Fitted hyperelastic parameters for Human brain tissue from reported tension,compression, and shear tests

The mechanical properties of human brain tissue are the subject of interest because of their use in understanding brain trauma and in developing therapeutic treatments and procedures. To represent the behavior of the tissue, we have developed hyperelastic mechanical models whose parameters are fitted in accordance with experimental test results. However, most studies available in the literature have fitted parameters with data of a single type of loading, such as tension, compression, or shear. Recently, Jin et al. (Journal of Biomechanics 46:2795−2801, 2013) reported data from ex vivo tests of human brain tissue under tension, compression, and shear loading using four strain rates and four different brain regions. However, they do not report parameters of energy functions that can be readily used in finite element simulations. To represent the tissue behavior for the quasi-static loading conditions, we aimed to determine the best fit of the hyperelastic parameters of the hyperfoam, Ogden, and polynomial strain energy functions available in ABAQUS for the low strain rate data, while simultaneously considering all three loading modes. We used an optimization process conducted in MATLAB, calling iteratively three finite element models developed in ABAQUS that represent the three loadings. Results showed a relatively good fit to experimental data in all loading modes using two terms in the energy functions. Values for the shear modulus obtained in this analysis (897−1653 Pa) are in the range of those presented in other studies. These energy-function parameters can be used in brain tissue simulations using finite element models.     

Bidirectional hyperelastic characterization of brain white matter tissue

Biomechanics and Modeling in Mechanobiology - Biomechanical study of brain injuries originated from mechanical damages to white matter tissue requires detailed information on mechanical...     

Adjoint multi-start-based estimation of cardiac hyperelastic material parameters using shear data

Cardiac muscle tissue during relaxation is commonly modeled as a hyperelastic material with strongly nonlinear and anisotropic stress response. Adapting the behavior of such a model to experimental or patient data gives rise to a parameter estimation problem which involves a significant number of parameters. Gradient-based optimization algorithms provide a way to solve such nonlinear parameter estimation problems with relatively few iterations, but require the gradient of the objective functional with respect to the model parameters. This gradient has traditionally been obtained using finite differences, the calculation of which scales linearly with the number of model parameters, and introduces a differencing error. By using an automatically derived adjoint equation, we are able to calculate this gradient more efficiently, and with minimal implementation effort. We test this adjoint framework on a least squares fitting problem involving data from simple shear tests on cardiac tissue samples. A second challenge which arises in gradient-based optimization is the dependency of the algorithm on a suitable initial guess. We show how a multi-start procedure can alleviate this dependency. Finally, we provide estimates for the material parameters of the Holzapfel and Ogden strain energy law using finite element models together with experimental shear data.     

Measurement of the hyperelastic properties of ex vivo brain tissue slices

The elastic and hyperelastic properties of brain tissue are of interest to the medical research community as there are several applications where accurate characterization of these properties is crucial for an accurate outcome. The linear response is applicable to brain elastography, while the non-linear response is of interest for surgical simulation programs. Because of the biological differences between gray and white matter, it is reasonable to expect a difference in their mechanical properties. The goal of this work is to characterize the elastic and hyperelastic properties of the brain gray and white matter. In this method, force-displacement data of these tissues were acquired from 25 different brain samples using an indentation apparatus. These data were processed with an inverse problem algorithm using finite element method as the forward problem solver. Young's modulus and the hyperelastic parameters corresponding to the commonly used Polynomial, Yeoh, Arruda-Boyce, and Ogden models were obtained. The parameters characterizing the linear and non-linear mechanical behavior of gray and white matters were found to be significantly different. Young's modulus was 1787±186 and 1195±157Pa for white matter and gray matter, respectively. Among hyperelastic models, due to its accuracy, fewer parameters and shorter computational time requirements, Yeoh model was found to be the most suitable. Due to the significant differences between the linear and non-linear tissue response, we conclude that incorporating these differences into brain biomechanical models is necessary to increase accuracy.     

A comprehensive experimental study on material properties of human brain tissue

A comprehensive study on the biomechanical response of human brain tissue is necessary to investigate traumatic brain injury mechanisms. Published brain material property studies have been mostly performed under a specific type of loading, which is insufficient to develop accurate brain tissue constitutive equations. In addition, inconsistent or contradictory data in the literature made it impossible for computational model developers to create a single brain material model that can fit most, if not all, experimental results.     

