Modelling the Brain for Rotational Loading: Shear Effects and Other Complications

This study considers modelling the brain due to rotation of the skull where, at lower frequencies, the shear property of the material is important. Investigations reported here cover the effect of elastic and viscoelastic (lossy) cerebral material, the effect of the Falx protruding into the brain, the gap around the Falx and the brain filled with non viscous fluid in addition to different models of the Falx with bending or membrane stiffness. Analytical benchmark formulations are also described for the simple 2D plane strain in a cylinder produced by a half-sine rotation on the outer periphery which allows numerical (Finite Element) models to be validated. The results show the importance of the material properties, duration of loading and amplitude of loading as well as the influence of the partition. The results are shown for predicted maximum Principal strains in the models, as this may well be indicative of whether damage of the brain tissue occurs.     

Proposing a Radial Basis Function and CSDM Indices to Predict the Traumatic Brain Injury Risk

BackgroundMany head injury indices and finite element (FE) head models have been proposed to predict traumatic brain injury (TBI). Although FE head models are suitable methods with high accuracy, they are computationally intensive. Head motion-based brain injury criteria are usually fast tools with lower accuracy. So, the objective of this study is to propose new criteria along with an artificial neural network model to predict TBI risks, which can be fast and accurate.MethodsFor this purpose, 250 FE head simulations have been carried out at 5 magnitudes and 50 rotational impact directions using the SIMon model. The effects of directions and magnitudes of rotational impacts were assessed for cumulative strain damage measure (CSDM) values. Next, statistical analysis and neural network were applied to predict CSDM values.ResultsThe results of the present research showed that the direction of rotation in the sagittal and frontal planes had a considerable effect on the CSDM values. Furthermore, new brain injury indices and a radial basis function neural network have been proposed to predict CSDM values which having high correlation coefficients with SIMon responses.ConclusionsThe results of this research demonstrated that rotational impact directions should be used to develop new head injury criteria being able to predict CSDM values. However, findings of present research proved that head motion-based brain injury criteria and RBF network can be used to predict FE head model responses with high speed and accuracy.     

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.

     

Constitutive modelling of brain tissue: Experiment and theory

Recent developments in computer-integrated and robot-aided surgery—in particular, the emergence of automatic surgical tools and robots—as well as advances in virtual reality techniques, call for closer examination of the mechanical properties of very soft tissues (such as brain, liver, kidney, etc.). The ultimate goal of our research into the biomechanics of these tissues is the development of corresponding, realistic mathematical models. This paper contains experimental results of in vitro, uniaxial, unconfined compression of swine brain tissue and discusses a single-phase, non-linear, viscoelastic tissue model. The experimental results obtained for three loading velocities, ranging over five orders of magnitude, are presented. The applied strain rates have been much lower than those applied in previous studies, focused on injury modelling. The stress-strain curves are concave upward for all compression rates containing no linear portion from which a meaningful elastic modulus might be determined. The tissue response stiffened as the loading speed increased, indicating a strong stress-strain rate dependence. The use of the single-phase model is recommended for applications in registration, surgical operation planning and training systems as well as a control system of an image-guided surgical robot. The material constants for the brain tissue are evaluated. Agreement between the proposed theoretical model and experiment is good for compression levels reaching 30% and for loading velocities varying over five orders of magnitude.     

pH敏感纳米粒的制备和功能表征

目的:制备具有pH响应的甲氧基聚乙二醇甲基丙烯酸-2-六亚甲基亚胺乙酯聚合物,测试材料pH功能响应,以及建立聚合物纳米粒载药方法。方法:通过核磁共振氢谱鉴定ATRP(Atom Transfer Radical Polymerization)聚合反应所获得的化合物结构。滴加-搅拌挥发法制备聚乙二醇甲基丙烯酸-2-六亚甲基亚胺乙酯纳米粒,酶标仪测定其载药量和包封率。透射电镜下观察其形态,激光粒度仪分析测定其粒径,包载DiR红外荧光探针检测纳米粒pH响应功能。结果:分别成功合成得到2-溴代异丁酸聚乙二醇单甲醚和甲基丙烯酸-2-六亚甲基亚胺乙酯单体。通过ATRP聚合反应成功合成聚乙二醇甲基丙烯酸-2-六亚甲基亚胺乙酯聚合物材料,并通过核磁氢谱对聚合材料进行鉴定。通过滴加搅拌法制备包载有模型药物香豆素-6的纳米粒,并对纳米粒的形态表征及载药量进行测定。结论:试验结果表明制备得到的聚合物纳米粒尺寸均匀,具有预期的pH响应效果,可以装载模型药物。     

