Fifty Shades of Brain: A Review on the Mechanical Testing and Modeling of Brain Tissue

Abstract

Brain tissue is not only one of the most important but also the most complex and compliant tissue in the human body. While long underestimated, increasing evidence confirms that mechanics plays a critical role in modulating brain function and dysfunction. Computational simulations-based on the field equations of nonlinear continuum mechanics-can provide important insights into the underlying mechanisms of brain injury and disease that go beyond the possibilities of traditional diagnostic tools. Realistic numerical predictions, however, require mechanical models that are capable of capturing the complex and unique characteristics of this ultrasoft, heterogeneous, and active tissue. In recent years, contradictory experimental results have caused confusion and hindered rapid progress. In this review, we carefully assess the challenges associated with brain tissue testing and modeling, and work out the most important characteristics of brain tissue behavior on different length and time scales. Depending on the application of interest, we propose appropriate mechanical modeling approaches that are as complex as necessary but as simple as possible. This comprehensive review will, on the one hand, stimulate the design of new experiments and, on the other hand, guide the selection of appropriate constitutive models for specific applications. Mechanical models that capture the complex behavior of nervous tissues and are accurately calibrated with reliable and comprehensive experimental data are key to performing reliable predictive simulations. Ultimately, mathematical modeling and computational simulations of the brain are useful for both biomedical and clinical communities, and cover a wide range of applications ranging from predicting disease progression and estimating injury risk to planning surgical procedures.

Mechanical Characterization and Modeling of the Porcine Cerebral Meninges

“…There is no global agreement on the effect of prolonged storage of brain tissue on mechanical properties, with some authors concluding there is minimal effect up until 5 days post-mortem (Budday et al, 2015 ), while others conclude that as short as 6 h of storage can affect the properties (Garo et al, 2007 ). As concluded by Budday et al ( 2019 ) in their review paper of brain tissue, we have considered that, provided the tissue is kept sufficiently hydrated, the degeneration process of post-mortem tissues is negligible. Similarly, it has been previously reported that increasing the temperature from ambient conditions to physiological conditions (37°C) significantly reduces the stiffness of brain tissue (Pogoda et al, 2014 ).…”

Mechanosensitivity of Human Oligodendrocytes

“…We adapted the directed differentiation of human oligodendrocytes from hiPSCs that we previously developed (Douvaras et al, 2014;Douvaras and Fossati, 2015) to a well-established system of polyacrylamide (PAAm) hydrogels (Tse and Engler, 2010;Pelham and Wang, 1997;Moshayedi et al, 2010;Jagielska et al, 2012) functionalized to facilitate cell adhesion to their surface ( Figure 1A). The hydrogels mimic a range of stiffness described by Young's elastic modulus E (of magnitude 0.1-70 kPa) that approximates and exceeds the stiffness of the human CNS environment (Murphy et al, 2016;Budday et al, 2017Budday et al, , 2019McIlvain et al, 2018;Urbanski et al, 2019; Figures 1B,C). In other words, these hydrogels span the range of physiological and pathological CNS stiffness.…”

An anatomically accurate and personalizable head injury model: Significance of brain and white matter tract morphological variability on strain

“…Some experimental studies suggest that brain tissue is mechanically isotropic, e.g., Budday et al (2017), while others suggest brain tissue show significant directional trends, e.g., Prange and Margulies (2002), Feng et al (2017). More discussion on the controversies can be found in a review study by Budday et al (2019). Nevertheless, both isotropic and anisotropic models are being used in head models for studying TBIs; see review studies (Giudice et al 2019;Madhukar and Ostoja-Starzewski 2019).…”