Haojie Mao

A comprehensive experimental study on material properties of human brain tissue

A comprehensive study on the biomechanical response of human brain tissue is necessary to investigate traumatic brain injury mechanisms. Published brain material property studies have been mostly performed under a specific type of loading, which is insufficient to develop accurate brain tissue constitutive equations. In addition, inconsistent or contradictory data in the literature made it impossible for computational model developers to create a single brain material model that can fit most, if not all, experimental results. In the current study, a total of 240 brain tissue specimens were tested under tension (n=72), compression (n=72), and shear (n=96) loading modes at varying strain rates. Gray-white matter difference, regional difference, and directional difference within white matter were also investigated. Stress-strain relationships of human brain tissue were obtained up to 50% of engineering strain. Strain rate dependency was observed under all three loading modes. White matter was stiffer than gray matter in compression and shear. Corona radiata was found to be stiffer than cortex, thalamus, and corpus callosum in tension and compression. Directional dependency of white matter was observed under shear loading.

Rate of Neurodegeneration in the Mouse Controlled Cortical Impact Model Is Influenced by Impactor Tip Shape: Implications for Mechanistic and Therapeutic Studies

Controlled cortical impact (CCI), one of the most common models of traumatic brain injury, is being increasingly used with mice for exploration of cell injury mechanisms and pre-clinical evaluation of therapeutic strategies. Although CCI brain injury was originally effected using an impactor with a rounded tip, the majority of studies with mouse CCI use a flat or beveled tip. Recent finite element modeling analyses demonstrate that tip geometry is a significant determinant of predicted cortical tissue strains in rat CCI, and that cell death is proportional to predicted tissue strains. In the current study, a three-dimensional finite element model of a C57BL/6J mouse brain predicted higher maximum principal strains during a simulated 1.0-mm, 3.5-m/s CCI injury with a flat tip when compared to a rounded tip. Consistent with this prediction, experimental CCI with a flat-tip impactor resulted in greater acute cortical hemorrhage and neuron loss in adult male C57BL/6J mice. The amount of neocortical tissue damage was equivalent for the two tip geometries at 9 days following injury, but the rate of neocortical neurodegeneration was markedly slower following CCI with a rounded-tip impactor, with damage reaching a plateau after 24?h as opposed to after 4?h for the flat tip. The flat-tip impactor was associated in general with more regional hippocampal neurodegeneration, especially at early time points such as 4?h. Impactor tip geometry did not have a notable effect on blood?brain barrier breakdown, traumatic axonal injury, or motor and cognitive dysfunction. Execution of CCI injury with a rounded-tip impactor is posited to provide a substantially enhanced temporal window for the study of cellular injury mechanisms and therapeutic intervention while maintaining critical aspects of the pathophysiological response to contusion brain injury.

Computational neurotrauma—design, simulation, and analysis of controlled cortical impact model

The controlled cortical impact (CCI) model is widely used in many laboratories to study traumatic brain injury (TBI). Although external impact parameters during CCI tests could be clearly defined, little is known about the internal tissue-level mechanical responses of the rat brain. Furthermore, the external impact parameters tend to vary considerably among different labs making the comparison of research findings difficult if not impossible. In this study, a design of computer experiments was performed with typical external impact parameters commonly found in the literature. An anatomically detailed finite element (FE) rat brain model was used to simulate the CCI experiments to correlate external mechanical parameters (impact depth, impact velocity, impactor shape, impactor size, and craniotomy pattern) with rat brain internal responses, as predicted by the FE model. Systematic analysis of the results revealed that impact depth was the leading factor affecting the predicted brain internal responses. Interestingly, impactor shape ranked as the second most important factor, surpassing impactor diameter and velocity which were commonly reported in the literature as indicators of injury severity along with impact depth. The differences in whole brain response due to a unilateral or a bilateral craniotomy were small, but those of regional intracranial tissue stretches were large. The interaction effects of any two external parameters were not significant. This study demonstrates the potential of using numerical FE modeling to engineer better experimental TBI models in the future.

