Abstract
Axonal injury represents a critical target area for the prevention and treatment of traumatic brain and spinal cord injuries. Finite element (FE) models of the head and/or brain are often used to predict brain injury caused by external mechanical loadings, such as explosive waves and direct impact. The accuracy of these numerical models depends on correctly determining the material properties and on the precise depiction of the tissues’ microstructure (microscopic level). Moreover, since the axonal microstructure for specific regions of the brain white matter is locally oriented, the stress, and strain fields are highly anisotropic and axon orientation dependent. Additionally, mechanical strain has been identified as the proximal cause of axonal injury, which further demonstrates the importance of this multi-scale relationship. In this study, our previously developed FE and kinematic axonal models are coupled and applied to a pseudo 3-dimensional representative volume element of central nervous system white matter to investigate the multi-scale mechanical behavior. An inverse FE procedure was developed to identify material parameters of spinal cord white matter by combining the results of uniaxial testing with FE modeling. A satisfactory balance between simulation and experiment was achieved via optimization by minimizing the squared error between the simulated and experimental force-stretch curve. The combination of experimental testing and FE analysis provides a useful analysis tool for soft biological tissues in general, and specifically enables evaluations of the axonal response to tissue-level loading and subsequent predictions of axonal damage.
Highlights
An increase in the incidence and improvements in the diagnosis of traumatic brain injury (TBI) have increased awareness of the public about TBI’s serious health effects
A pseudo-3D representative volume element (RVE) for the central nervous system (CNS) white matter is composed of many undulated axons that are embedded in the extracellular matrix (ECM)
A novel pseudo-3D RVE with axon kinematics was developed to capture the kinematics of axons and the stress-stretch behavior of CNS white matter
Summary
An increase in the incidence and improvements in the diagnosis of traumatic brain injury (TBI) have increased awareness of the public about TBI’s serious health effects. Axonal injury, which is considered to be a major contributor to cognitive dysfunction following TBI, represents a critical focal area for TBI and spinal cord injury (SCI) prevention and treatment. FE models (FEM) of the head and/or brain are often used to predict brain injury caused by mechanical loading. Many attempts have been made to understand the injury mechanism and to define the mechanical parameters that govern axonal injury. Mechanical strain has been identified as the proximal cause of axonal injury (Wright and Ramesh, 2012), while secondary ischemic and excitotoxic insults associated with the primary trauma potentially exacerbate the structural and functional damage. Efforts to simulate the deformation, stress, and strain fields of brain tissues using computational models have primarily treated brain tissues as homogeneous materials, albeit with potential differences in properties between gray and white matter. Stress and strain fields were obtained in an average sense, which can be interpreted as macroscopic behavior (Kleiven, 2006; Ho and Kleiven, 2007; Cloots et al, 2008; Mao et al, 2010)
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