Research paper
Mechanical properties of brain tissue by indentation: Interregional variation

https://doi.org/10.1016/j.jmbbm.2009.09.001Get rights and content

Abstract

Although many studies on the mechanical properties of brain tissue exist, some controversy concerning the possible differences in mechanical properties of white and gray matter tissues remains. Indentation experiments are conducted on white and gray matter tissues of various regions of the cerebrum and on tissue from the thalamus and the midbrain to study interregional differences. An advantage of indentation, when compared to standard rheological tests as often used for the characterization of brain tissue, is that it is a local test, requiring only a small volume of tissue to be homogeneous. Indentation tests are performed at different speeds and the force relaxation after a step indent is measured as well. White matter tissue is found to be stiffer than gray matter and to show more variation in response between different samples which is consistent with structural differences between white matter and gray matter. In addition to differences between white matter and gray matter, also different regions of brain tissue are compared.

Introduction

The head is often considered the most vulnerable part of the body and as a result, injuries to the head are often life-threatening or have severe consequences. In 2001, transport crashes in the EU caused up to 40 thousand deaths and over 3.3 million casualties, costing over 180 billion Euros (ETSC, 2003). To develop protective measures, an accurate assessment of injury risk is required. In the early sixties, the currently used Head Injury Criterion was developed (Versace, 1971) based on the Wayne State Tolerance Curve (Gurdjian et al., 1962). However, this criterion is based on linear head acceleration only and it does not allow for a distinction between different injury mechanisms. By using a detailed Finite Element (FE) model of the head (e.g. Bandak and Eppinger, 1994, Brands et al., 2002, Claessens et al., 1997, Horgan and Gilchrist, 2003, Kleiven, 2006, Ruan and Prasad, 1994, Willinger and Baumgartner, 2003), the behavior of the brain can be predicted for any acceleration and improved injury criteria can be developed and implemented into safety standards. Many current FE models contain a detailed geometrical description of the anatomical components but lack accurate descriptions of the mechanical behavior of the brain tissue. Whereas some FE head models differentiate between white matter and gray matter while assuming a linear viscoelastic response for both tissues, other models use a non-linear constitutive description that is equal for all tissues.

For many years, researchers have been studying the material properties of brain tissue using a variety of testing techniques (e.g. Arbogast and Margulies, 1998, Bilston et al., 2001, Brands et al., 2000, Cheng and Bilston, 2007, Estes and McElhaney, 1970, Franceschini et al., 2006, Garo et al., 2007, Miller, 1997, Miller and Chinzei, 2002, Miller, 2005, Ning et al., 2006, Peters et al., 1997, Prange and Margulies, 2002, Shen et al., 2006, Shuck and Advani, 1972, Thibault and Margulies, 1998, Velardi et al., 2006). The broad range of results for the mechanical properties, such as the storage (G) and loss modulus (G), describing the linear viscoelastic behavior, may be caused by the difference in testing methods and protocols used. Several authors have presented an overview of available literature on the constitutive properties of brain tissue, e.g. Donnely (1998), Goldsmith (1972), Ommaya (1968) and Thibault and Gennarelli (1985). A recent overview was given by Hrapko et al. (2008b), where also the effects of various test conditions on the properties obtained for brain tissue were demonstrated. Several experimental conditions were shown to affect the outcome of characterization experiments for brain tissue, such as post-mortem time, temperature and pre-compression in shear experiments (Garo et al., 2007, Hrapko et al., 2008b). In addition to experimental conditions, also variations within the tissue used for experimental characterization may exist, such as difference between species (animal brains are often used as a substitute for human brains), local anisotropy, and differences between various regions of the brain and between white matter and gray matter. The latter effects, if significantly present, could be important for future developments in finite element modeling of the head. The anisotropy of, in most cases, white matter brain tissue has been investigated by several researchers (Arbogast et al., 1995, Arbogast and Margulies, 1998, Hrapko et al., 2008b, Nicolle et al., 2004, Nicolle et al., 2005, Prange et al., 2000, Prange and Margulies, 2002), and is reported to be in the range of 30%–50%. For a discussion, see Hrapko et al. (2008b).

Although some studies have investigated differences between white matter and gray matter, some controversies remain. Only few animal studies have focussed on gray matter properties because of the gray matter regions being relatively small, which complicates standard rheological tests. White matter consists of a highly oriented fibre arrangement, whereas gray matter consists of cell bodies. It is suggested that gray matter does not have as large differences in directional properties as white matter (Prange et al., 2000, Prange and Margulies, 2002). Arbogast et al. (1995) and Arbogast and Margulies, 1997, Arbogast and Margulies, 1998 concluded that the brainstem is globally stiffer than the cerebral hemispheres and that the brainstem responds anisotropically to shear loading. Gefen and Margulies (2004) compared properties of the anterior, mid and posterior regions of the cerebrum during in vivo and in vitro indentation on the cerebral cortex. They concluded that cortical gray matter on the parietal and frontal lobes have no distinct properties. Nicolle et al. (2004) looked at directional differences of the corona radiata and found that its anisotropy is low. Gray matter from the thalamus had a larger average value for the relaxation modulus then white matter from the corpus callosum. Prange and Margulies (2002) concluded that white matter and gray matter have distinct properties. White matter behavior was more anisotropic, while gray matter was nearly isotropic. Moreover, different degrees of anisotropy exist within the white matter. Gray matter from the thalamus was slightly stiffer than white matter from corona radiata and about 30% stiffer than white matter from the corpus callosum. In contrast, Manduca et al. (2001) found white matter to be more than three times stiffer than gray matter using magnetic resonance elastography at 100 Hz. Velardi et al. (2006) found white matter to be stiffer than gray matter and found tissue from the corpus callosum to be stiffer than white matter from the corona radiata. The heterogeneity of the hippocampus was studied by Elkin et al. (2007) by atomic force microscope indentation.

