Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.     

Development,Validation, and Application of a Parametric Pediatric Head Finite Element Model for Impact Simulations

In this study, a statistical model of cranium geometry for 0- to 3-month-old children was developed by analyzing 11 CT scans using a combination of principal component analysis and multivariate regression analysis. Radial basis function was used to morph the geometry of a baseline child head finite element (FE) model into models with geometries representing a newborn, a 1.5-month-old, and a 3-month-old infant head. These three FE models were used in a parametric study of near-vertex impact conditions to quantify the sensitivity of different material parameters. Finally, model validation was conducted against peak head accelerations in cadaver tests under different impact conditions, and optimization techniques were used to determine the material properties. The results showed that the statistical model of cranium geometry produced realistic cranium size and shape, suture size, and skull/suture thickness, for 0- to 3-month-old children. The three pediatric head models generated by morphing had mesh quality comparable to the baseline model. The elastic modulus of skull had a greater effect on most head impact response measurements than other parameters. Head geometry was a significant factor affecting the maximal principal stress of the skull (p = 0.002) and maximal principal strain of the suture (p = 0.021) after controlling for the skull material. Compared with the newborn head, the 3-month-old head model produced 6.5% higher peak head acceleration, 64.8% higher maximal principal stress, and 66.3% higher strain in the suture. However, in the skull, the 3-month-old model produced 25.7% lower maximal principal stress and 11.5% lower strain than the newborn head. Material properties of the brain had little effects on head acceleration and strain/stress within the skull and suture. Elastic moduli of the skull, suture, dura, and scalp determined using optimization techniques were within reported literature ranges and produced impact response that closely matched those measured in previous cadaver tests. The method developed in this study made it possible to investigate the age effects from geometry changes on pediatric head impact responses. The parametric study demonstrated that it is important to consider the material properties and geometric variations together when estimating pediatric head responses and predicting head injury risks.     

Parametric Comparisons of Intracranial Mechanical Responses from Three Validated Finite Element Models of the Human Head

A number of human head finite element (FE) models have been developed from different research groups over the years to study the mechanisms of traumatic brain injury. These models can vary substantially in model features and parameters, making it important to evaluate whether simulation results from one model are readily comparable with another, and whether response-based injury thresholds established from a specific model can be generalized when a different model is employed. The purpose of this study is to parametrically compare regional brain mechanical responses from three validated head FE models to test the hypothesis that regional brain responses are dependent on the specific head model employed as well as the region of interest (ROI). The Dartmouth Scaled and Normalized Model (DSNM), the Simulated Injury Monitor (SIMon), and the Wayne State University Head Injury Model (WSUHIM) were selected for comparisons. For model input, 144 unique kinematic conditions were created to represent the range of head impacts sustained by male collegiate hockey players during play. These impacts encompass the 50th, 95th, and 99th percentile peak linear and rotational accelerations at 16 impact locations around the head. Five mechanical variables (strain, strain rate, strain × strain rate, stress, and pressure) in seven ROIs reported from the FE models were compared using Generalized Estimating Equation statistical models. Highly significant differences existed among FE models for nearly all output variables and ROIs. The WSUHIM produced substantially higher peak values for almost all output variables regardless of the ROI compared to the DSNM and SIMon models (p < 0.05). DSNM also produced significantly different stress and pressure compared with SIMon for all ROIs (p < 0.05), but such differences were not consistent across ROIs for other variables. Regardless of FE model, most output variables were highly correlated with linear and rotational peak accelerations. The significant disparities in regional brain responses across head models regardless of the output variables strongly suggest that model-predicted brain responses from one study should not be extended to other studies in which a different model is utilized. Consequently, response-based injury tolerance thresholds from a specific model should not be generalized to other studies either in which a different model is used. However, the similar relationships between regional responses and the linear/rotational peak accelerations suggest that each FE model can be used independently to assess regional brain responses to impact simulations in order to perform statistical correlations with medical images and/or well-selected experiments with documented injury findings.     

