Iran J Sci Technol Trans Mech Eng

https://doi.org/10.1007/s40997-018-0267-5 (0123456789().,-volV)(0123456789().,-volV)

RESEARCH PAPER

Micromechanical Modeling of the Effective Mechanical Behavior

of Cerebral Cortex Tissue
Hamid Shahsavari1 • Hossein Jokar1 • Mojtaba Haghighi-yazdi1 • Mostafa Baghani1 • Yves Remond2 •

Daniel George2 • Maryam Mazraehei Farahani3 • Majid Baniassadi1,2

Received: 29 June 2018 / Accepted: 22 October 2018

Ó Shiraz University 2018

Abstract
In this paper, a micromechanical approach is employed to propose a cerebral cortex tissue representative volume element
(RVE) and simulate the mechanical behavior of this type of tissue in different loadings. In this regard, a MATLAB code is
developed to homogenize a random distribution of neurons in the extracellular matrix. To create the RVE, different inputs
including the size of RVE, the number of neurons, the radius of the neuron cell body, the coordinates of the axon and
dendrites of a neuron, the radius of the axon and dendrites, and the minimum distance between the cellular volumes are
considered. Then, a PYTHON code is developed which generates the desired RVE in ABAQUS employing the outputs of
the MATLAB code. Also, a viscoelastic material model is considered for material components of the cerebral cortex tissue
in this study. To analyze the developed RVE, some relaxation tests are performed on the RVE. Strain rate, neuron volume
fraction (NVF), loading time and neuron distribution are investigated in different stress relaxation tests on the developed
RVEs. Considering the NVF of 1, 2 and 3%, it is concluded that the maximum tensile and compressive stresses rise by
increasing the NVF. Also, the results demonstrate that different irregular distributions of neurons have no effect on the bulk
mechanical properties of the tissue for a constant NVF and only affect the distribution of local stresses (and even the
maximum stress) in the tissue. Finally, the numerical simulations revealed that the developed RVE is a robust element
which can be employed in realistic model of the brain tissue in different loading conditions such as trauma.

Keywords Micromechanical modeling  Cerebral cortex tissue  Neuron  Extracellular matrix  Representative volume
element (RVE)

1 Introduction meantime, brain, as the most complex of living organs, has

In recent years, biomechanical engineering has been
developed to better understand the biological behavior of
living organisms (Cowin 1999; Ambrosi et al. 2017).
Determination of mechanical behavior and properties of
organs such as the brain, bone and veins is one of the most
interesting fields for biomechanical researchers. In the
& Majid Baniassadi
m.baniassadi@ut.ac.ir
1
School of Mechanical Engineering, College of Engineering,
University of Tehran, Tehran, Iran
2
ICube/CNRS, University of Strasbourg, 2 Rue Boussingault,
67000 Strasbourg, France
3
Shariati Hospital, Tehran University of Medical Sciences,
Tehran, Iran
attracted more attention. In spite of abundant researches
performed on this field, there is a lack of mechanical
modeling of the brain tissue. Mechanical damage in this
organ can lead to severe physical and mental damages or
death. Thus, it is very necessary to realistically know the
mechanical behavior of the brain tissue. The term traumatic
brain injury (TBI) refers to the sudden impact to the head
and consequently to the brain. Annually, about 1.7 million
emergency cases, hospitalizations and deaths in America
are related to this type of injury happening in different
situations such as accidents, sports and physical collisions
(Faul et al. 2010; Park et al. 2008; Sotudeh-Chafi M 2008;
Feng et al. 2013).
To achieve a better understanding mechanism of TBI,
many research groups have presented various constitutive
models and obtained numerical results. The key point for

