Rate- and Region-Dependent Mechanical Properties of Göttingen Minipig Brain Tissue in Simple Shear and Unconfined Compression.

Traumatic brain injury (TBI), particularly from explosive blasts, is a major cause of casualties in modern military conflicts. Computational models are an important tool in understanding the underlying biomechanics of TBI but are highly dependent on the mechanical properties of soft tissue to produce accurate results. Reported material properties of brain tissue can vary by several orders of magnitude between studies, and no published set of material parameters exists for porcine brain tissue at strain rates relevant to blast. In this work, brain tissue from the brainstem, cerebellum, and cerebrum of freshly euthanized adolescent male Göttingen minipigs was tested in simple shear and unconfined compression at strain rates ranging from quasi-static (QS) to 300 s-1. Brain tissue showed significant strain rate stiffening in both shear and compression. Minimal differences were seen between different regions of the brain. Both hyperelastic and hyper-viscoelastic constitutive models were fit to experimental stress, considering data from either a single loading mode (unidirectional) or two loading modes together (bidirectional). The unidirectional hyper-viscoelastic models with an Ogden hyperelastic representation and a one-term Prony series best captured the response of brain tissue in all regions and rates. The bidirectional models were generally able to capture the response of the tissue in high-rate shear and all compression modes, but not the QS shear. Our constitutive models describe the first set of material parameters for porcine brain tissue relevant to loading modes and rates seen in blast injury.

A Strain Rate-Dependent Constitutive Model for Göttingen Minipig Cerebral Arteries.

Computational simulations of traumatic brain injury (TBI) are commonly used to advance understanding of the injury-pathology relationship, tissue damage thresholds, and design of protective equipment such as helmets. Both human and animal TBI models have developed substantially over recent decades, partially due to the inclusion of more detailed brain geometry and representation of tissues like cerebral blood vessels. Explicit incorporation of vessels dramatically affects local strain and enables researchers to investigate TBI-induced damage to the vasculature. While some studies have indicated that cerebral arteries are rate-dependent, no published experimentally based, rate-sensitive constitutive models of cerebral arteries exist. In this work, we characterize the mechanical properties of axially failed porcine arteries, both quasi-statically (0.01 s-1) and at high rate (>100 s-1), and propose a rate-sensitive model to fit the data. We find that the quasi-static and high-rate stress-stretch curves become significantly different (p < 0.05) above a stretch of 1.23. We additionally find a significant change in both failure stretch and stress as a result of strain rate. The stress-stretch curve is then modeled as a Holzapfel-Gasser-Ogden material, with a Prony series added to capture the effects of viscoelasticity. Ultimately, this paper demonstrates that rate dependence should be considered in the material properties of cerebral arteries undergoing high strain-rate deformations and provides a ready-to-use model for finite element implementation.

Injury Length and Arteriole Constriction Shape Clot Growth and Blood-Flow Acceleration in a Mouse Model of Thrombosis.

OBJECTIVE: Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased injury severity translates to blood-flow modulation. Here, we investigated interconnections between injury length, clot growth, and blood flow in a mouse model of laser-induced thrombosis. Approach and Results: Using intravital microscopy, we analyzed 59 clotting events collected from the cremaster arteriole of 14 adult mice. We regarded injury length as a measure of injury severity. The injury caused transient constriction upstream and downstream of the injury site resulting in a 50% reduction in arteriole diameter. The amount of platelet accumulation and fibrin formation did not depend on arteriole diameter or deformation but displayed an exponentially increasing dependence on injury length. The height of the platelet clot depended linearly on injury length and the arteriole diameter. Upstream arteriolar constriction correlated with delayed upstream velocity increase, which, in turn, determined downstream velocity. Before clot formation, flow velocity positively correlated with the arteriole diameter. After the onset of thrombus growth, flow velocity at the injury site negatively correlated with the arteriole diameter and with the size of the above-clot lumen. CONCLUSIONS: Injury severity increased platelet accumulation and fibrin formation in a persistently steep fashion and, together with arteriole diameter, defined clot height. Arterial constriction and clot formation were characterized by a dynamic change in the blood flow, associated with increased flow velocity.

The importance of modeling the human cerebral vasculature in blunt trauma.