Development and Validation of a 10-Year-Old Child Ligamentous Cervical Spine Finite Element Model

Although a number of finite element (FE) adult cervical spine models have been developed to understand the injury mechanisms of the neck in automotive related crash scenarios, there have been fewer efforts to develop a child neck model. In this study, a 10-year-old ligamentous cervical spine FE model was developed for application in the improvement of pediatric safety related to motor vehicle crashes. The model geometry was obtained from medical scans and meshed using a multi-block approach. Appropriate properties based on review of literature in conjunction with scaling were assigned to different parts of the model. Child tensile force–deformation data in three segments, Occipital-C2 (C0–C2), C4–C5 and C6–C7, were used to validate the cervical spine model and predict failure forces and displacements. Design of computer experiments was performed to determine failure properties for intervertebral discs and ligaments needed to set up the FE model. The model-predicted ultimate displacements and forces were within the experimental range. The cervical spine FE model was validated in flexion and extension against the child experimental data in three segments, C0–C2, C4–C5 and C6–C7. Other model predictions were found to be consistent with the experimental responses scaled from adult data. The whole cervical spine model was also validated in tension, flexion and extension against the child experimental data. This study provided methods for developing a child ligamentous cervical spine FE model and to predict soft tissue failures in tension.

Modeling of the Brain for Injury Prevention

From an ethical point of view, it is extremely difficult to propose a well-controlled human subject study aimed at understanding brain injury mechanisms and establishing the associated tolerance values. For this reason, many numerical models of the human and animal head or brain have been developed over the past several decades in an attempt to obtain in-depth insights into brain injury biomechanics, minimizing the need for human subject research. This chapter highlights and contrasts the essence of human and animal head numerical models developed for studying blunt impact and blast-induced brain injuries. Even with the vast amount of literature produced by these investigations and studies, the precise mechanisms of brain injury have not yet been fully established to date. Through this review, it is clear that a lot of information can be garnered by numerical brain modeling but few efforts have been devoted so far in using these numerical models to provide guidelines in the discovery of brain injury mechanisms. Based on the brain models reported in the current literature, there are some inherent deficiencies. However, with further revisions and improvements to the currently available models, as opposed to developing new models from scratch, these issues can be overcome, and the state of the art can be advanced. More research effort into brain injury mechanisms, especially under in vivo conditions, is needed for computational model improvements so that the injury mechanisms can be thoroughly understood and effective countermeasures for protecting human from traumatic brain injury can be developed.

A Modified Controlled Cortical Impact Technique to Model Mild Traumatic Brain Injury Mechanics in Mice

For the past 25 years, controlled cortical impact (CCI) has been a useful tool in traumatic brain injury (TBI) research, creating injury patterns that includes primary contusion, neuronal loss, and traumatic axonal damage. However, when CCI was first developed, very little was known on the underlying biomechanics of mild TBI. This paper uses information generated from recent computational models of mild TBI in humans to alter CCI and better reflect the biomechanical conditions of mild TBI. Using a finite element model of CCI in the mouse, we adjusted three primary features of CCI: the speed of the impact to achieve strain rates within the range associated with mild TBI, the shape, and material of the impounder to minimize strain concentrations in the brain, and the impact depth to control the peak deformation that occurred in the cortex and hippocampus. For these modified cortical impact conditions, we observed peak strains and strain rates throughout the brain were significantly reduced and consistent with estimated strains and strain rates observed in human mild TBI. We saw breakdown of the blood–brain barrier but no primary hemorrhage. Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury. Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively. Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment.