Because of the inconsistency concerning differences between white matter and gray matter in the literature, also different approaches to white and gray matter stiffness variations in finite element models of the brain are found. For example, in the rat head model of Mao et al. (2006), gray matter was taken to be about 42 % stiffer than white matter, whereas in other studies (e.g. Miller et al., 1998, Al-Bsharat et al., 1999, Zhou et al., 1995) white matter was assumed to be the most stiff. Since a current trend in finite element modeling of the head is to include more and more anatomical details, such as different tissues, it is of great importance that interregional differences in mechanical properties are well understood.

An important reason for the lack of consensus about differences between the mechanical properties of different regions, and in particular white matter and gray matter, is that rheological experiments aimed at characterizing these tissues often require relatively large homogeneous samples. As a consequence, only few data on the properties of cortical gray matter exist, and some comparisons are based on gray matter from the thalamus region. In this work, indentation experiments are conducted on either white or gray matter tissue from the cerebrum and on tissue from the thalamus and the midbrain. Since, in these indentation experiments, a small region of a sample is loaded, only a relatively small homogeneous volume of tissue is required, compared to standard rheological tests. For this reason, a comparison of white matter properties and the properties of gray matter, for which only small homogeneous regions are found, becomes possible. Differences between these tissues and regional differences in terms of both mean response and variability are explored. White and gray matter samples are used from different (i.e. posterior, superior, and anterior) regions of the cerebrum, as well as from the thalamus and midbrain region. These differences are investigated for various indentation rates.

Section snippets

Sample preparation

Fresh halves of porcine brains from approximately 6 months old pigs were obtained from a local slaughterhouse. At this age, the tissue is considered to possess a fully developed microstructure (Prange and Margulies, 2002, Thibault and Margulies, 1998). Porcine brain tissue was chosen as a substitute for human brains because of availability and the possibility to minimize the post-mortem time at testing. To prevent dehydration and to slow down degradation of the tissue, the brains were placed in

Sample height

The influence of the height of the sample is determined using protocol 1 for 26 locations of white matter from different regions (corona radiata) during initial experiments. In Fig. 4, the force level obtained at indentation depths of 0.1 mm and 0.3 mm are shown. The influence of the sample height is clearly visible for the force at an indentation level of 0.3 mm. For thin samples, the glass plate of the sample dish plays a significant role when indenting up to 0.3 mm. At an indentation of

Discussion and conclusions

Many studies aimed at characterizing the mechanical properties of brain tissue have focussed on white matter material, however the properties of gray matter have been investigated to a lesser extent. One of the reasons is that gray matter regions in animal brains are often relatively small compared to white matter regions, which complicates standard rheological experiments. Consequently, some controversy exists in the literature about the difference between mechanical properties of gray and

Acknowledgements

This work has been supported by the European Integrated Project APROSYS and the Dutch Technology Foundation STW, applied science division of NWO and the Technology Program of the Ministry of Economic Affairs.

References (50)

  • G.W.M. Peters et al.

    The applicability of the time/temperature superposition principle to brain tissue

    Biorheology

    (1997)
  • K.L. Thibault et al.

    Age-dependent material properties of the porcine cerebrum: Effect on pediatric inertial head injury criteria

    Journal of Biomechanics

    (1998)
  • A.S. Al-Bsharat et al.

    Brain/skull relative displacement magnitude due to blunt head impact: New experimental data and model

    Stapp Car Crash Conference Proceedings

    (1999)
  • Arbogast, K.B., Margulies, S.S., 1997. Regional differences in mechanical properties of the porcine central nervous...
  • Arbogast, K.B., Meaney, D.F., Thibault, L.E., 1995. Biomechanical characterization of the constitutive relationship for...
  • Bandak, F.A., Eppinger, R.H., 1994. A three-dimensional finite element analysis of the human brain under combined...
  • L.E. Bilston et al.

    Large strain behavior of brain tissue in shear: Some experimental data and differential constitutive model

    Biorheology

    (2001)
  • Brands, D.W.A., Bovendeerd, P.H.M., Peters, G.W.M., Wismans, J.S.H.M., 2000. The large shear strain dynamic behavior of...
  • D.W.A. Brands et al.

    On the potential importance of non-linear viscoelastic material modelling for numerical prediction of the tissue response: Test and application

    Stapp Car Crash Journal

    (2002)
  • Claessens, M.H.A., Sauren, F., Wismans, J.S.H.M., 1997. Modelling of the human head under impact conditions: A...
  • M.A.J. Cox et al.

    Mechanical characterization of anisotropic plana biological soft tissues using large indentation: A computational feasibility study

    Journal of Biomechanical Engineering: Transactions of the ASME

    (2006)
  • Donnely, B.R., 1998. Brain tissue material properties: A comparison of results. In: Biomechanical Research:...
  • ETSC. 2003. Transport safety performance in the EU - A statistical overview. Technical Report, European Transport...
  • B.S. Elkin et al.

    Mechanical heterogeneity of the rat hippocampus measured by atomic force microscope indentation

    Journal of Neurotrauma

    (2007)
  • M.S. Estes et al.

    Response of Brain Tissue of Compressive Loading

    (1970)
  • Cited by (233)

    View all citing articles on Scopus
    View full text