rate of impact energy), followed by average linear acceleration and surface righting (p<0.01), which were good predictors for traumatic axonal injury according to histologic assessment in our previous study, suggesting that they are directly related to the injury mechanism. The model used in this study showed a unique ability in elucidating the relationship between biomarker levels and severity of the mechanical trauma to the brain.

Traumatic Brain Injury by a Closed Head Injury Device Induces Cerebral Blood Flow Changes and Microhemorrhages

Objectives: Traumatic brain injury is a poly-pathology characterized by changes in the cerebral blood flow, inflammation, diffuse axonal, cellular, and vascular injuries. However, studies related to understanding the temporal changes in the cerebral blood flow following traumatic brain injury extending to sub-acute periods are limited. In addition, knowledge related to microhemorrhages, such as their detection, localization, and temporal progression, is important in the evaluation of traumatic brain injury. Materials and Methods: Cerebral blood flow changes and microhemorrhages in male Sprague Dawley rats at 4 h, 24 h, 3 days, and 7 days were assessed following a closed head injury induced by the Marmarou impact acceleration device (2 m height, 450 g brass weight). Cerebral blood flow was measured by arterial spin labeling. Microhemorrhages were assessed by susceptibility-weighted imaging and Prussian blue histology. Results: Traumatic brain injury rats showed reduced regional and global cerebral blood flow at 4 h and 7 days post-injury. Injured rats showed hemorrhagic lesions in the cortex, corpus callosum, hippocampus, and brainstem in susceptibility-weighted imaging. Injured rats also showed Prussian blue reaction products in both the white and gray matter regions up to 7 days after the injury. These lesions were observed in various areas of the cortex, corpus callosum, hippocampus, thalamus, and midbrain. Conclusions: These results suggest that changes in cerebral blood flow and hemorrhagic lesions can persist for sub-acute periods after the initial traumatic insult in an animal model. In addition, microhemorrhages otherwise not seen by susceptibility-weighted imaging are present in diverse regions of the brain. The combination of altered cerebral blood flow and microhemorrhages can potentially be a source of secondary injury changes following traumatic brain injury and may need to be taken into consideration in the long-term care of these cases.

Biomechanical Responses of the Brain in Swine Subject to Free-Field Blasts

Blast-induced traumatic brain injury (bTBI) is a signature wound of modern warfare. The current incomplete understanding of its injury mechanism impedes the development of strategies for effective protection of bTBI. Despite a considerable amount of experimental animal studies focused on the evaluation of brain neurotrauma caused by blast exposure, there is very limited knowledge on the biomechanical responses of the gyrenecephalic brain subjected to primary free-field blast waves imposed in vivo. This study aims to evaluate the external and internal mechanical responses of the brain against different levels of blast loading with Yucatan swine in free field. The incident overpressure (IOP) was generated using 3.6 kg of C4 charge placed at three standoff distances from the swine. Five swine were exposed to a total of 19 blasts. The three average peak IOP pressure levels in this study were 148.8, 278.9, and 409.2 kPa as measured by a pencil probe. The duration of the first positive wave was in the range of 2.1–3 ms. Pressure changes in the brain and head kinematics were recorded with intracranial pressure (ICP) sensors, linear accelerometers, and angular rate sensors. The corresponding average peak ICPs were in the range of 79–143, 210–281, and 311–414 kPa designated as low, medium, and high blast level, respectively. Peak head linear accelerations were in the range of 120–412 g. A positive correlation between IOP and its corresponding biomechanical responses of the brain was also observed. These experimental data can be used to validate computer models of bTBI.