Anisotropic and hyperelastic identification of in vitro human arteries from full-field optical measurements

In this paper, we present a new approach for the bi-axial characterization of in vitro human arteries and we prove its feasibility on an example. The specificity of the approach is that it can handle heterogeneous strain and stress distributions in arterial segments. From the full-field experimental data obtained in inflation/extension tests, an inverse approach, called the virtual fields method (VFM), is used for deriving the material parameters of the tested arterial segment. The obtained results are promising and the approach can effectively provide relevant values for the anisotropic hyperelastic properties of the tested sample.     

Calibration of hyperelastic material properties of the human lumbar intervertebral disc under fast dynamic compressive loads

Under fast dynamic loading conditions (e.g. high-energy impact), the load rate dependency of the intervertebral disc (IVD) material properties may play a crucial role in the biomechanics of spinal trauma. However, most finite element models (FEM) of dynamic spinal trauma uses material properties derived from quasi-static experiments, thus neglecting this load rate dependency. The aim of this study was to identify hyperelastic material properties that ensure a more biofidelic simulation of the IVD under a fast dynamic compressive load. A hyperelastic material law based on a first-order Mooney-Rivlin formulation was implemented in a detailed FEM of a L2-L3 functional spinal unit (FSU) to represent the mechanical behavior of the IVD. Bony structures were modeled using an elasto-plastic Johnson-Cook material law that simulates bone fracture while ligaments were governed by a viscoelastic material law. To mimic experimental studies performed in fast dynamic compression, a compressive loading velocity of 1 m/s was applied to the superior half of L2, while the inferior half of L3 was fixed. An exploratory technique was used to simulate dynamic compression of the FSU using 34 sets of hyperelastic material constants randomly selected using an optimal Latin hypercube algorithm and a set of material constants derived from quasi-static experiments. Selection or rejection of the sets of material constants was based on compressive stiffness and failure parameters criteria measured experimentally. The two simulations performed with calibrated hyperelastic constants resulted in nonlinear load-displacement curves with compressive stiffness (7335 and 7079 N/mm), load (12,488 and 12,473 N), displacement (1.95 and 2.09 mm) and energy at failure (13.5 and 14.7 J) in agreement with experimental results (6551 ± 2017 N/mm, 12,411 ± 829 N, 2.1 ± 0.2 mm and 13.0 ± 1.5 J respectively). The fracture pattern and location also agreed with experimental results. The simulation performed with constants derived from quasi-static experiments showed a failure energy (13.2 J) and a fracture pattern and location in agreement with experimental results, but a compressive stiffness (1580 N/mm), a failure load (5976 N) and a displacement to failure (4.8 mm) outside the experimental corridors. The proposed method offers an innovative way to calibrate the hyperelastic material properties of the IVD and to offer a more realistic simulation of the FSU in fast dynamic compression.     

A two-layer elasto-visco-plastic rheological model for the material parameter identification of bone tissue

The ability to measure bone tissue material properties plays a major role in diagnosis of diseases and material modeling. Bone’s response to loading is complex and shows a viscous contribution to stiffness, yield and failure. It is also ductile and damaging and exhibits plastic hardening until failure. When performing mechanical tests on bone tissue, these constitutive effects are difficult to quantify, as only their combination is visible in resulting stress–strain data. In this study, a methodology for the identification of stiffness, damping, yield stress and hardening coefficients of bone from a single cyclic tensile test is proposed. The method is based on a two-layer elasto-visco-plastic rheological model that is capable of reproducing the specimens’ pre- and postyield response. The model’s structure enables for capturing the viscously induced increase in stiffness, yield, and ultimate stress and for a direct computation of the loss tangent. Material parameters are obtained in an inverse approach by optimizing the model response to fit the experimental data. The proposed approach is demonstrated by identifying material properties of individual bone trabeculae that were tested under wet conditions. The mechanical tests were conducted according to an already published methodology for tensile experiments on single trabeculae. As a result, long-term and instantaneous Young’s moduli were obtained, which were on average 3.64 GPa and 5.61 GPa, respectively. The found yield stress of 16.89 MPa was lower than previous studies suggest, while the loss tangent of 0.04 is in good agreement. In general, the two-layer model was able to reproduce the cyclic mechanical test data of single trabeculae with an root-mean-square error of 2.91 ± 1.77 MPa. The results show that inverse rheological modeling can be of great advantage when multiple constitutive contributions shall be quantified based on a single mechanical measurement.