交通事故中颈部损伤的有限元模型研究现状

汽车交通事故是当今世界造成儿童和年轻人死亡的主要原因,其中头颈部的损伤是交通事故中最为常见的致命性损伤.由于碰撞条件复杂和不可重复,再加上尸体和动物研究的伦理问题,致使头颈部损伤机理的实验研究存在较大困难,因此有限元分析在人体头-颈部耐撞性研究得到广泛应用.有限元方法的应用对于交通事故中不同撞击条件损伤程度的评估以及汽车工业损伤保护标准的开发起重要作用.本文从头颈部损伤机理、有限元几何模型获取、有限元网格划分,及所研究材料特性和实验验证方法等方面,对近年来国际上开发的应用有限元模型对交通事故中的头颈部损伤的研究现状进行综述,并对各个模型的优势和特点加以分析归纳,并对未来相关研究提出建议.     

Rheological properties of the tissues of the central nervous system: a review

Knowledge of the biomechanical properties of central nervous system (CNS) tissues is important for understanding mechanisms and thresholds for injury, and aiding development of computer or surrogate models of these tissues. Many investigations have been conducted to estimate the properties of CNS tissues including under shear, compressive and tensile loading, however there is much variability in this body of literature, making it difficult to separate the material properties from effects that result from a given experimental protocol. This review summarises previous studies of brain and spinal cord properties; discussing their main findings and points of difference, and displays the reported data on comparable scales. Additionally, based on the observed effects of methodological choices on reported tissue properties, recommendations for future studies of brain and spinal cord properties are made.     

研究颅脑交通伤的有限元模型的建立及验证

建立基于人体解剖学结构的HBM(Human body model)头部三维有限元模型.详细描述了人体头部的主要解剖学结构,模型由头皮、颅骨、硬脑膜、脑脊液、软脑膜、大脑、小脑、脑室、脑干、脑镰和脑幕等组成.采用人体头部碰撞实验数据,比较了实验与仿真中头部的动力学响应和颅内压力分布参数,对头部有限元模型进行了验证.结果表明,该模型具有较好的生物逼真度,可以用来分析研究车辆交通事故中颅脑创伤和损伤机理.     

Development of a Metric for Predicting Brain Strain Responses Using Head Kinematics

Diffuse brain injuries are caused by excessive brain deformation generated primarily by rapid rotational head motion. Metrics that describe the severity of brain injury based on head motion often do not represent the governing physics of brain deformation, rendering them ineffective over a broad range of head impact conditions. This study develops a brain injury metric based on the response of a second-order mechanical system, and relates rotational head kinematics to strain-based brain injury metrics: maximum principal strain (MPS) and cumulative strain damage measure (CSDM). This new metric, universal brain injury criterion (UBrIC), is applicable over a broad range of kinematics encountered in automotive crash and sports. Efficacy of UBrIC was demonstrated by comparing it to MPS and CSDM predicted in 1600 head impacts using two different finite element (FE) brain models. Relative to existing metrics, UBrIC had the highest correlation with the FE models, and performed better in most impact conditions. While UBrIC provides a reliable measurement for brain injury assessment in a broad range of head impact conditions, and can inform helmet and countermeasure design, an injury risk function was not incorporated into its current formulation until validated strain-based risk functions can be developed and verified against human injury data.     

Evaluation of micro tip pressure transducers for the measurement of intracerebral pressure transients induced by fluid percussion.

We describe the application of MIKRO TIP miniature pressure transducers (MPT) for the in vivo measurement of intracerebral stresses induced by traumatic brain injury (TBI). In order to test the linearity of these transducers pressure pulses of different amplitudes (duration approximately 10ms) were generated in a closed calibration chamber. A piezoelectric pressure transducer (PPT) served as the reference measure. A linear correlation was found within the pressure range between 0.57 and 5.09 bar (R2 = 0.998). The frequency transmission characteristics of the MPTs are comparable to the PPT. In three juvenile swines (6 weeks of age) pressures within the brain tissue were induced by fluid percussion (FP) and were measured in the anterior, middle, and posterior cranial cavity as well as in the extracranial part of the medulla oblongata. The data obtained in our experiments agree with the basic biomechanics of FP known from studies in cats and rabbits. Due to their small size, MPTs can be applied in living animals. Stereotaxic positioning of these catheters at any site of the brain and spinal cord requires only minimal surgery. Therefore, MPTs are useful in evaluating animal models of brain injury and in generating input data for computational models of head injury as well as to validate the mathematical results of such models with experimental data.     