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the development of a realistic numerical model of the brain
is the understanding of the properties of this material’s
constituents. Thus, knowing the micromechanical behavior
of the tissue in different loading conditions leads to better
understanding of TBI physics. Numerous biomechanical
studies have been performed to identify and evaluate the
mechanical properties of the brain tissue. Since this tissue
has unique complexities in microscale, such as geometrical
complexity, many researches have been conducted in a
macroscale. Accordingly, the brain tissue samples have
been tested in the different experiments such as tensile,
compressive, shear and high-frequency loadings (in vitro)
(Van Dommelen et al. 2010; Velardi et al. 2006; Prevost
et al. 2011; Budday et al. 2017; Ramo et al. 2018). In this
paper, a 3D micromechanical model of the cerebral cortex
tissue with random distribution of nerve cells in ECM is
proposed. This is an introduction to simulate the dynamic
loading applied on brain tissue like trauma. Therefore, in
the future, employing the proposed RVE in this paper,
some impact loadings (with various properties) on the brain
will be modeled in order to recognize the first place where
brain injury occurs.
Recently, hyperelastic constitutive models have been
employed to model the nonlinear mechanical behavior of
the brain tissue in large deformations. Rashid et al. (2012)
conducted high-strain-rate tensile tests on brain tissue
samples to examine the effect of the strain rate on its vis-
cous behavior. They presented a two-term Ogden consti-
tutive model for the nonlinear hyperelastic behavior of the
brain tissue and calibrated their model parameters using the
reverse finite element method and fitting the experimental
data. Feng et al. (2013) utilized dynamic shear tests on the
white matter of the brain to specify the required material
parameters in a hyperelastic model which represents the
anisotropic behavior of that matter. Laksari et al. (2012)
used compressive stress relaxation tests to develop a con-
stitutive model for finite compression. They considered a
modified Mooney–Rivlin model for volume preserving and
a two-term Ogden model for volume changing part of
deformation and calibrated the material parameters by fit-
ting the numerical results and experimental instantaneous
and equilibrium data. Also, many biomechanical resear-
ches have been performed to investigate the association
between the TBI and intensity of the stress or strain (Bain
and Meaney 2000; Bain et al. 2003; Pfister et al. 2006). In
these researches, the injury limit has been specified for
separated and intertwined axons in different loading con-
ditions. In this regard, Valdez and Balachandran (2013)
proposed a nonlinear visco-hyperelastic model to examine
the effect of material nonlinearity on the stress wave
propagation in the brain. In the following, Chatelin et al.
(2013) developed an isotropic transversely visco-hypere-
lastic constitutive model for human brain tissue.
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Iran J Sci Technol Trans Mech Eng
Employing the FE simulation of unconfined compression
tests and experimental data, they evaluated their model.
Macromechanical analysis of the brain tissue provides
knowledge of mechanical response of the brain against
external forces. Since macromechanical models cannot
predict the distribution of stress and strain between the
structural components of the brain tissue, they do not have
any understanding of the mechanisms of DAI. On the other
hand, micromechanical models can identify the influence
of each material constituent on the response of tissue. Thus,
these models have a good capability to demonstrate the
mechanism of DAI. Micromechanical finite element
methods present a robust tool to express the relationship
between the biological and mechanical behaviors (Abol-
fathi et al. 2009).
Arbogast and Margulies (1999) presented a fiber-rein-
forced composite model which includes cylindrical axons
surrounded by an extracellular matrix (ECM). Their aim
was to study the mechanical behavior of the brain stem
under the rotational force. Also, they used the Hashin
micromechanical model (1966) to assess the brain stem
linear viscoelastic behavior and presented an analytical
solution for determining the linear viscoelastic properties
of axon and ECM. Considering the viscoelastic transverse
isotropic behavior of brain stem, Ning et al. (2006) pro-
posed a unidirectional fibrous composite model for this
material. They represented the instantaneous nonlinear
elastic response of the brain stem as a hyperelastic trans-
verse isotropic behavior of a tissue. Also, they used a linear
isotropic viscoelastic model for both axons and matrix to
investigate the rate dependency of the brain tissue. Con-
sidering the effects of morphologic heterogeneities, Cloots
et al. (2008) studied the mechanical behavior of cerebral
cortex. They developed various detailed 2D FE models and
finally made a homogeneous cortex FE model. Also, they
utilized the loading conditions presented by Brands et al.
(1999). Abolfathi et al. (2009) presented a micromechani-
cal process to study the anisotropic properties of brain stem
containing viscoelastic axons surrounded by ECM. They
studied a process to determine the anisotropic behavior of
the brain white matter. Also, employing the experimental
data of Arbogast and Margulies (1999), they obtained the
viscoelastic properties of axons and ECM. Karami et al.
(2009) proposed a micromechanical finite element model
to investigate the homogenized behavior of the brain tissue
in large deformation. In this model, the brain tissue was
assumed as a fibrous composite containing axons and
anisotropic hyperelastic matrix. Utilizing adaptive kine-
matic and Ogden hyperelastic constitutive model, Pan et al.
(2011) micromechanically developed an RVE to study the
mechanical responses of axons in tissue under large tensile
deformations.
Iran J Sci Technol Trans Mech Eng

