Inertia effects on characterization of dynamic response of brain tissue

Modeling and simulation of traumatic brain injury (TBI) resulted from collision or blast loading requires characterization of mechanical response over a wide range of loading rates under valid testing conditions. In this study, mechanical response of fresh bovine brain tissue was studied using the two modified Kolsky bar techniques. Radial deformation behavior of annular specimens, which are typically used to characterize the dynamic uniaxial compressive response of biological tissues, was examined using a modified Kolsky bar and a high speed camera to collect images while the specimen deforms at an axial strain rate of 2000s(-1). The high-speed images revealed inhomogeneous specimen deformation possibly brought about by radial inertia and causing a multi-axial stress state. To acquire valid stress-strain results that can be used to produce constitutive behavior of the soft materials, a novel torsion technique was developed to obtain pure shear response at dynamic loading rates. Experimental results show clear differences in the material response using the two methods. These results indicate that the previously demonstrated annular specimen geometry aimed at reducing inertia induced stress components for high rate soft materials uniaxial-compressive testing may still possess a significant component of radial inertia induced radial stress which consequently caused the observed inhomogeneous deformation in brain tissue test samples.     

A visco-hyperelastic-damage constitutive model for the analysis of the biomechanical response of the periodontal ligament

The periodontal ligament (PDL), as other soft biological tissues, shows a strongly non-linear and time-dependent mechanical response and can undergo large strains under physiological loads. Therefore, the characterization of the mechanical behavior of soft tissues entails the definition of constitutive models capable of accounting for geometric and material non-linearity. The microstructural arrangement determines specific anisotropic properties. A hyperelastic anisotropic formulation is adopted as the basis for the development of constitutive models for the PDL and properly arranged for investigating the viscous and damage phenomena as well to interpret significant aspects pertaining to ordinary and degenerative conditions. Visco-hyperelastic models are used to analyze the time-dependent mechanical response, while elasto-damage models account for the stiffness and strength decrease that can develop under significant loading or degenerative conditions. Experimental testing points out that damage response is affected by the strain rate associated with loading, showing a decrease in the damage limits as the strain rate increases. These phenomena can be investigated by means of a model capable of accounting for damage phenomena in relation to viscous effects. The visco-hyperelastic-damage model developed is defined on the basis of a Helmholtz free energy function depending on the strain-damage history. In particular, a specific damage criterion is formulated in order to evaluate the influence of the strain rate on damage. The model can be implemented in a general purpose finite element code. The accuracy of the formulation is evaluated by using results of experimental tests performed on animal model, accounting for different strain rates and for strain states capable of inducing damage phenomena. The comparison shows a good agreement between numerical results and experimental data.     

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

This paper deals with the mechanical characterization of brain tissue which behaves as a viscoelastic material. We focus on the linear viscoelastic behavior, which should apply for small strains at any strain rate, and demonstrate the applicability of the time/temperature superposition principle. This principle allows the opportunity to extend the range of shear rates for which the material is characterized, and makes the results applicable to impact conditions. This characterization of the linear behavior forms the basis for a further nonlinear characterization of the tissue.     

The influence of test conditions on characterization of the mechanical properties of brain tissue

To understand brain injuries better, the mechanical properties of brain tissue have been studied for 50 years; however, no universally accepted data set exists. The variation in material properties reported may be caused by differences in testing methods and protocols used. An overview of studies on the mechanical properties of brain tissue is given, focusing on testing methods. Moreover, the influence of important test conditions, such as temperature, anisotropy, and precompression was experimentally determined for shear deformation. The results measured at room temperature show a stiffer response than those measured at body temperature. By applying the time-temperature superposition, a horizontal shift factor a(T)=8.5-11 was found, which is in agreement with the values found in literature. Anisotropy of samples from the corona radiata was investigated by measuring the shear resistance for different directions in the sagittal, the coronal, and the transverse plane. The results measured in the coronal and the transverse plane were 1.3 and 1.25 times stiffer than the results obtained from the sagittal plane. The variation caused by anisotropy within the same plane of individual samples was found to range from 25% to 54%. The effect of precompression on shear results was investigated and was found to stiffen the sample response. Combinations of these and other factors (postmortem time, donor age, donor type, etc.) lead to large differences among different studies, depending on the different test conditions.     