     

Spherical indentation method for determining the constitutive parameters of hyperelastic soft materials

A comprehensive study on the spherical indentation of hyperelastic soft materials is carried out through combined theoretical, computational, and experimental efforts. Four widely used hyperelastic constitutive models are studied, including neo-Hookean, Mooney–Rivlin, Fung, and Arruda–Boyce models. Through dimensional analysis and finite element simulations, we establish the explicit relations between the indentation loads at given indentation depths and the constitutive parameters of materials. Based on the obtained results, the applicability of Hertzian solution to the measurement of the initial shear modulus of hyperelastic materials is examined. Furthermore, from the viewpoint of inverse problems, the possibility to measure some other properties of a hyperelastic material using spherical indentation tests, e.g., locking stretch, is addressed by considering the existence, uniqueness, and stability of the solution. Experiments have been performed on polydimethylsiloxane to validate the conclusions drawn from our theoretical analysis. The results reported in this study should help identify the extent to which the mechanical properties of hyperelastic materials could be measured from spherical indentation tests.     

Estimating material parameters of human skin in vivo

An accurate mathematical representation of the mechanical behaviour of human skin is essential when simulating deformations occurring in the skin during body movements or clinical procedures. In this study constitutive stress–strain relationships based on experimental data from human skin in vivo were obtained. A series of multiaxial loading experiments were performed on the forearms of four age- and gender matched subjects. The tissue geometry, together with recorded displacements and boundary forces, were combined in an analysis using finite element modelling. A non-linear optimization technique was developed to estimate values for the material parameters of a previously published constitutive law, describing the stress–strain relationship as a non-linear anisotropic membrane. Ten sets of material parameters where estimated from the experiments, showing considerable differences in mechanical behaviour both between individual subjects as well as mirrored body locations on a single subject. The accuracy of applications that simulate large deformations of human skin could be improved by using the parameters found from the in vivo experiments as described in this study.     

Purification of human brain tissue factor

Tissue factor (factor III) is a lipoprotein cofactor which markedly enhances the catalytic effect of coagulation factor VIIa upon factors IX and X. Human tissue factor apoprotein was purified 53,000-fold to homogeneity from brain using acetone delipidation, Triton X-100 extraction, and affinity chromatography upon factor VII-agarose. The purified apoprotein has an apparent molecular weight of 44,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an amino acid composition similar to bovine brain tissue factor, and an NH2-terminal amino acid sequence of Ser-X-Asn-Thr-Val-Ala-Val-Tyr-X-Tyr-X-Leu-Lys-(Ser)-Lys-Asn-Phe. Optimal relipidation of the tissue factor apoprotein was associated with a 5000-fold enhancement of clotting activity and occurred at a phospholipid/apoprotein (w/w) ratio of greater than 600.     

Magnetic analysis of human brain tissue

Fourteen samples of human hippocampal tissue were resected during amygdalo-hippocampectomies performed on patients suffering from Mesial Temporal Lobe Epilepsy (MTLE). In addition, eight tissue samples from the hippocampus, cortex basalganglia, cerebellum and leptomeninges were resected from cadavers during routine autopsy and were not chemically fixed. All samples were preserved in liquid nitrogen and magnetic properties were measured at 77K and 273K. Measurements indicate that there are no systematic variations in magnetic particle concentrations or magnetic properties between MTLE patients and non-pathologic tissue from the cadavers. The presence of superparamagnetic particles can be inferred due to differences in the saturation remanence acquired at 77K and 273K. This is a further indication that biogenic magnetite and/or maghemite present in the human brain likely is not primarily associated with geomagnetic field sensing as it is known to occur in other organisms     

A new antigen retrieval technique for human brain tissue

Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times.     

The collection and processing of human brain tissue for research

To further understand the neuroanatomy, neurochemistry and neuropathology of the normal and diseased human brain, it is essential to have access to human brain tissue where the biological and chemical nature of the tissue is optimally preserved. We have established a human brain bank where brain tissue is optimally processed and stored in order to provide a resource to facilitate neuroscience research of the human brain in health and disease. A donor programme has been established in consultation with the community to provide for the post-mortem donation of brain tissue to the brain bank. We are using this resource of human brain tissue to further investigate the basis of normal neuronal functioning in the human brain as well as the mechanisms of neuronal dysfunction and degeneration in neurodegenerative diseases. We have established a protocol for the preservation of post-mortem adult human brain tissue firstly by snap-freezing unfixed brain tissue and secondly by chemical fixation and then storage of this tissue at -80 degrees C in a human brain bank. Several research techniques such as receptor autoradiography, DNA and RNA analysis, are carried out on the unfixed tissue and immunohistochemical and histological analysis is carried out on the fixed human tissue. Comparison of tissue from normal control cases and from cases with neurodegenerative disorders is carried out in order to document the changes that occur in the brain in these disorders and to further investigate the underlying pathogenesis of these devastating neurological diseases.     