Based on what has been mentioned, many brain tissue
models have been proposed by researchers. In order to
overcome the high cost of the experimental tests in the
microscale, the micromechanical modeling is a good
choice as an alternative of laboratory tests. One of the most
important limitations of the micromechanical analysis on
the brain tissue is the lack of material behavior of its
constituents. Also, complex geometry is another important
limitation of this tissue that makes the micromechanical
modeling difficult. The time-consuming modeling and
locking of microstructure in high NVF is one of the dis-
advantages of this method. The main advantage of this
method is generalizability to examine the pattern of dam-
age, the study of brain tissue multiphysics, examination of
the TBI under various conditions and trauma examination.
In this paper, the cerebral cortex tissue is microme-
chanically investigated by presenting a realistic RVE. In
this regard, a three-dimensional geometrical model is
introduced with a more realistic model in comparison with
the previous developed models. This model is suitable for
the nonhomogeneous part of brain that has an isotropic
behavior. The proposed RVE includes randomly dis-
tributed neuron cells in a matrix in which both are vis-
coelastic. Assuming the perfect link between the
components, a homogenized finite element model is
developed for the cerebral cortex tissue using ABAQUS
6.14. In this regard, we present the micromechanical
modeling, material constitutive modeling, creating RVE
and homogenizing of the material in this paper.
irregularly distributed in the cerebral cortex and the tissue
has an isotropic property (Cloots et al. 2011, 2013). In the
proposed model, cerebral cortex tissue has been considered
as a two-phase composite which includes neuron cells as
the fillers and ECM as a basic matrix. Also, it has been
assumed that the fillers have been randomly distributed in
the basic matrix. Although this type of distribution has
complexity in analytical and geometrical modeling, more
exact results are obtained, especially in distribution of
stress and strain in tissue (Abolfathi et al. 2009).
2.1 Representative Volume Element and Finite
Element Modeling
A three-dimensional representative volume element for
cerebral cortex tissue includes the neurons that are ran-
domly distributed in the ECM. Although none of the neu-
rons have the same geometry, all of them have the same
general structure which contains three parts (as shown in
Fig. 1a): cell body, dendrites and axon. Considering these
parts, we developed a reference neuron cell model in
ABAQUS software which is depicted in Fig. 1b. In this
model, Solid3 and Beam4 elements are, respectively, used
for cell body, axons and dendrites (Documentation 2010).
Since the ratio of axon and dendrites length to its diameter

2 Micromechanical Modeling

In this section, the material behavior has been determined

employing micromechanical homogenization method
through RVE concept. In this method, the nonhomoge-
neous composite material has been substituted with an
effective fictitious homogeneous material. Many different
micromechanical models have been proposed to predict the
mechanical behavior of composite materials in the litera-
ture (Abolfathi et al. 2009; Karami et al. 2009; Yves et al.
2016; Cloots et al. 2011; Garnich and Karami 2004; Javid
et al. 2014; Nemat-Nasser and Hori 2013; Oruc-de Leon
2009). In this study, the micromechanical characterization
method, which is used to investigate composites, has been
extended to simulate the cerebral cortex tissue (Yves et al.
2016). Also, finite element method is utilized in
micromechanical modeling to examine the elastic and
viscoelastic behavior of the cerebral cortex tissue.
Various parts of the brain have different structures.
Axons have been distributed in brainstem in longitudinal
Fig. 1 a Nerve cell schematic (neuron) (https://blogs.thomsonreuters.
direction which results in transversely isotropic behavior com/answerson/history-potential-deep-learning/), b reference neuron
on the macroscale, while the nerve cells have been created in ABAQUS