Anisotropic constitutive equations and experimental tensile behavior of brain tissue

The present study deals with the experimental analysis and mechanical modeling of tensile behavior of brain soft tissue. A transversely isotropic hyperelastic model recently proposed by Meaney (2003) is adopted and mathematically studied under uniaxial loading conditions. Material parameter estimates are obtained through tensile tests on porcine brain materials accounting for regional and directional differences. Attention is focused on the short-term response. An extrapolation of tensile test data to the compression range is performed theoretically, to study the effect of the heterogeneity in the tensile/compressive response on the material parameters. Experimental and numerical results highlight the sensitivity of the adopted model to the test direction.     

Mechanical characterization of anisotropic planar biological soft tissues using large indentation: a computational feasibility study

Traditionally, the complex mechanical behavior of planar soft biological tissues is characterized by (multi)axial tensile testing. While uniaxial tests do not provide sufficient information for a full characterization of the material anisotropy, biaxial tensile tests are difficult to perform and tethering effects limit the analyses to a small central portion of the test sample. In both cases, determination of local mechanical properties is not trivial. Local mechanical characterization may be performed by indentation testing. Conventional indentation tests, however, often assume linear elastic and isotropic material properties, and therefore these tests are of limited use in characterizing the nonlinear, anisotropic material behavior typical for planar soft biological tissues. In this study, a spherical indentation experiment assuming large deformations is proposed. A finite element model of the aortic valve leaflet demonstrates that combining force and deformation gradient data, one single indentation test provides sufficient information to characterize the local material behavior. Parameter estimation is used to fit the computational model to simulated experimental data. The aortic valve leaflet is chosen as a typical example. However, the proposed method is expected to apply for the mechanical characterization of planar soft biological materials in general.     

Environmentally-controlled Microtensile Testing of Mechanically-adaptive Polymer Nanocomposites for ex vivo Characterization

Implantable microdevices are gaining significant attention for several biomedical applications^1-4. Such devices have been made from a range of materials, each offering its own advantages and shortcomings^5,6. Most prominently, due to the microscale device dimensions, a high modulus is required to facilitate implantation into living tissue. Conversely, the stiffness of the device should match the surrounding tissue to minimize induced local strain^7-9. Therefore, we recently developed a new class of bio-inspired materials to meet these requirements by responding to environmental stimuli with a change in mechanical properties^10-14. Specifically, our poly(vinyl acetate)-based nanocomposite (PVAc-NC) displays a reduction in stiffness when exposed to water and elevated temperatures (e.g. body temperature). Unfortunately, few methods exist to quantify the stiffness of materials in vivo¹⁵, and mechanical testing outside of the physiological environment often requires large samples inappropriate for implantation. Further, stimuli-responsive materials may quickly recover their initial stiffness after explantation. Therefore, we have developed a method by which the mechanical properties of implanted microsamples can be measured ex vivo, with simulated physiological conditions maintained using moisture and temperature control^13,16,17.To this end, a custom microtensile tester was designed to accommodate microscale samples^13,17 with widely-varying Young''s moduli (range of 10 MPa to 5 GPa). As our interests are in the application of PVAc-NC as a biologically-adaptable neural probe substrate, a tool capable of mechanical characterization of samples at the microscale was necessary. This tool was adapted to provide humidity and temperature control, which minimized sample drying and cooling¹⁷. As a result, the mechanical characteristics of the explanted sample closely reflect those of the sample just prior to explantation.The overall goal of this method is to quantitatively assess the in vivo mechanical properties, specifically the Young''s modulus, of stimuli-responsive, mechanically-adaptive polymer-based materials. This is accomplished by first establishing the environmental conditions that will minimize a change in sample mechanical properties after explantation without contributing to a reduction in stiffness independent of that resulting from implantation. Samples are then prepared for implantation, handling, and testing (Figure 1A). Each sample is implanted into the cerebral cortex of rats, which is represented here as an explanted rat brain, for a specified duration (Figure 1B). At this point, the sample is explanted and immediately loaded into the microtensile tester, and then subjected to tensile testing (Figure 1C). Subsequent data analysis provides insight into the mechanical behavior of these innovative materials in the environment of the cerebral cortex.     