Biomechanical responses of a pig head under blast loading: a computational simulation

A series of computational studies were performed to investigate the biomechanical responses of the pig head under a specific shock tube environment. A finite element model of the head of a 50-kg Yorkshire pig was developed with sufficient details, based on the Lagrangian formulation, and a shock tube model was developed using the multimaterial arbitrary Lagrangian-Eulerian (MMALE) approach. These two models were integrated and a fluid/solid coupling algorithm was used to simulate the interaction of the shock wave with the pigs head. The finite element model-predicted incident and intracranial pressure traces were in reasonable agreement with those obtained experimentally. Using the verified numerical model of the shock tube and pig head, further investigations were carried out to study the spatial and temporal distributions of pressure, shear stress, and principal strain within the head. Pressure enhancement was found in the skull, which is believed to be caused by shock wave reflection at the interface of the materials with distinct wave impedances. Brain tissue has a shock attenuation effect and larger pressures were observed in the frontal and occipital regions, suggesting a greater possibility of coup and contrecoup contusion. Shear stresses in the brain and deflection in the skull remained at a low level. Higher principal strains were observed in the brain near the foramen magnum, suggesting that there is a greater chance of cellular or vascular injuries in the brainstem region.

Why is CA3 more vulnerable than CA1 in experimental models of controlled cortical impact-induced brain injury?

One interesting finding of controlled cortical impact (CCI) experiments is that the CA3 region of the hippocampus, which is positioned further from the impact than the CA1 region, is reported as being more injured. The current literature has suggested a positive correlation between brain tissue stretch and neuronal cell loss. However, it is counterintuitive to assume that CA3 is stretched more during CCI injury. Recent mechanical studies of the brain have reported on a level of spatial heterogeneity not previously appreciated-the finding that CA1 was significantly stiffer than all other regions tested and that CA3 was one of the most compliant. We hypothesized that mechanical heterogeneity of anatomical structures could underlie the proposed heterogeneous mechanical response and hence the pattern of cell death. As such, we developed a three-dimensional finite element (FE) rat brain model representing detailed hippocampal structures and simulated various CCI experiments. Four groups of material properties based on recent experiments were tested. In group 1, hyperelastic material properties were assigned to various hippocampal structures, with CA3 more compliant than CA1. In group 2, linear viscoelastic material properties were assigned to hippocampal structures, with CA3 more compliant than CA1. In group 3, the hippocampus was represented by homogenous linear viscoelastic material properties. In group 4, a homogeneous nonlinear hippocampus was adopted. Simulation results demonstrated that for CCI with a 5-mm diameter, flat shape impactor, CA3 experienced increased tensile strains over a larger area and to a greater magnitude than did CA1 for group 1, which best explained why CA3 is more sensitive to CCI injury. However, for groups 2-4, the total volume with high strain (>30%) in CA3 was smaller than that in CA1. The FE rat brain model, with detailed hippocampal structures presented here, will help to engineer desired experimental neurotrauma models by virtually characterizing brain biomechanics before testing.

Development of a 10-year-old paediatric thorax finite element model validated against cardiopulmonary resuscitation data

Thoracic injury in the paediatric population is a relatively common cause of severe injury and has an accompanying high mortality rate. However, no anatomically accurate, complex paediatric chest finite element (FE) component model is available for a 10-year old in the published literature. In this study, a 10-year-old thorax FE model was developed based on internal and external geometries segmented from medical images. The model was then validated against published data measured during cardiopulmonary resuscitation performed on paediatric subjects.

Development of high-quality hexahedral human brain meshes using feature-based multi-block approach

The finite element (FE) method is a powerful tool to study brain injury that remains to be a critical health concern. Subject/patient-specific FE brain models have the potential to accurately predict a specific subject/patients brain responses during computer-assisted surgery or to design subject-specific helmets to prevent brain injury. Unfortunately, efforts required in the development of high-quality hexahedral FE meshes for brain, which consists of complex intracranial surfaces and varying internal structures, are daunting. Using multi-block techniques, an efficient meshing process to develop all-hexahedral FE brain models for an adult and a paediatric brain (3-year old) was demonstrated in this study. Furthermore, the mesh densities could be adjusted at ease using block techniques. Such an advantage can facilitate a mesh convergence study and allows more freedom for choosing an appropriate brain mesh density by balancing available computation power and prediction accuracy. The multi-block meshing approach is recommended to efficiently develop 3D all-hexahedral high-quality models in biomedical community to enhance the acceptance and application of numerical simulations.