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is more than ten (Braitenberg and Schüz 2013), they are
modeled by the beam element type attached to the ECM
with a perfect coupling. This element type selection results
in reducing the number of elements in RVE, and conse-
quently, computational costs are decreased. Also, cell body
is modeled as a sphere which is connected to the axon and
dendrites with a perfect coupling. Finally, the cell body is
attached to the axon and dendrites through the wire
elements.
Creating a three-dimensional RVE (Fig. 2), the random
distribution of neurons in the ECM is performed by a
mathematical code written in MATLAB. This code has
different inputs including the size of the cube side, the
number of neurons, the radius of the cellular volume, the
coordinates of axon and dendrites of a neuron, the radius of
the axons and dendrites and the minimum distance between
the cellular volumes. First, a cell body is assumed in the
center of the cube, which is considered as the center
coordinates. Then, some points, as the number of the
neurons, are randomly chosen in the cube based on speci-
fied constraints including cell–cell and cell–cube collisions.
By having these points, transformation matrices are derived
and rotation matrices are randomly assumed as the number
of them and both are applied on the axon and dendrites.
Afterward, collisions that may have occurred during the
distribution are identified and new rotation matrices are
created and applied on collided axon and dendrites. This
loop continues until no collision between two neurons is
observed and an acceptable representative volume element
would be created. Finally, reference neuron coordinate and
the transformation and rotation matrices are stored in a text
Fig. 2 Representative volume element (RVE) created in ABAQUS
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Iran J Sci Technol Trans Mech Eng
file as output. To create the model in ABAQUS software, a
PYTHON code is developed which generates the desired
representative volume elements in ABAQUS employing the
outputs of the MATLAB code.
2.2 Homogenization
The brain responses in bulk scale may vary in different
conditions such as loading condition, temperature, strain
rate as well as other physical parameters. To simulate these
responses, different material constitutive models have been
proposed including elastic, viscoelastic, hyperelastic and
poroelastic models (Ferrant 2000; Meaney 2003; Miller
and Chinzei 1997; Škrinjar 2001; Wang and Wineman
1972).
Based on the micromechanical principles, properties of
a composite material can be estimated from its components
properties and distribution. In this regard, a viscoelastic
material model is considered for material components of
the cerebral cortex tissue in this study. Firstly, both
microcomponents are considered as an elastic, homoge-
neous and isotropic material.
In the elastic analysis, the material behavior is based on
the Hooke’s law which is presented as follows:
eij ¼ S ijkl rkl ð1Þ
where rkl , eij and S ijkl are stress, strain and compliance
tensors, respectively. Equation (1) can be represented in
the Voigt form in the following form (Boresi et al. 1993):
2 3 2 32 3
e1 S11 S12 S13 S14 S15 S16 r1
6 e2 7 6 S21 S22 S23 S24 S25 S26 76 r2 7
6 7 6 76 7
6 e3 7 6 S31 S32 S33 S34 S35 S36 76 r3 7
6 7¼6 76 7 ð2Þ
6 e4 7 6 S41 S42 S43 S44 S45 S46 76 r4 7:
6 7 6 76 7
4 e5 5 4 S51 S52 S53 S54 S55 S56 54 r5 5
e6 S61 S62 S63 S64 S65 S66 r6
According to the microstructural symmetry of the tissue,
the number of compliance tensor coefficients is between 2
and 21. For instance, the number of unknown independent
coefficients of an orthotropic material is reduced to 9
(Garnich and Karami 2004).
To evaluate the viscoelastic behavior of the tissue, a
method is also used the same as elastic. In the viscoelastic
materials, the relationship between stress and strain is
expressed using an integral method presented in the fol-
lowing form:
Z t s
ts dekl
r0ij ðtÞ ¼ Cijkl
t
e0kl þ Cijkl ds; i; j; k; l ¼ 1; 2; 3 ð3Þ
0 dt
where Cijkl is the stiffness matrix and t denotes the time.
According to the above relation, the stress in the tissue at
any time depends on material behavior in history. To cal-
culate the stiffness coefficients, mechanical properties are
Iran J Sci Technol Trans Mech Eng

considered as constants in each incremental time of simu- (directional and rotational) of a face of RVE are fixed and a
lation. Thus, we can discretize the integral in Eq. (3). In shear displacement is applied on its parallel face.
this study, the relaxation test is employed to analyze where In this study, the RVE is considered as orthotropic
the strain is constant and stress relaxes over the time. It is material in which compliance tensor has nine unknown
noteworthy to mention that Eq. (3) can be represented in coefficients. Nine independent equations are needed in
the Voigt form as: order to determine these coefficients. In this regard, six
2 3 2 t t t t t t 32 0 3 kinematic loadings on RVE, including three compressive
r11 C11 C12 C13 C14 C15 C16 e11
6 r 7 6 Ct t
C22 t
C23 t
C24 t
C25 t 76 0 7
C26 and three shear loadings, can lead to obtaining these
6 22 7 6 21 76 e22 7
6 7 6 t t t t t t 7 6 7 equations. To solve these equations, applied stress and
6 r33 7 6 C31 C32 C33 C34 C35 C36 76 e033 7
6 7 6 76 7
6 r 7 ¼ 6 Ct t
C42 t
C43 t
C44 t
C45 t 76 0 7
C46 76 e23 7
strain on the RVE should be calculated after loading. Thus,
6 23 7 6 41
6 7 6 t t 7 6 7 a PYTHON code is developed in ABAQUS software to
4 r31 5 4 C51 t
C52 t
C53 t
C54 t
C55 C56 54 e031 5
t t t t t t determine mean volumetric stress and strain values which
r12 C61 C62 C63 C64 C65 C66 e012
2 ts ts 32
 3 are presented in the following forms:
C11 C12 ts ts
C13 ts
C14 ts
C15 C16 des11 dt Z
6 C ts C ts ts ts ts ts 76 s
 7 1
6 21 22 C23 C24 C25 C26 76 de22 dt 7 hri ¼ rm dv ð5Þ
Z t 6 ts ts 7 6 7 V V
6 C31 C32 ts ts
C33 ts
C34 ts
C35 C36 76 des33 dt 7
þ 6 76  7ds Z
6 ts C ts ts ts ts ts 76 s 7
0 6 C41 42 C43 C44 C45 C46 76 de23 dt 7 1
6 ts ts 7 6 s 7 hei ¼ em dv ð6Þ
4 C51 C52 ts ts
C53 ts
C54 ts
C55 C56 5 4 de31 dt 5 V V