Inverse identification of region-specific hyperelastic material parameters for human brain tissue

The identification of material parameters accurately describing the region-dependent mechanical behavior of human brain tissue is crucial for computational models used to assist, e.g., the development of safety equipment like helmets or the planning and execution of brain surgery. While the division of the human brain into different anatomical regions is well established, knowledge about regions with distinct mechanical properties remains limited. Here, we establish an inverse parameter identification scheme using a hyperelastic Ogden model and experimental data from multi-modal testing of tissue from 19 anatomical human brain regions to identify mechanically distinct regions and provide the corresponding material parameters. We assign the 19 anatomical regions to nine governing regions based on similar parameters and microstructures. Statistical analyses confirm differences between the regions and indicate that at least the corpus callosum and the corona radiata should be assigned different material parameters in computational models of the human brain. We provide a total of four parameter sets based on the two initial Poisson’s ratios of 0.45 and 0.49 as well as the pre- and unconditioned experimental responses, respectively. Our results highlight the close interrelation between the Poisson’s ratio and the remaining model parameters. The identified parameters will contribute to more precise computational models enabling spatially resolved predictions of the stress and strain states in human brains under complex mechanical loading conditions.

     

Dynamic mechanical response of bovine gray matter and white matter brain tissues under compression

Dynamic responses of brain tissues are needed for predicting traumatic brain injury (TBI). We modified a dynamic experimental technique for characterizing high strain-rate mechanical behavior of brain tissues. Using the setup, the gray and white matters from bovine brains were characterized under compression to large strains at five different strain rates ranging from 0.01 to 3000/s. The white matter was examined both along and perpendicular to the coronal section for anisotropy characterization. The results show that both brain tissue matters are highly strain-rate sensitive. Differences between the white matter and gray matter in their mechanical responses are recorded. The white matter shows insignificant anisotropy over all strain rates. These results will lead to rate-dependent material modeling for dynamic event simulations.     

A novel experimental method to estimate stress-strain behavior of intact coronary arteries using intravascular ultrasound (IVUS)

Most arterial mechanics studies have focused on excised non-coronary vessels, with few studies validating the application of ex-vivo results to in-vivo conditions. A method was developed for testing the mechanical properties of intact left anterior descending coronary arteries under a variety of conditions. Vascular deformation and pressure were simultaneously measured with intravascular ultrasound and a pressure transducer guidewire, respectively. Results suggest the importance of understanding in-vivo factors such as myocardial support, vascular tone and local pressure fluctuations when applying ex-vivo coronary characterization data. With further development, this method can more accurately characterize the true in-vivo constitutive behavior in normal and atherosclerotic coronaries.     

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 Testing Platform for Durability Studies of Polymers and Fiber-reinforced Polymer Composites under Concurrent Hygrothermo-mechanical Stimuli

The durability of polymers and fiber-reinforced polymer composites under service condition is a critical aspect to be addressed for their robust designs and condition-based maintenance. These materials are adopted in a wide range of engineering applications, from aircraft and ship structures, to bridges, wind turbine blades, biomaterials and biomedical implants. Polymers are viscoelastic materials, and their response may be highly nonlinear and thus make it challenging to predict and monitor their in-service performance. The laboratory-scale testing platform presented herein assists the investigation of the influence of concurrent mechanical loadings and environmental conditions on these materials. The platform was designed to be low-cost and user-friendly. Its chemically resistant materials make the platform adaptable to studies of chemical degradation due to in-service exposure to fluids. An example of experiment was conducted at RT on closed-cell polyurethane foam samples loaded with a weight corresponding to ~50% of their ultimate static and dry load. Results show that the testing apparatus is appropriate for these studies. Results also highlight the larger vulnerability of the polymer under concurrent loading, based on the higher mid-point displacements and lower residual failure loads. Recommendations are made for additional improvements to the testing apparatus.     

