Mechanical characterisation of brain tissue up to 35% strain at 1, 10, and 100/s using a custom-built micro-indentation apparatus.

Understanding the behaviour of soft tissues under large strains and high loading rates is crucial in the field of biomechanics in order to investigate tissue behaviour during pathological processes such as traumatic brain injury (TBI). It is, therefore, necessary to characterise the mechanical properties of such tissues under large strain and high strain rates that are similar to those experienced during injury. However, there is a dearth of large strain and high rate mechanical properties for brain tissue. This is likely driven by the lack of commercially available equipment to perform such tests and the difficulties associated with developing appropriate custom-built apparatus. Here, we address this problem by presenting a novel, custom-built micro-indentation apparatus that is capable of characterising the mechanical properties of brain tissue up to 35% at 100/s with a spatial resolution of 250 µm. Indentations were performed on the cortex and cerebellum of five-week-old mouse brains up to 35% strain at 1, 10, and 100/s. Three hyperelastic models were fitted to the experimental data that demonstrate the strong rate-dependency of the tissue. The neo-Hookean shear modulus for the cortex tissue was calculated to be 2.36 ± 0.46, 3.64 ± 0.48, and 8.98 ± 0.66 kPa (mean ± SD) for 1, 10, and 100/s, respectively. Similarly, the cerebellum shear modulus was calculated to be 1.12 ± 0.26, 1.58 ± 0.32, 3.10 ± 0.70 kPa for 1, 10, and 100/s, respectively. Student's t-tests were used to show statistically significant differences between the cortex and cerebellum at each strain rate. Furthermore, we discuss the apparent strain-softening effect in the 100/s force-displacement curves for both regions after approximately 30% strain.

[1]  Ming Shen,et al.  A comprehensive experimental study on material properties of human brain tissue. , 2013, Journal of biomechanics.

[2]  Jochen Guck,et al.  Viscoelastic properties of individual glial cells and neurons in the CNS , 2006, Proceedings of the National Academy of Sciences.

[3]  A F Mak,et al.  Estimating the effective Young's modulus of soft tissues from indentation tests--nonlinear finite element analysis of effects of friction and large deformation. , 1997, Medical engineering & physics.

[4]  S. Kleiven,et al.  Consequences of head size following trauma to the human head. , 2002, Journal of biomechanics.

[5]  M. Gilchrist,et al.  Mechanical characterization of brain tissue in tension at dynamic strain rates. , 2020, Journal of the mechanical behavior of biomedical materials.

[6]  R. Ogden Large deformation isotropic elasticity – on the correlation of theory and experiment for incompressible rubberlike solids , 1972, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[7]  B. Morrison,et al.  Age-dependent regional mechanical properties of the rat hippocampus and cortex. , 2010, Journal of biomechanical engineering.

[8]  B Pierrat,et al.  Indentation of heterogeneous soft tissue: Local constitutive parameter mapping using an inverse method and an automated rig. , 2018, Journal of the mechanical behavior of biomedical materials.

[9]  Daan Nieboer,et al.  Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis. , 2016, The Lancet. Public health.

[10]  M A Forero Rueda,et al.  Comparative multibody dynamics analysis of falls from playground climbing frames. , 2009, Forensic science international.

[11]  Michael D. Gilchrist,et al.  The creation of three-dimensional finite element models for simulating head impact biomechanics , 2003 .

[12]  G. Box,et al.  On the Experimental Attainment of Optimum Conditions , 1951 .

[13]  I. Sack,et al.  Measurement of the hyperelastic properties of ex vivo brain tissue slices. , 2011, Journal of biomechanics.

[14]  R. J. Atkin,et al.  An introduction to the theory of elasticity , 1981 .

[15]  D. MacManus,et al.  An empirical measure of nonlinear strain for soft tissue indentation , 2017, Royal Society Open Science.

[16]  F. Pervin,et al.  Effect of inter-species, gender, and breeding on the mechanical behavior of brain tissue , 2011, NeuroImage.

[17]  M. Wald,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002-2006 , 2010 .

[18]  M. Gilchrist,et al.  Mechanical characterization of brain tissue in simple shear at dynamic strain rates. , 2020, Journal of the mechanical behavior of biomedical materials.

[19]  M. Ortiz,et al.  Biomechanics of traumatic brain injury , 2008 .

[20]  R. Rivlin Large elastic deformations of isotropic materials IV. further developments of the general theory , 1948, Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences.

[21]  E. Kuhl,et al.  Mechanical properties of gray and white matter brain tissue by indentation. , 2015, Journal of the mechanical behavior of biomedical materials.

[22]  N. Colgan,et al.  Applying DTI white matter orientations to finite element head models to examine diffuse TBI under high rotational accelerations. , 2010, Progress in biophysics and molecular biology.

[23]  B. Morrison,et al.  Dynamic, regional mechanical properties of the porcine brain: indentation in the coronal plane. , 2011, Journal of biomechanical engineering.

[24]  Weinong W Chen,et al.  Dynamic mechanical response of bovine gray matter and white matter brain tissues under compression. , 2009, Journal of biomechanics.

[25]  H. Budka,et al.  Brain Protein Preservation Largely Depends on the Postmortem Storage Temperature: Implications for Study of Proteins in Human Neurologic Diseases and Management of Brain Banks: A BrainNet Europe Study , 2007, Journal of neuropathology and experimental neurology.