ts
C61 ts
C62 ts
C63 ts
C64 ts
C65 C66ts
des12 dt
where V is the RVE total volume. hri and hei are,
ð4Þ
respectively, mean volumetric (macroscopic) stress and
Shear and compressive experiments are needed in order strain. Also, rm and em are local (microscopic) stress and
to study the viscoelastic behavior and characterization of strain, respectively. Since the reported stress and strain by
the desired tissue. In these tests, a constant strain, which the ABAQUS software are in the local coordinate, we
should not exceed 5% to correctly assume infinitesimal should calculate these variables in global coordinate in
strain, is applied on the RVE (Abolfathi et al. 2009). In the order to use Eqs. (5) and (6). Thus, Eq. (7) is utilized to
compressive tests, a compressive displacement is applied rotate the stress tensor into global coordinate.
on a side of RVE and its opposite side is fixed in all
½r ¼ ½T ½r0 ½Tt  ð7Þ
directions and rotations. In addition, two nonparallel sides
from the remaining four sides are fixed in perpendicular r and r0 are, respectively, stress tensors in global and local
direction (see Fig. 3). These boundary conditions have coordinates and also T t is the transposition of rotation
been introduced by Shaoning (2014) that lead to appro- tensor that is presented in Eq. (8) in the following form:
priate results. In shear tests, all freedom degrees 2 3
cos /1 cos U  sin /1 cos /1 sin U
½T  ¼ 4 sin /1 cos U cos /1 sin /1 sin U 5 ð8Þ
 sin U 0 cos U
where U and /1 are depicted in Fig. 4 as follows (Mazrouei
et al. 2014):

Fig. 3 Implemented boundary conditions on RVE Fig. 4 Relation between local and global coordinates

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3 Results and Discussion

In this section, various analyses have been conducted and

the results have been evaluated. Elastic properties of the
ECM and neuron, as cerebral cortex tissue constituents, are
listed in Table 1.
Viscoelastic analysis is performed utilizing ABAQUS
software in which time increments are large where stress
drop is high. Although loading time at some simulations is
considered 0.1 s, many simulations are developed with
various time increments to investigate the rate dependency
behavior of the cerebral cortex tissue. Time domain model
is used in ABAQUS software to define the viscoelastic
properties. Equation (9) presented the Prony series used to Fig. 5 Effect of the RVE size with volume fraction of 1.5% on tissue
define the shear modulus in the viscoelastic analysis as properties
follows:
! Since the brain tissue in some areas, especially in its
Xn
GðtÞ ¼ G0 1  gk ð1  et=sk Þ ð9Þ cerebral cortex, shows the isotropic behavior, it is neces-
k¼1 sary to investigate the isotropy of the model (Cloots et al.
2011; Cloots and van Dommelen 2011). Due to the fact
where sk is relaxation time and its corresponding relaxed
that the random distribution is employed in the creation of
shear modulus is G0  gk . Also, viscoelastic properties of
the RVE, it is expected that the proposed model will pre-
the constituents are tabulated in Table 2.
sent the isotropic behavior. In this regard, an RVE with
In the proposed model, the diameter of neuron cell, the
dimension of 300 lm and NVF of 3% are developed. Ini-
diameter of axon and dendrites, the length of axons and the
tially, orthotropic behavior is assumed for the tissue and
length of dendrites are 50 lm, 1.5 lm, 300 lm and 55 lm,
elastic and shear moduli are calculated (see Table 3). As
respectively. It is noteworthy to mention that the size of
observed in Table 3, there is a slight difference between
RVE has a crucial effect on results in micromechanical
the results in different directions. Thus, the RVE represents
analysis. Thus, selecting nonproper size, boundary condi-
an isotropic behavior which means that the mechanical
tions may influence the results. Elastic analysis is
properties of the model are independent of direction.
employed to select the appropriate size of RVE, and the
Since each of the elastic shear moduli in three directions
results of many RVE with different sizes are compared by
is approximately equal, it is concluded that the behavior of
considering a fixed NVF.
isotropic elements is representative of the volume. Also,
Figure 5 depicts the elastic modulus of some RVE with
utilizing this cellular model, there is no need to consider
the NVF of 1.5% for various sizes of 300 lm, 400 lm,
700 lm, 900 lm and 1100 lm. As observed in this figure,
the RVE with size of 900 lm is a suitable choice, since by Table 3 Obtained mechanical properties of the cerebral cortex tissue
increasing the size of RVE more than that, there is no any with neuron volume fraction of 3%
change in elastic modulus.
Direction Young modulus Shear modulus (Pa) Poisson
(Pa) ratio