On the Effects of Cyclic Transversal Forces on Osseointegrated Dental Implants: Experimental and Finite Element Shakedown Analyses

This paper is concerned with the mechanical strength of fixed osseointegrated dental implants subjected to cyclic external loads, applied mainly in a direction orthogonal to their axis. Such a loading condition, seen as a basic design action for the implant, has been given little attention so far. Experimental results and numerical simulations, performed on two- and three-dimensional Finite Element models, are discussed. The shakedown theory is used to show that a common implant design (threaded fixture-abutment-connection screw) is susceptible of low-cycle fatigue failure under loading conditions well within the working range, even if the same design is able to withstand loading of the same type, but applied monotonically, much in excess of the working values. The shakedown analyses give an indication of several possible failure modalities: the low-cycle fatigue either of the implant or of the connection screw, or the loosening of the connection screw itself. Experimental and numerical results are in good qualitative agreement, and both suggest that the issue of transversal cyclic loading on fixed dental implants should be carefully reconsidered in the design phase.     

The effect of scatter correction and radius of rotation on semiquantitative measurements in SPECT 123I-FP-CIT imaging. A phantom study

PurposeThe high energy emissions of ¹²³I and the suboptimal radius of rotation affect the semiquantitative measurements performed during ¹²³I-FP-CIT tomographic imaging. An in-house extra low cost striatum phantom with brain and striatum compartments was constructed and was used to study the effects of Triple Energy Window scatter correction (TEW-SC) and radius of rotation on the Specific Binding Ratio (SBR) measurements.Materials and methodsThe phantom compartments were filled with radioactive ¹²³I solutions with varying concentrations, in a series of experiments. Tomographic images were acquired at six different radii of rotation, with and without TEW-SC and the SBRs were calculated using appropriate regions of interest, as in clinical imaging.ResultsSBRs decreased with increasing radius of rotation in both non-SC and TEW-SC images, the decrease being more pronounced in the latter. The application of TEW-SC increases SBR values by 40% on average. A maximum %Recovery of 42.7% of the true SBR value was achieved in the non-SC images, which increased to 64.6% after TEW-SC. Appropriate correction factors (CF) were calculated in order to make the SBR values independent on the radius of rotation, which could be used to correct SBR values obtained from tomographic acquisitions with suboptimal radius of rotation.ConclusionThe use of appropriate CF can provide more consistent SBR values and a more meaningful comparison between SBRs calculated from images acquired at different radii of rotation.     

A mechanistic damage model for ligaments

PurposeThe accuracy of biomechanical models is predicated on the realism by which they represent their biomechanical tissues. Unfortunately, most models use phenomenological ligament models that neglect the behaviour in the failure region. Therefore, the purpose of this investigation was to test whether a mechanistic model of ligamentous tissue portrays behaviour representative of actual ligament failure tests.ModelThe model tracks the time-evolution of a population of collagen fibres in a theoretical ligament. Each collagen fibre is treated as an independent linear cables with constant stiffness. Model equations were derived by assuming these fibres act as a continuum and applying a conservation law akin to Huxley’s muscle model. A breaking function models the rate of collagen fibre breakage at a given displacement, and was chosen to be a linear function for this preliminary analysis.MethodsThe model was fitted to experimental average curves for the cervical anterior longitudinal ligament. In addition, the model was cyclically loaded to test whether the tissue model behaves similarly.ResultsThe model agreed very well with experiment with an RMS error of 14.23 N and an R² of 0.995. Cyclic loading exhibited a reduction in force similar to experimental data.Discussion and conclusionThe proposed model showcases behaviour reminiscent of actual ligaments being strained to failure and undergoing cyclic load. Future work could incorporate viscous effects, or validate the model further by testing it in various loading conditions. Characterizing the breaking function more accurately would also lead to better results.     