Influence of mesh density,cortical thickness and material properties on human rib fracture prediction

The purpose of this paper was to investigate the sensitivity of the structural responses and bone fractures of the ribs to mesh density, cortical thickness, and material properties so as to provide guidelines for the development of finite element (FE) thorax models used in impact biomechanics. Subject-specific FE models of the second, fourth, sixth and tenth ribs were developed to reproduce dynamic failure experiments. Sensitivity studies were then conducted to quantify the effects of variations in mesh density, cortical thickness, and material parameters on the model-predicted reaction force–displacement relationship, cortical strains, and bone fracture locations for all four ribs. Overall, it was demonstrated that rib FE models consisting of 2000–3000 trabecular hexahedral elements (weighted element length 2–3 mm) and associated quadrilateral cortical shell elements with variable thickness more closely predicted the rib structural responses and bone fracture force–failure displacement relationships observed in the experiments (except the fracture locations), compared to models with constant cortical thickness. Further increases in mesh density increased computational cost but did not markedly improve model predictions. A ±30% change in the major material parameters of cortical bone lead to a ?16.7 to 33.3% change in fracture displacement and ?22.5 to +19.1% change in the fracture force. The results in this study suggest that human rib structural responses can be modeled in an accurate and computationally efficient way using (a) a coarse mesh of 2000–3000 solid elements, (b) cortical shells elements with variable thickness distribution and (c) a rate-dependent elastic–plastic material model.     

有限元分析法在脊髓损伤生物力学中的研究进展

脊髓损伤时的变化非常复杂,动物模型很难精确模拟损伤环境以及测量局部组织的生物力学属性,而有限元模型则可以通过分析脊髓组织的应力和应变分布,从生物力学角度为脊髓损伤的病理研究和治疗提供一个更为高效的方法。目前,有限元模型已被广泛应用,并与动物实验模型相辅相成。本文回顾了有限元法在脊髓损伤中的研究进展,对有限元法在脊髓本体建模、脊髓损伤的生物力学行为及其临床应用等方面的研究现况进行归纳及总结,以期为临床脊髓损伤问题提供更为全面的理论参考。     

Finite element analysis of the spine: towards a framework of verification, validation and sensitivity analysis

A number of papers have recently emphasised the importance of verification, validation and sensitivity testing in computational studies within the field of biomechanical engineering. This review examines the methods used in the development of spinal finite element models with a view to a standardised framework of verification, validation and sensitivity analysis. The scope of this paper is restricted to models of the vertebra, the intervertebral disc and short spinal segments. In the case of single vertebral models, specimen-specific methods have been developed, which allow direct validation against experimental tests. The focus of intervertebral disc modelling has been on representing the complex material properties and further sensitivity testing is required to fully understand the relative roles of these input parameters. In order to construct complex multi-component short segment models, many geometric and material parameters are required, some of which are yet to be fully characterised. There are also major challenges in terms of short segment model validation. Throughout the review, areas of good practise are highlighted and recommendations for future development are proposed, taking a step towards more robust spinal modelling procedures, promoting acceptance from the wider biomechanics community.     