X 2085.258 – –
Table 1 Elastic properties of the cerebral cortex tissue constituents
(Abolfathi et al. 2009) Y 2083.528 – –
Z 2084.753 – –
Elastic modulus (Pa) Poisson ratio
XY – 698.612 0.492
Neuron 6160 0.4999 XZ – 697.736 0.495
ECM 2040 0.4999 YZ – 697.123 0.496

Table 2 Viscoelastic properties

Instantaneous modulus (Pa) Poisson ratio g1 s1 (s) g2 s2 (s)
of the cerebral cortex tissue
constituents (Javid et al. 2014) Neuron 12,860 0.5 0.6039 0.60097 0.1083 0.49866
ECM 4290 0.5 0.50001 0.00623 0.25986 0.9

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Iran J Sci Technol Trans Mech Eng
numerous experiments and mechanical properties of the
tissue can be obtained using two types of tests.
Following the selection of an appropriate RVE, the
effect of NVF on the mechanical behavior of the cerebral
cortex tissue is investigated. As shown in Fig. 6, the vol-
ume fraction is varied between 1% and 4%. Neuron cells
are depicted in different colors to better see the distribu-
tion. As observed in Fig. 7, the elastic modulus is raised by
increasing the volume fraction of neurons. Due to the low
Fig. 6 RVE with dimension of 900 lm with the NVF of a 1%, b 2%, c 3% and d 4%
ratio of diameter to length (aspect ratio) of neuron cells,
there is no significant change in elastic modulus in different
volume fractions. It is noteworthy to mention that the
volume ratio of axon and dendrites to volume cell is very
low. Abolfathi et al. (2009) reported that in areas of the
brain such as the stem, where only axons are surrounded by
the ECM, increasing the volume fraction of axons leads to
enhancement of the elastic modulus.
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Fig. 7 Effect of NVF on elastic modulus of the cerebral cortex tissue
Also, they reported that in areas of brain where the
volume cell has less volume and axons possess higher
volume in a neuron cell, increasing the neuron cell volume
fraction can significantly increase the mechanical proper-
ties such as elastic modulus. In most empirical and
numerical studies in the field of composites for distributing
dilute particles, the results of homogeneous mechanical
properties are closer to the lower band, and here too this is
true.
A comparison between Ex obtained from the finite ele-
ment results of the elastic analysis and lower bound (Reuss
model) and upper bound (Voigt model) (Pierard et al.
2004), which are used for composite materials, is depicted
in Fig. 8. The proposed model represents logical behavior,
since its results are between lower and upper bounds.
This comparison also shows that the obtained properties
are closer to the lower bound, due to the low aspect ratio of
axons and dendrites. Due to the differences in the geometry
and density of the constituents in different parts of the
brain, elastic and shear moduli are different in various parts
Fig. 8 Comparison of Ex obtained from finite element results and
upper bound (Voigt) and lower bound (Reuss)
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Iran J Sci Technol Trans Mech Eng
Table 4 Young modulus for two RVEs with NVF of 2% and different
random distribution
Mechanical properties (Pa) First distribution Second distribution
Ex 2070.499 2069.533
Ey 2067.772 2068.249
Ez 2068.683 2067.231
of tissues. Thus, the different regions of the brain should be
sampled and analyzed to obtain its mechanical properties.
To investigate the effect of irregular distribution of
neurons in the ECM on the mechanical properties of the
cerebral cortex tissue, two RVEs with the NVF of 2% and
different random distributions are developed. The simula-
tion results in Table 4 demonstrate that the mechanical
properties of these RVEs are close and the random distri-
bution of neurons in the cerebral cortex tissue has no sig-
nificant effect on the overall properties of the tissue.
Considering an RVE with the NVF of 3% under com-
pressive loading, Fig. 9 shows von Mises stress contour of
a neuron.
Also, Fig. 10 demonstrates the stress contours of the
neurons in X direction for an RVE with the NVF of 3%. In
most models of the brain tissue, the maximum von Mises
stress in the RVE is at the junction of the volume cell and
axon as well as dendrites. Diffuse axonal injury (DAI) is
one of the most common brain damages where nerve cells
and axons are damaged (Przekwas et al. 2016). Existence
of maximum stress in these regions is a confirmation of
DAI.
After the elastic analysis, the viscoelastic behavior is
analyzed. In this regard, a constant strain is applied on an
RVE with the NVF of 2%. Figure 11 shows the applied
strain on RVE to simulate the relaxation test. As observed,
the mean strain calculated from finite element results is
equal to the applied strain.
Figure 12a, b demonstrates the stress value with respect
to the time for loading in x and y directions, respectively.
As observed in these figures, raising the NVF leads to
increment of the stresses. Also, rising stress in first 0.1 s is
due to the applied strain. Since the relaxation test is con-
ducted on the model, strain remains constant after applying
1% of strain. When the strain is fixed, the stress starts to
relax and it is completely relaxed in 5 s. As observed, by
increasing the NVF, the maximum and relaxed stresses are
raised and the RVE responds stiffer. This slight increasing
in stiffness is due to the low aspect ratio in neurons, as
discussed in the elastic modulus analysis.
The other item which is changed by increasing the NVF
is the relaxation time in this type of loading. Assuming that
neurons have less relaxation time than the ECM, it is
expected that the cerebral cortex tissue relaxation time
Iran J Sci Technol Trans Mech Eng