Methyleugenol reduces cerebral ischemic injury by suppression of oxidative injury and inflammation

Abstract

The present study tested the cytoprotective effect of methyleugenol in an in vivo ischemia model (i.e. middle cerebral artery occlusion (MCAO) for 1.5 h and subsequent reperfusion for 24 h) and further investigated its mechanism of action in in vitro cerebral ischemic models. When applied shortly after reperfusion, methyleugenol largely reduced cerebral ischemic injury. Methyleugenol decreased the caspase-3 activation and death of cultured cerebral cortical neurons caused by oxygen-glucose deprivation (OGD) for 1 h and subsequent re-oxygenation for 24 h. Methyleugenol markedly reduced superoxide generation in the ischemic brain and decreased the intracellular oxidative stress caused by OGD/re-oxygenation. It was found that methyleugenol elevated the activities of superoxide dismutase and catalase. Further, methyleugenol inhibited the production of nitric oxide and decreased the protein expression of inducible nitric oxide synthase. Methyleugenol down-regulated the production of pro-inflammatory cytokines in the ischemic brain as well as in immunostimulated mixed glial cells. The results indicate that methyleugenol could be useful for the treatment of ischemia/inflammation-related diseases.     

Mechanical properties of brain tissue in tension

This paper contains experimental results of in vitro, uniaxial tension of swine brain tissue in finite deformation as well as proposes a new hyper-viscoelastic constitutive model for the brain tissue. The experimental results obtained for two loading velocities, corresponding to strain rates of 0.64 and 0.64 x 10(-2)s(-1), are presented. We believe that these are the first ever experiments of this kind. The applied strain rates were similar to those applied in our previous study, focused on explaining brain tissue properties in compression. The stress-strain curves are convex downward for all extension rates. The tissue response stiffened as the loading speed increased, indicating a strong stress-strain rate dependence. Swine brain tissue was found to be considerably softer in extension than in compression. Previously proposed in the literature brain tissue constitutive models, developed based on experimental data collected in compression are shown to be inadequate to explain tissue behaviour in tension. A new, non-linear, viscoelastic model based on the generalisation of the Ogden strain energy hyper-elastic constitutive equation is proposed. The new model accounts well for brain tissue deformation behaviour in both tension and compression (natural strain in <-0.3,0.2>) for strain rates ranging over five orders of magnitude.     

Fatigue Loading Effect in Custom-Made All-on-4 Implants System: A 3D Finite Elements Analysis

ObjectivesThis study aims to evaluate the fatigue stress around custom-made all-on-4 implants system to find out which type of implants have a better performance under different graded multidirectional occlusal forces.Material and methods3D normal and implanted models simulating the “All-on-4” concept were created and analyzed under three different conditions of occlusal loadings. Two types of static and fatigue were applied. Stress distribution was analyzed based on von Mises and Goodman theories in ANSYS environment in addition to the safety factor. Statistical tests were performed to assess the significance of the results as well as the reproducibility of the results.ResultsThe results showed stress increasing reaching a value of 48%, 29% in tilted implants compared to vertical implants and normal cases respectively. In contrast, tilted implants appeared to be less stable (safety factor may reach 0.7) and they may fail during the application of occlusal forces. The safety factor of cortical bone decreased by about 91% in the implanted model compared to the normal model, indicating a higher possibility of bone remodeling around the bone.ConclusionThe orientation and position of occlusal forces had an important influence on stress distribution between the implant and the surrounding bone, and fatigue loading caused greater stresses in comparison with static loading. Lower amounts of stress were found in the vertical implants, ensuring a higher safety factor and a longer clinical service. In contrast, the critical safety factor values are observed in tilted implants, which may fail under the influence of applied occlusal forces.     

