Abstract
Mechanical aspects play an important role in brain development, function, and disease. Therefore, continuum-mechanics-based computational models are a valuable tool to advance our understanding of mechanics-related physiological and pathological processes in the brain. Currently, mainly phenomenological material models are used to predict the behavior of brain tissue numerically. The model parameters often lack physical interpretation and only provide adequate estimates for brain regions which have a similar microstructure and age as those used for calibration. These issues can be overcome by establishing advanced constitutive models that are microstructurally motivated and account for regional heterogeneities through microstructural parameters.In this work, we perform simultaneous compressive mechanical loadings and microstructural analyses of porcine brain tissue to identify the microstructural mechanisms that underlie the macroscopic nonlinear and time-dependent mechanical response. Based on experimental insights into the link between macroscopic mechanics and cellular rearrangements, we propose a microstructure-informed finite viscoelastic constitutive model for brain tissue. We determine a relaxation time constant from cellular displacement curves and introduce hyperelastic model parameters as linear functions of the cell density, as determined through histological staining of the tested samples. The model is calibrated using a combination of cyclic loadings and stress relaxation experiments in compression. The presented considerations constitute an important step towards microstructure-based viscoelastic constitutive models for brain tissue, which may eventually allow us to capture regional material heterogeneities and predict how microstructural changes during development, aging, and disease affect macroscopic tissue mechanics.
Highlights
Mechanical forces and signals have recently been identified as an important influencing factor for brain development, injury, and disease [22, 29]
In an initial test series, we aimed to define the limit of brain viscoelasticity, i.e. the macroscopic loading that still allows for the full recovery of the mechanical response of brain tissue
We have provided important insights into the microstructural origin of brain viscoelasticity through the simultaneous analysis of the macroscopic mechanical response and microstructural rearrangements of porcine brain tissue samples
Summary
Mechanical forces and signals have recently been identified as an important influencing factor for brain development, injury, and disease [22, 29]. An additional advantage of microstructure-informed constitutive models is that they enable us to predict how (local) changes in the tissue’s microstructure that may occur during development and aging or due to injury and disease translate into changes in macroscopic mechanical properties This is highly relevant in the context of certain diseases, where microstructural changes are known but the link to the corresponding tissue mechanics remains unclear [6, 16]. Recent efforts towards micromechanical modeling of brain tissue have proposed to include the individual contributions of axons and extracellular matrix in white matter tissue [25, 42] or the brain stem [2, 26] through representative volume elements accounting for the distribution and orientation of nerve fiber bundles from magnetic resonance and diffusion tensor imaging data It remains controversial whether axons majorly contribute to the mechanical response of brain tissue [12, 15, 20, 51] and such models would only be valid for certain white matter areas.
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