Cryopreservation of human brain tissue allowing timely production of viable adult human brain cells for autologous transplantation

BACKGROUND: Autologous transplantation is an attractive approach to treat some neurological diseases. A major obstacle is the capacity to produce cells for transplantation at the appropriate time. We describe a cryopreservation procedure for adult human brain tissue allowing the generation of cells in vitro. METHODS: Neurological resections were dissected to separate white and grey matter. Fractions were frozen in a specific cryopreservation medium containing a selected serum and stored in liquid nitrogen. Tissue was thawed, cells were mechanically dissociated, expanded in culture and characterized by immunochemistry. RESULTS: Adult human brain tissue cryopreserved for up to two years was successfully used to generate brain cells that could be maintained in culture for up to 100 days. Cells expressed a variety of neuroectodermal markers including GFAP, S100beta, and neurofilament. CONCLUSION: A successful procedure for cryopreservation of adult human brain tissue has been established that might facilitate future autologous transplantation strategies.     

Recent developments in the identification of human skeletal material

A review of publications over the last fifteen years of methods in the field of physical anthropology for aging and sexing human skeletal material is presented. The approaches used by various authors have been summarized into six categories: (1) Visual examination of bones (2) Anthropometric measurements of bones (3) Anthropometric measurements with subsequent use of statistics in the form of discriminate function analyses (4) Time and sequence of eruption of the teeth (5) x-ray examination of the internal structure of section bone (6) Microscopic examination of the internal structure of bone. A method to seasonally date prehistoric burials from the chitinous exuvia of fly pupae found with the burials is discussed.     

A general framework for the numerical implementation of anisotropic hyperelastic material models including non-local damage

The highly nonlinear mechanical behaviour of soft tissues solicited within the physiological range usually involves degradation of the material properties. Mechanically, having these biostructures undergoing such stretch patterns may bring about pathological conditions related to the steady deterioration of both collagen fibres and material’s ground substance. Tissue and subject variability observed in the phenomenological mechanical characterisation of soft tissues often hinder the choice of the computational constitutive model. Therefore, this contribution brings forth a detailed overview of the constitutive implementation in a computational framework of anisotropic hyperelastic materials with damage. Surmounting the challenge posed by the mesh dependency pathology requires the incorporation of an integral-type non-local averaging, which seeks to include the effects of the microstructure in order to limit the localisation phenomena of the damage variables. By adopting this approach, one can make use of multiple developed material models available in the literature, a combination of those, or even propose new models within the same numerical framework. The numerical examples of three-dimensional displacement and force-driven boundary value problems highlight the possibility of using multiple material models within the same numerical framework. Particularities concerning the considered material models and the damage effect implications to represent the Mullins effect, induced anisotropy, hysteresis, and mesh dependency are discussed.     

A panel of 11 region-specific radioimmunoassays for measurements of human chromogranin A

INTRODUCTION: The primary structure of human chromogranin A (CgA) not only contains 10 pairs of basic amino acids, which are potential cleavage sites for specific endogenous proteases, but also other sites in the molecule can be subjected to cleavage. Several CgA-related peptides have been identified in tissue, and many of the biological effects attributed to CgA seem to be mediated by these peptides. MATERIALS AND METHODS: Peptides homologous to defined parts of the human CgA molecule were selected and synthesised. Antibodies were raised, and 11 specific radioimmunoassays were developed. Plasma samples from 20 patients with neuroendocrine tumours were collected and measured in all assays. RESULTS: All assays measured circulating levels of CgA-derived peptides. Only four of the assays measured concentrations that correlated with that of total CgA. However, concentrations of the individual CgA-related peptides were generally lower than the concentration of total CgA. Different neuroendocrine tumours seem to process CgA differently. The ratio between a given region-specific assay and total CgA is inversely correlated to tumour activity. CONCLUSION: The assays presented allow measurements of defined regions of CgA and will thus become important tools for further studies of processing of CgA.