Fig. 9 von Mises stress contour of neuron after compressive load on RVE

Fig. 10 Stress contour in the x direction in RVE after compression

decreases by increasing the NVF. Since the neurons and

0.012 ECM have almost the same relaxation time, no specific
changes are seen by varying the NVF.
0.01
In the relaxation tests, the rate of applied strain is one of
0.008 the important parameters in loading. The strain rate should
0.006
be less than relaxation time (s) to obtain a reliable result.
e11

Considering the results shown in previous figures, the

0.004
relaxation time is about 3 s. Since the time of applied strain
0.002 is 0.1 s, this relaxation test is reliable in terms of loading
0
time.
0 1 2 3 4 5 6 Figure 13a–c, respectively, shows von Mises, maximum
Time (s) tensile and maximum compressive stresses of tissue with
neuron volume fractions of 1, 2 and 3% under loading in
Fig. 11 exx of RVE with the NVF of 2% under loading
the x direction. It is obvious that the maximum tensile
stress in the loading direction has risen by increasing the

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 Iran J Sci Technol Trans Mech Eng

25
25

20
20

15 15

S22 (Pa)
VF1 VF1
S11 (Pa)

VF2 VF2
10 10
VF3 VF3

5 5

0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Time (s) Time (s)
(a) (b)
Fig. 12 a rxx and b ryy of RVE with the NVF of 1, 2 and 3% under loading in x and y directions

200 1200
180
160 1000
140
800

S11,max (Pa)
120
Smises (Pa)

100 VF1 600 VF1

80 VF2 VF2
60 400
VF3 VF3
40
200
20
0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Time (s) Time (s)
(a) (b)
1200

1000

800
S11,max (Pa)

600 VF1
VF2
400
VF3
200

0
0 1 2 3 4 5 6
Time (s)

(c)
Fig. 13 a von Mises stress and maximum, b tensile rxx and c compressive rxx of tissue with neuron volume fractions of 1, 2 and 3% under
loading in the x direction

NVF. Also, the maximum tensile and compressive stresses
do not have a great loss. Since the neuron distribution in
the RVE with the NVF of 3% is denser than two other
NVF, increase in maximum tensile and compressive
stresses in NVF of 3% is larger than others.
To investigate the effect of strain rate on tissue, an RVE
with the NVF of 2% is considered. This element is loaded
under four compressive loadings (1% strain) in the x di-
rection with loading times of 0.05, 0.1, 0.2 and 0.3 (s). The
applied compressive strains for these four loadings are
demonstrated in Fig. 14a. This figure shows that the
relaxed strain is the same in all loading times. Also,
Fig. 14b shows the mean volume stress in the RVE for four
different strain rate loadings. It is observed that the mean
volume stress increases by increasing the strain rate and the
mean stress tends to a specific value in all loadings due to a
constant NVF. The maximum von Mises stress in the RVE
in the first 5 s is demonstrated in Fig. 14c. Considering this
figure, the maximum von Mises stresses have risen by
increasing the strain rate. These stresses are relaxed to a
specific value and their relaxation times are almost equal.
Also, it is obvious that the brain tissue is very vulnerable in
trauma when there is a high strain rate. Figure 14d and
e depicts the maximum tensile and compressive stress in
the x direction, respectively. It is revealed that the com-
pressive stress is higher than tensile stress and relaxed to a
specific value. In all of these figures, the relaxed stresses
are the same.
As the last analysis, the effects of neurons distribution
on maximum tensile and compressive stress in the loading

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0.012

0.01 30

25
0.008
0.05 20

Smean (Pa)
0.006 0.05
e11

0.1 15
0.1
0.004 0.2
10 0.2
0.3
0.002 0.3
5

0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Time (s) Time (s)
(a) (b)
1000
250 900
800
200 700