具有详细解剖学结构的1岁学步儿童头部有限元模型构建及验证

目的构建详细的1岁学步儿童头部有限元模型,探究其颅脑损伤机制,完善人体有限元生物力学模型数据库。方法基于我国1岁儿童真实详细的头部CT数据,借助医学软件Mimics获得头部几何结构数据,利用逆向工程软件划分NURBS曲面片和构建工程模型,利用有限元前处理软件划分网格,参照解剖学和尸体实验等数据,验证1岁学步儿童头部有限元模型的有效性并初步分析其损伤机制。结果构建了中国男性1岁儿童头部有限元模型,模型包括并区分了大脑及小脑的灰质和白质、海马体、囟门、矢状骨缝、冠状骨缝、脑干、脑室等,几何尺寸符合解剖学统计数据。利用头部模型重构了儿童头部静态压缩尸体实验和跌落尸体实验,结果表明,该头部模型与尸体实验表现了相近的力学特征,验证了模型的有效性。计算表明不同压缩速率下颅骨刚度不同,会导致不同损伤结果。结论所构建的包含详细解剖学结构的1岁儿童头部有限元模型具有较高的生物仿真度,借助构建的模型可分析深部脑组织各部位的详细损伤情况,特别是闭合性颅脑损伤,为相关研究及临床应用提供有效的工具和手段。     

关于头部组织材料性能敏感性对颅内压力响应的研究

应用有限元法 (finiteelementmethod)和试验设计技术 (design of experimentDOE)研究人头部颅骨(skull)、脑脊液 (cerebral spinal fluidCSF)和脑髓 (brain)材料性能的敏感性对颅内因撞击而产生的压力响应。该研究采用头部的有限元模型 ,用三因子、三层次的因子试验设计对影响颅内因撞击而引起的压力的颅骨、脑脊液和脑髓的材料性质的敏感性进行分析。研究结果进一步证实了颅骨、脑脊液、脑髓的材料性能对颅内因撞击而引起的压力的重要影响。本研究为进一步的头部的有限元分析提供了新的见解 ,并提出了对头部组织的材料性能作更进一步的探索。     

重组增强型绿色荧光蛋白慢病毒载体示踪转染的脐血间充质干细胞移植治疗兔股骨头缺血性坏死

背景：目前国内外已有关于人脐血间充质干细胞移植修复鼠脊髓损伤、脑肿瘤、心肌梗死等的报道,将其在特定的条件下向成骨细胞诱导分化的研究也已有报道,但尚未有将脐血间充质干细胞移植治疗动物骨坏死的研究报道。 目的：观察重组增强型绿色荧光蛋白慢病毒载体示踪转染的脐血间充质干细胞移植修复兔股骨头缺血性坏死的效果。 方法：含骨形态发生蛋白2基因质粒与携带重组增强型绿色荧光蛋白的慢病毒载体与脐血间充质干细胞共培养;制作兔股骨头缺损模型,随机分为3组,正常组未作任何处理,对照组骨缺损未进行填充;实验组骨缺损填充重组增强型绿色荧光蛋白慢病毒载体示踪转染的脐血间充质干细胞;分别于治疗4周和8周时股骨头行影像学和组织学观察。 结果与结论：影像学和组织学检查显示实验组治疗4周时即有明显的成骨反应和新骨形成,8周时基本修复股骨头的骨缺损区;对照组治疗4周时骨缺损为纤维结缔组织填充,8周时股骨头缺损周边骨质硬化,骨缺损处充填纤维结缔组织,股骨头骨小梁紊乱。结果显示重组增强型绿色荧光蛋白慢病毒载体示踪转染的脐血间充质干细胞有较强的诱导成骨作用,可以成功的修复股骨头缺损性坏死。     

Viscoelastic Properties of the Rat Brain in the Sagittal Plane: Effects of Anatomical Structure and Age

Rat is the most commonly used animal model for the study of traumatic brain injury. Recent advances in imaging and computational modeling technology offer the promise of biomechanical models capable of resolving individual brain structures and offering greater insight into the causes and consequences of brain injury. However, there is insufficient data on the mechanical properties of brain structures available to populate these models. In this study, we used microindentation to determine viscoelastic properties of different anatomical structures in sagittal slices of juvenile and adult rat brain. We find that the rat brain is spatially heterogeneous in this anatomical plane supporting previous results in the coronal plane. In addition, the brain becomes stiffer and more heterogeneous as the animal matures. This dynamic, region-specific data will support the development of more biofidelic computational models of brain injury biomechanics and the testing of hypotheses about the manner in which different anatomical structures are injured in a head impact.     