Monte Carlo simulation of eye lens dose reduction from CT scan using organ based tube current modulation

PurposeTo investigate lens dose reduction with organ based tube current modulation (TCM) using the Monte Carlo method.MethodsTo calculate lens dose with organ based TCM, 36 pairs of X-ray sources with bowtie filters were placed around the patient head using a projection angle interval of 10° for one rotation of Computed Tomography (CT). Each projection was simulated respectively. Both voxelized and stylized eye models and Chinese reference male phantoms were used in the simulation, and tube voltages 80, 100, 120 and 140 kVp were used.ResultsDose differences between two eye models were less than 20%, but large variations were observed among dose results from different projections of all tube voltages investigated. Dose results from 0° (AP) directions were 60 times greater than those from 180° (PA) directions, which enables organ based TCM reduce lens doses by more than 47%.ConclusionsOrgan based TCM may be used to reduce lens doses. Stylized eye models are more anatomically realistic compared with voxelized eye models and are more reliable for dose evaluation.     

Influence of Head Motion on the Accuracy of 3D Reconstruction with Cone-Beam CT: Landmark Identification Errors in Maxillofacial Surface Model

PurposeThe purpose of this study was to investigate the influence of head motion on the accuracy of three-dimensional (3D) reconstruction with cone-beam computed tomography (CBCT) scan.ResultsRendered surface models with head motion were similar to the control model in appearance; however, the landmark identification errors showed larger values in models with head motion than in the control. In particular, the Porion in the horizontal rotation models presented statistically significant differences (P < .05). Statistically significant difference in the errors between the right and left side landmark was present in the left side rotation which was opposite direction to the scanner rotation (P < .05).ConclusionsPatient movement during CBCT scan might cause landmark identification errors on the 3D surface model in relation to the direction of the scanner rotation. Clinicians should take this into consideration to prevent patient movement during CBCT scan, particularly horizontal movement.     

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.     

Quantifying dynamic mechanical properties of human placenta tissue using optimization techniques with specimen-specific finite-element models

Motor-vehicle crashes are the leading cause of fetal deaths resulting from maternal trauma in the United States, and placental abruption is the most common cause of these deaths. To minimize this injury, new assessment tools, such as crash-test dummies and computational models of pregnant women, are needed to evaluate vehicle restraint systems with respect to reducing the risk of placental abruption. Developing these models requires accurate material properties for tissues in the pregnant abdomen under dynamic loading conditions that can occur in crashes. A method has been developed for determining dynamic material properties of human soft tissues that combines results from uniaxial tensile tests, specimen-specific finite-element models based on laser scans that accurately capture non-uniform tissue-specimen geometry, and optimization techniques. The current study applies this method to characterizing material properties of placental tissue. For 21 placenta specimens tested at a strain rate of 12/s, the mean failure strain is 0.472±0.097 and the mean failure stress is 34.80±12.62 kPa. A first-order Ogden material model with ground-state shear modulus (μ) of 23.97±5.52 kPa and exponent (α₁) of 3.66±1.90 best fits the test results. The new method provides a nearly 40% error reduction (p<0.001) compared to traditional curve-fitting methods by considering detailed specimen geometry, loading conditions, and dynamic effects from high-speed loading. The proposed method can be applied to determine mechanical properties of other soft biological tissues.     

An anatomically detailed and personalizable head injury model: Significance of brain and white matter tract morphological variability on strain

Finite element head (FE) models are important numerical tools to study head injuries and develop protection systems. The generation of anatomically accurate and subject-specific head models with conforming hexahedral meshes remains a significant challenge. The focus of this study is to present two developmental works: first, an anatomically detailed FE head model with conforming hexahedral meshes that has smooth interfaces between the brain and the cerebrospinal fluid, embedded with white matter (WM) fiber tracts; second, a morphing approach for subject-specific head model generation via a new hierarchical image registration pipeline integrating Demons and Dramms deformable registration algorithms. The performance of the head model is evaluated by comparing model predictions with experimental data of brain–skull relative motion, brain strain, and intracranial pressure. To demonstrate the applicability of the head model and the pipeline, six subject-specific head models of largely varying intracranial volume and shape are generated, incorporated with subject-specific WM fiber tracts. DICE similarity coefficients for cranial, brain mask, local brain regions, and lateral ventricles are calculated to evaluate personalization accuracy, demonstrating the efficiency of the pipeline in generating detailed subject-specific head models achieving satisfactory element quality without further mesh repairing. The six head models are then subjected to the same concussive loading to study the sensitivity of brain strain to inter-subject variability of the brain and WM fiber morphology. The simulation results show significant differences in maximum principal strain and axonal strain in local brain regions (one-way ANOVA test, p < 0.001), as well as their locations also vary among the subjects, demonstrating the need to further investigate the significance of subject-specific models. The techniques developed in this study may contribute to better evaluation of individual brain injury and the development of individualized head protection systems in the future. This study also contains general aspects the research community may find useful: on the use of experimental brain strain close to or at injury level for head model validation; the hierarchical image registration pipeline can be used to morph other head models, such as smoothed-voxel models.