S11,max (Pa)
600
Smises (Pa)

150 0.05
0.05 500
400 0.1
100 0.1
300 0.2
0.2
50 200 0.3
0.3
100
0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Time (s) Time (s)
(c) (d)
1200

1000

800
S11,max (Pa)

0.05
600
0.1
400 0.2
200 0.3

0
0 1 2 3 4 5 6
Time (s)
(e)

Fig. 14 a Applied strain on the model for different durations of d corresponding maximum tensile stresses in the x direction and
0.05 s, 0.1 s, 0.2 s and 0.3 s, b corresponding mean volumetric e corresponding maximum compressive stresses in the x direction
stresses in the x direction, c corresponding von Mises stresses,

direction and also von Mises stress are investigated. Fig-
ure 15a shows the von Mises stress in a relaxation test for
three different neuron distributions where there is not any
reason for being equal von Mises stress. In this figure, von
Mises stresses have markedly declined but relaxed to a
specific value in each distribution. Figure 15b, c demon-
strates the maximum tensile and compressive stresses in
the x direction for three different neuron distributions,
respectively. It is observed that maximum stresses are
different and the stresses have no sharp drop in both charts.
Also, great difference between two distributions in maxi-
mum tensile stress is not a reason to repeat the same
behavior for the maximum compressive stress where the
corresponding compressive stresses have less difference.
Finally, the results demonstrate that although different
irregular distributions of neurons have no effect on the
mechanical properties of the tissue in a constant NVF, this
difference can affect the distribution of local stresses (and
even the maximum stress) in the tissue.
4 Conclusion
In this paper, a three-dimensional micromechanical
homogenized RVE of the cerebral cortex tissue considering
random distributed nerve cells in the ECM was developed.
This is a computational tool to simulate the actual loading
applied on brain tissue like trauma. The primary goal of
this research was to propose a representative volume ele-
ment (RVE) for cerebral cortex tissue by considering the
nerve cells embedded in the ECM. The RVE was modeled
along with details of nerve cells including volume cell
meshed by 3D elements and axon and dendrites meshed by
3D beam elements. Also, two viscoelastic models were

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 Iran J Sci Technol Trans Mech Eng

200 1200
180
160 1000
140 800

S11,max (Pa)
120
Smises (Pa)

100 Generation1 600 Generation1

80 Generation2 Generation2
60 400
Generation3 Generation3
40 200
20
0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Time (s) Time (s)

(a) (b)
1200

1000

800
S11,max (Pa)

600 Generation1
Generation2
400
Generation3
200

0
0 1 2 3 4 5 6
Time (s)
(c)
Fig. 15 a von Mises stress and maximum, b tensile rxx and c compressive rxx of tissue with the NVF of 2% under loading in the x direction for
three different distributions of neurons in the ECM

assigned to neurons and ECM. To create an RVE without
any collision between nerve cells, a MATLAB code was
developed to distribute the nerve cells in the matrix. Then,
a PYTHON code was developed to simulate the RVE
employing the produced neuron’s geometry and coordinate
by the MATLAB code. After simulation of some RVE with
the neuron volume fraction (NVF) of 1.5% for various
sizes of 300 lm, 400 lm, 700 lm, 900 lm and 1100 lm,
it was concluded that the RVE with size of 900lm is a
suitable choice.
The effects of some parameters such as NVF, strain rate
loading and neurons distribution on the mechanical
behavior of the cerebral cortex tissue RVE were investi-
gated. Three relaxation tests were performed on the RVE
with the NVF of 1, 2 and 3%. The maximum tensile and
compressive stress in the loading direction rose by
increasing the NVF. Since the neuron distribution in the
RVE with the NVF of 3% was denser than two others,
increasing in maximum tensile and compressive stresses in
NVF of 3% was larger than others. In the following, four
compressive relaxation loadings (1% strain), in which
loading times were 0.05, 0.1, 0.2 and 0.3 (s), were applied
on an RVE with the NVF of 2%. The mean volume stresses
and the maximum von Mises stresses rose by increasing the
strain rate, and both of them relaxed to a specific value in
all loadings due to a constant NVF. Also, it was concluded
that the cerebral cortex tissue is very sensitive in trauma
when there is a high strain rate. Finally, the neurons
distribution effect on maximum tensile and compressive
stress and also von Mises stress was studied. von Mises
stress markedly dropped but relaxed to a specific value in
each distribution. In contrast, maximum stresses had
slightly decreased in both tensile and compressive cases.
Although different irregular distributions of neurons had no
effect on the bulk mechanical properties of the tissue with a
constant NVF, this difference could affect the maximum
local stress in the tissue.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
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