Evaluation of Three Animal Models for Concussion and Serious Brain Injury

Three animal models were evaluated in this study involving head impacts of the rat, including the Marmarou drop-weight and two momentum-exchange techniques. In series 1, 36 Wistar rats were hit on the side of the free-moving head using Marmarou’s 450 g impact mass at 4.4, 5.4, and 6.3 m/s. Head acceleration was measured and injuries were observed. The 6.3-m/s side impact resulted in no deaths, no skull fractures, infrequent contusions, and some injuries consistent with diffuse axonal injury. In series 2, 57 Marmarou drop-weight tests were conducted to study head biomechanical responses. Marmarou’s technique involves a head impact followed by prolonged loading into a foam pad under the animal. Based on the literature, the 2 m (6.3 m/s) Marmarou drop causes death, skull fracture, brain and spinal cord contusions, and diffuse axonal injury. These injuries are more severe than that occurring with impact of similar mass and velocity to the free-moving head. Impacts to the free-moving head provide more realistic animal models to study concussion and severe brain injury.     

Application of Optimization Methodology and Specimen-Specific Finite Element Models for Investigating Material Properties of Rat Skull

Finite element (FE) models of rat skull bone samples were developed by reconstructing the three-dimensional geometry of microCT images and voxel-based hexahedral meshes. An optimization-based material identification method was developed to obtain the most favorable material property parameters by minimizing differences in three-point bending test responses between experimental and simulation results. An anisotropic Kriging model and sequential quadratic programming, in conjunction with Latin Hypercube Sampling (LHS), are utilized to minimize the disparity between the experimental and FE model predicted force–deflection curves. A selected number of material parameters, namely Young’s modulus, yield stress, tangent modulus, and failure strain, are varied iteratively using the proposed optimization scheme until the assessment index ‘F’, the objective function comparing simulation and experimental force–deflection curves through least squares, is minimized. Results show that through the application of this method, the optimized models’ force–deflection curves are closely in accordance with the measured data. The average differences between the experimental and simulation data are around 0.378 N (which was 3.3% of the force peak value) and 0.227 N (which was 2.7% of the force peak value) for two different test modes, respectively. The proposed optimization methodology is a potentially useful tool to effectively help establish material parameters. This study represents a preliminary effort in the development and validation of FE models for the rat skull, which may ultimately serve to develop a more biofidelic rat head FE model.     

Three-Dimensional Finite Element Models of the Human Pubic Symphysis with Viscohyperelastic Soft Tissues

Three-dimensional finite element (FE) models of human pubic symphyses were constructed from computed tomography image data of one male and one female cadaver pelvis. The pubic bones, interpubic fibrocartilaginous disc and four pubic ligaments were segmented semi-automatically and meshed with hexahedral elements using automatic mesh generation schemes. A two-term viscoelastic Prony series, determined by curve fitting results of compressive creep experiments, was used to model the rate-dependent effects of the interpubic disc and the pubic ligaments. Three-parameter Mooney-Rivlin material coefficients were calculated for the discs using a heuristic FE approach based on average experimental joint compression data. Similarly, a transversely isotropic hyperelastic material model was applied to the ligaments to capture average tensile responses. Linear elastic isotropic properties were assigned to bone. The applicability of the resulting models was tested in bending simulations in four directions and in tensile tests of varying load rates. The model-predicted results correlated reasonably with the joint bending stiffnesses and rate-dependent tensile responses measured in experiments, supporting the validity of the estimated material coefficients and overall modeling approach. This study represents an important and necessary step in the eventual development of biofidelic pelvis models to investigate symphysis response under high-energy impact conditions, such as motor vehicle collisions.