Effects of boundary conditions on the estimation of the planar biaxial mechanical properties of soft tissues

Evaluation and simulation of the multiaxial mechanical behavior of native and engineered soft tissues is becoming more prevalent. In spite of this growing use, testing methods have not been standardized and methodologies vary widely. The strong influence of boundary conditions were recently underscored by Waldman et al. [2002, J. Materials Science: Materials in Medicine 13, pp. 933-938] wherein substantially different experimental results were obtained using different sample gripping methods on the same specimens. As it is not possible to experimentally evaluate the effects of different biaxial test boundary conditions on specimen internal stress distributions, we conducted numerical simulations to explore these effects. A nonlinear Fung-elastic constitutive model (Sun et al., 2003, JBME 125, pp. 372-380, which fully incorporated the effects of in-plane shear, was used to simulate soft tissue mechanical behavior. Effects of boundary conditions, including varying the number of suture attachments, different gripping methods, specimen shapes, and material axes orientations were examined. Results demonstrated strong boundary effects with the clamped methods, while suture attachment methods demonstrated minimal boundary effects. Suture-based methods appeared to be best suited for biaxial mechanical tests of biological materials. Moreover, the simulations demonstrated that Saint-Venant's effects depended significantly on the material axes orientation. While not exhaustive, these comprehensive simulations provide experimentalists with additional insight into the stress-strain fields associated with different biaxial testing boundary conditions, and may be used as a rational basis for the design of biaxial testing experiments.     

Towards a reliable characterisation of the mechanical behaviour of brain tissue: The effects of post-mortem time and sample preparation

Since the early seventies, the material properties of brain tissue have been studied using a variety of testing techniques. However, data reported in literature show large discrepancies even in the linear viscoelastic regime. In the current study, the effect of the sample preparation procedure and of post-mortem time on the mechanical response of porcine brain tissue is examined. Samples from the thalamus region were prepared with different techniques and were tested for different loading histories. Each sample was tested in oscillatory shear tests (1% strain amplitude, 1-10 Hz frequencies) followed by sequences of 5% strain loading-unloading cycles. The stress response to the loading-unloading cycles showed a clear dependency on post-mortem time, becoming more stiff with increasing time. This dependency was affected by the mechanical history induced by the preparation procedure.     

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

During growth and development, the immature central nervous system undergoes rapid alterations in constituents and structure. We hypothesize that these alterations are accompanied by changes in the mechanical properties of brain tissue which, in turn, influence the response of the brain to traumatic inertial loads. Samples of frontal cerebrum from neonatal (2–3 days) and adult pigs were harvested and tested within 3 h post-mortem. The complex shear modulus of the samples was measured in a custom-designed oscillatory shear testing device at engineering shear strain amplitudes of 2.5% or 5% from 20–200 Hz, at 25°C and 100% humidity. In this range, the elastic and viscous components of the complex shear modulus increased significantly with the development of the cerebral region of the brain. Using an idealized model of the developing head, the age-dependent material properties of brain tissue were shown to affect the mechanical response of the brain to inertial loading. This study is a first step toward developing head injury tolerance criteria specifically for the pediatric population.     

Anomalous rate dependence of the preconditioned response of soft tissue during load controlled deformation

It has been observed in load controlled laboratory tests of myocardium and skin that the tissues can exhibit a decrease in nonlinear stiffness with an increase in loading rate: the faster a test is performed, the more compliant is the preconditioned material behavior. This response seems to conflict with what is generally expected of soft tissues based on stretch or strain controlled tests, in which an increased rate of deformation results in a stiffer material response. It is hypothesized that this anomalous behavior has not been observed previously due to the small number of cyclic load controlled mechanical characterization tests that are geared specifically towards viscoelastic tissue response. The goal of this paper is to examine the preconditioned response of soft tissue to load controlled deformation using nonlinear viscoelastic material models including quasi-linear viscoelasticity, and to determine under what conditions this anomalous behavior becomes apparent. Results from this study suggest that this behavior is a true phenomenon unique to load controlled deformations that results from the interplay of nonlinear effects and creep behavior. These results call for increased attention to experimental parameters when testing and modeling nonlinear viscoelastic material behavior.     

Are in vivo and in situ brain tissues mechanically similar?