[26]  M. LaPlaca,et al.  Neural mechanobiology and neuronal vulnerability to traumatic loading. , 2010, Journal of biomechanics.

[27]  Clifford R. Jack,et al.  Magnetic resonance elastography of the brain , 2008, NeuroImage.

[28]  R. Sinkus,et al.  Viscoelastic properties of human cerebellum using magnetic resonance elastography. , 2011, Journal of biomechanics.

[29]  M. Gilchrist,et al.  Mechanical characterization of the P56 mouse brain under large-deformation dynamic indentation , 2016, Scientific Reports.

[30]  Frederico A. C. Azevedo,et al.  Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled‐up primate brain , 2009, The Journal of comparative neurology.

[31]  G. Lubec,et al.  Postmortem Changes in the Level of Brain Proteins , 2001, Experimental Neurology.

[32]  D F Meaney,et al.  Defining brain mechanical properties: effects of region, direction, and species. , 2000, Stapp car crash journal.

[33]  D. K. Cullen,et al.  Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal–astrocytic co-cultures , 2007, Brain Research.

[34]  M. Gilchrist,et al.  Fall and injury incidence rates of jockeys while racing in Ireland, France and Britain. , 2010, Injury.

[35]  M. Gilchrist,et al.  Mechanical characterization of brain tissue in compression at dynamic strain rates. , 2012, Journal of the mechanical behavior of biomedical materials.

[36]  L. Sundstrom,et al.  A tissue level tolerance criterion for living brain developed with an in vitro model of traumatic mechanical loading. , 2003, Stapp car crash journal.

[37]  D. Meaney,et al.  Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury. , 2000, Journal of biomechanical engineering.

[38]  Blaine Hoshizaki,et al.  An examination of American football helmets using brain deformation metrics associated with concussion , 2013 .

[39]  J. van Dommelen,et al.  The influence of test conditions on characterization of the mechanical properties of brain tissue. , 2008, Journal of biomechanical engineering.

[40]  Guy M. McKhann,et al.  Regional mechanical properties of human brain tissue for computational models of traumatic brain injury. , 2017, Acta biomaterialia.

[41]  M. Gilchrist,et al.  Protection of cortex by overlying meninges tissue during dynamic indentation of the adolescent brain. , 2017, Acta biomaterialia.

[42]  Ralph Sinkus,et al.  In vivo brain viscoelastic properties measured by magnetic resonance elastography , 2008, NMR in biomedicine.

[43]  King H. Yang,et al.  Development of a finite element human head model partially validated with thirty five experimental cases. , 2013, Journal of biomechanical engineering.

[44]  S. Cescotto,et al.  Experimental verification of brain tissue incompressibility using digital image correlation. , 2011, Journal of the mechanical behavior of biomedical materials.

[45]  Thibault P. Prevost,et al.  Biomechanics of single cortical neurons. , 2010, Acta biomaterialia.

[46]  David K. Menon,et al.  Changing patterns in the epidemiology of traumatic brain injury , 2013, Nature Reviews Neurology.

[47]  H. Ahmadzadeh,et al.  Viscoelasticity of tau proteins leads to strain rate-dependent breaking of microtubules during axonal stretch injury: predictions from a mathematical model. , 2014, Biophysical journal.

[48]  Peter J Hellyer,et al.  Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology , 2017, Brain : a journal of neurology.

[49]  C. Birkl,et al.  Mechanical characterization of human brain tissue. , 2017, Acta biomaterialia.

[50]  Hui Zhao,et al.  Material Properties and Constitutive Modeling of Infant Porcine Cerebellum Tissue in Tension at High Strain Rate , 2015, PloS one.

[51]  S. Kleiven Predictors for traumatic brain injuries evaluated through accident reconstructions. , 2007, Stapp car crash journal.

[52]  L. Thibault,et al.  Anin vitro traumatic injury model to examine the response of neurons to a hydrodynamically-induced deformation , 1997, Annals of Biomedical Engineering.

[53]  Barclay Morrison,et al.  Viscoelastic Properties of the Rat Brain in the Sagittal Plane: Effects of Anatomical Structure and Age , 2011, Annals of Biomedical Engineering.

[54]  Barclay Morrison,et al.  Non-ideal effects in indentation testing of soft tissues , 2014, Biomechanics and modeling in mechanobiology.

[55]  Ken Gall,et al.  In Vivo Penetration Mechanics and Mechanical Properties of Mouse Brain Tissue at Micrometer Scales , 2009, IEEE Transactions on Biomedical Engineering.

[56]  Javier DeFelipe,et al.  The Evolution of the Brain, the Human Nature of Cortical Circuits, and Intellectual Creativity , 2011, Front. Neuroanat..

[57]  E Kuhl,et al.  Brain stiffness increases with myelin content. , 2016, Acta biomaterialia.

[58]  Michelle C LaPlaca,et al.  High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model. , 2005, Journal of biomechanics.

[59]  Takeo Matsumoto,et al.  Mechanical Characterization of Brain Tissue in High-Rate Compression , 2007 .

[60]  M. Gilchrist,et al.  A viscoelastic analysis of the P56 mouse brain under large-deformation dynamic indentation. , 2017, Acta biomaterialia.