     

Large brain size is associated with low extra‐pair paternity across bird species

BackgroundGaining extrapair copulations (EPCs) is a complicated behavior process. The interaction between males and females to procure EPCs may be involved in brain function evolution and lead to a larger brain. Thus, we hypothesized that extrapair paternity (EPP) rate can be predicted by relative brain size in birds. Past work has implied that the EPP rate is associated with brain size, but empirical evidence is rare.MethodsWe collated data from published references on EPP levels and brain size of 215 bird species to examine whether the evolution of EPP rate can be predicted by brain size using phylogenetically generalized least square (PGLS) models and phylogenetic path analyses.ResultsWe found that EPP rates (both the percentage EP offspring and percentage of broods with EP offspring) are negatively associated with relative brain size. We applied phylogenetic path analysis to test the causal relationship between relative brain size and EPP rate. Best‐supported models (ΔCICc < 2) suggested that large brain lead to reduced EPP rate, which failed to support the hypothesis that high rates of EPP cause the evolution of larger brains.ConclusionThis study indicates that pursuing EPCs may be a natural instinct in birds and the interaction between males and females for EPCs may lead to large brains, which in turn may restrict their EPC level for both sexes across bird species.     

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies.     

Bayesian inference for parameter estimation in lactoferrin-mediated iron transport across blood-brain barrier

BackgroundIn neurodegenerative diseases such as Alzheimer's and Parkinson's, excessive irons as well as lactoferrin (Lf), but not transferrin (Tf), have been found in and around the affected regions of the brain. These evidences suggest that lactoferrin plays a critical role during neurodegenerative diseases, although Lf-mediated iron transport across blood-brain barrier (BBB) is negligible compared to that of transferrin in normal condition. However, the kinetics of lactoferrins and lactoferrin-mediated iron transport are still unknown.MethodTo determine the kinetic rate constants of lactoferrin-mediated iron transport through BBB, a mass-action based ordinary differential equation model has been presented. A Bayesian framework is developed to estimate the kinetic rate parameters from posterior probability density functions. The iron transport across BBB is studied by considering both Lf- and Tf-mediated pathways for both normal and pathologic conditions.ResultsUsing the point estimates of kinetic parameters, our model can effectively reproduce the experimental data of iron transport through BBB endothelial cells. The robustness of the model and parameter estimation process are further verified by perturbation of kinetic parameters. Our results show that surge in high-affinity receptor density increases lactoferrin as well as iron in the brain.ConclusionsDue to the lack of a feedback loop such as iron regulatory proteins (IRPs) for lactoferrin, iron can transport to the brain continuously, which might increase brain iron to pathological levels and can contribute to neurodegeneration.General significanceThis study provides an improved understanding of presence of lactoferrin and iron in the brain during neurodegenerative diseases.     

Hyperphagia in offsprings of in utero hyperglycemic mothers is associated with increased expression of heparan sulfate proteoglycans in hypothalamus

In utero hyperglycemia has consequences on future outcomes in the offsprings. We had earlier shown that in utero hyperglycemia impacts proteoglycans/glycosaminoglycans, one of the key molecules involved in brain development. Hypothalamic HSPGs such as syndecan-1 and syndecan-3 are well known for their involvement in feeding behavior. Therefore, studies were carried out to determine the effect of maternal hyperglycemia on the expression of HSPGs in the hypothalamus of offspring brain. Results revealed increased protein abundance of Syndecan-1 and -3 as well as glypican-1 in postnatal adults from hyperglycemic mothers. This was associated with increased hyperphagia and increased expression of Neuropeptide Y. These results indicate the likely consequences on offsprings exposed to in utero hyperglycemia on its growth.

Graphical abstract