Brain tissue mechanical properties have been well-characterized in vitro, and were found to be inhomogeneous, nonlinear anisotropic and influenced by neurological development and postmortem time interval prior to testing. However, brain in vivo is a vascularized tissue, and there is a paucity of information regarding the effect of perfusion on brain mechanical properties. Furthermore, mechanical properties are often extracted from preconditioned tissue, and it remains unclear if these properties are representative of non-preconditioned tissue. We present non-preconditioned (NPC) and preconditioned (PC) relaxation responses of porcine brain (N = 10) obtained in vivo, in situ and in vitro, at anterior, mid and posterior regions of the cerebral cortex during 4mm indentations at either 3 or 1 mm/s. Material property characteristics showed no dependency on the site tested, thus revealing that cortical gray matter on the parietal and frontal lobes can be considered homogenous. In most cases, preconditioning decreased the shear moduli, with a more pronounced effect in the dead (in situ and in vitro) brain. For most conditions, it was found that only the long-term time constant of relaxation (tau > 20 s) significantly decreased from in vivo to in situ modes (p < 0.02), and perfusion had no effect on any other property. These findings support the concept that perfusion does not affect the stiffness of living cortical tissue.     

一种新型椎体后凸成型术重建胸腰椎骨折椎体的基础研究

目的:评估一种一种新型椎体后凸成型术的临床操作可行性及力学测试。方法:将16个新鲜椎体标本(T12-L3)随机分为2组,模拟临床手术操作进行椎体强化,一组采用新型椎体后凸成型术,另一组采用传统注射式椎体成型术,并对强化后的椎体进行力学测试,观察骨水泥的渗漏率、强化后伤椎的强度和刚度。结果:新型椎体后凸成型术组没有出现骨水泥渗漏,传统注射式椎体成型术组有2例出现骨水泥渗漏。新型椎体后凸成型术组术后伤椎的强度和刚度分别为(3457.4±653.7)N和(787.5±283.6)N/mm,传统注射式椎体成型术后伤椎的强度和刚度分别为(2584.2±414.3)N和(524.4±157.4)N/mm,新型椎体后凸成型术术后伤椎强度和刚度的恢复明显优于传统注射式椎体成型术。结论:采用新型囊袋状的扩张器行椎体后凸成型术可以明显降低骨水泥的渗漏率,可以明显恢复伤椎的强度和刚度,新型囊袋状式椎体后凸成型术是治疗胸腰椎骨折一种有效方法。     

The effect of microwaves on the bioelectric brain activity

The experiments on rats have shown that the effect of millimeter range electromagnetic radiation on the bioelectric brain activity is dependent on the initial functional state of central nervous system. Microwaves are able to cause a nonspecific electroencephalographic reaction of synchronization and probably the lower the bioelectric brain process dynamics of active rats. Enrichment of electrocorticograms with high-frequency rhythms and increase in degree of bioelectric brain dynamics can be observed in narcosis conditions. The appearance of biological resonance in the brain of narcotized rats preliminary injected aminazin by pulse-modulated microwaves is noted. This is expressed as epileptiform convulsive activity in electrocorticogram. It has been shown that the nonlinear dynamics method may provide a reliable characterization of changing bioelectric brain activity under of nonionized electromagnetic fields. It is possible to modulate the bioelectric brain activity by microwaves to change the functional state of central nervous system and probably of the whole organism.     

Intracranial Stereotaxic Cannulation for Development of Orthotopic Glioblastoma Allograft in Sprague-Dawley Rats and Histoimmunopathological Characterization of the Brain Tumor

Glioblastoma is the most common brain tumor that causes significant mortality annually. Limitations of the current therapeutic regimens warrant development of new techniques and treatment strategies in orthotopic animal model for better management of this devastating brain cancer. There are only a few experimental orthotopic models of glioblastoma for pre-clinical testing. In the present investigation, we successfully implanted rat C6 cells via intracranial stereotaxic cannulation in adult Sprague-Dawley rats for development and histoimmunopathological characterization of an advanced orthotopic glioblastoma allograft model, which could be useful for investigating the course of glioblastoma development as well as for testing efficacy of new therapeutic agents. The orthotopic glioblastoma allograft was generated by intracerebral injection of rat C6 cells through a guide-cannula system and after 21 post-inoculation days the brain tumor was characterized by histoimmunopathological experiments. Histological staining and immunofluorescent labelings for TERT, VEGF, Bcl-2, survivin, XIAP, and GFAP revealed the distinct characteristics of glioblastoma in C6 allograft, which could be useful as a target for treatment with emerging new therapeutic agents. Our investigation indicated the successful development of intracranial cannulated orthotopic glioblastoma allograft in adult Sprague-Dawley rats, making it as a useful animal model of glioblastoma for pre-clinical evaluation of various therapeutic strategies for the management of glioblastoma. Special issue in honor of Naren Banik.