BACKGROUND: Multiple studies describing human head finite element (FE) models have established the importance of including the major cerebral vasculature to improve the accuracy of the model predictions. However, a more detailed network of cerebral vasculature, including the major veins and arteries as well as their branch vessels, can further enhance the model-predicted biomechanical responses and help identify correlates to observed blunt-induced brain injury. METHODS: We used an anatomically accurate three-dimensional geometry of a 50th percentile U.S. male head that included the skin, eyes, sinuses, spine, skull, brain, meninges, and a detailed network of cerebral vasculature to develop a high-fidelity model. We performed blunt trauma simulations and determined the intracranial pressure (ICP), the relative displacement (RD), the von Mises stress, and the maximum principal strain. We validated our detailed-vasculature model by comparing the model-predicted ICP and RD values with experimental measurements. To quantify the influence of including a more comprehensive network of brain vessels, we compared the biomechanical responses of our detailed-vasculature model with those of a reduced-vasculature model and a no-vasculature model. RESULTS: For an inclined frontal impact, the predicted ICP matched well with the experimental results in the fossa, frontal, parietal, and occipital lobes, with peak-pressure differences ranging from 2.4% to 9.4%. For a normal frontal impact, the predicted ICP matched the experimental results in the frontal lobe and lateral ventricle, with peak-pressure discrepancies equivalent to 1.9% and 22.3%, respectively. For an offset parietal impact, the model-predicted RD matched well with the experimental measurements, with peak RD differences of 27% and 24% in the right and left cerebral hemispheres, respectively. Incorporating the detailed cerebral vasculature did not influence the ICP but redistributed the brain-tissue stresses and strains by as much as 30%. In addition, our detailed-vasculature model predicted strain reductions by as much as 28% when compared to current reduced-vasculature FE models that only include the major cerebral vessels. CONCLUSIONS: Our study highlights the importance of including a detailed representation of the cerebral vasculature in FE models to more accurately estimate the biomechanical responses of the human brain to blunt impact.

A 3-D virtual human thermoregulatory model to predict whole-body and organ-specific heat-stress responses.

OBJECTIVE: This study aimed at assessing the risks associated with human exposure to heat-stress conditions by predicting organ- and tissue-level heat-stress responses under different exertional activities, environmental conditions, and clothing. METHODS: In this study, we developed an anatomically detailed three-dimensional thermoregulatory finite element model of a 50th percentile U.S. male, to predict the spatiotemporal temperature distribution throughout the body. The model accounts for the major heat transfer and thermoregulatory mechanisms, and circadian-rhythm effects. We validated our model by comparing its temperature predictions of various organs (brain, liver, stomach, bladder, and esophagus), and muscles (vastus medialis and triceps brachii) under normal resting conditions (errors between 0.0 and 0.5 °C), and of rectum under different heat-stress conditions (errors between 0.1 and 0.3 °C), with experimental measurements from multiple studies. RESULTS: Our simulations showed that the rise in the rectal temperature was primarily driven by the activity level (~ 94%) and, to a much lesser extent, environmental conditions or clothing considered in our study. The peak temperature in the heart, liver, and kidney were consistently higher than in the rectum (by ~ 0.6 °C), and the entire heart and liver recorded higher temperatures than in the rectum, indicating that these organs may be more susceptible to heat injury. CONCLUSION: Our model can help assess the impact of exertional and environmental heat stressors at the organ level and, in the future, evaluate the efficacy of different whole-body or localized cooling strategies in preserving organ integrity.

Animal Orientation Affects Brain Biomechanical Responses to Blast-Wave Exposure.

In this study, we investigated how animal orientation within a shock tube influences the biomechanical responses of the brain and cerebral vasculature of a rat when exposed to a blast wave. Using three-dimensional finite element (FE) models, we computed the biomechanical responses when the rat was exposed to the same blast-wave overpressure (100 kPa) in a prone (P), vertical (V), or head-only (HO) orientation. We validated our model by comparing the model-predicted and the experimentally measured brain pressures at the lateral ventricle. For all three orientations, the maximum difference between the predicted and measured pressures was 11%. Animal orientation markedly influenced the predicted peak pressure at the anterior position along the midsagittal plane of the brain (P = 187 kPa; V = 119 kPa; and HO = 142 kPa). However, the relative differences in the predicted peak pressure between the orientations decreased at the medial (21%) and posterior (7%) positions. In contrast to the pressure, the peak strain in the prone orientation relative to the other orientations at the anterior, medial, and posterior positions was 40-88% lower. Similarly, at these positions, the cerebral vasculature strain in the prone orientation was lower than the strain in the other orientations. These results show that animal orientation in a shock tube influences the biomechanical responses of the brain and the cerebral vasculature of the rat, strongly suggesting that a direct comparison of changes in brain tissue observed from animals exposed at different orientations can lead to incorrect conclusions.

Effects of body size and load carriage on lower-extremity biomechanical responses in healthy women.

BACKGROUND: Musculoskeletal injuries, such as stress fractures, are the single most important medical impediment to military readiness in the U.S. Army. While multiple studies have established race- and sex-based risks associated with a stress fracture, the role of certain physical characteristics, such as body size, on stress-fracture risk is less conclusive. METHODS: In this study, we investigated the effects of body size and load carriage on lower-extremity joint mechanics, tibial strain, and tibial stress-fracture risk in women. Using individualized musculoskeletal-finite-element-models of 21 women of short, medium, and tall statures (n = 7 in each group), we computed the joint mechanics and tibial strains while running on a treadmill at 3.0 m/s without and with a load of 11.3 or 22.7 kg. We also estimated the stress-fracture risk using a probabilistic model of bone damage, repair, and adaptation. RESULTS: Under all load conditions, the peak plantarflexion moment for tall women was higher than those in short women (p < 0.05). However, regardless of the load condition, we did not observe differences in the strains and the stress-fracture risk between the stature groups. When compared to the no-load condition, a 22.7-kg load increased the peak hip extension and flexion moments for all stature groups (p < 0.05). However, when compared to the no-load condition, the 22.7-kg load increased the strains and the stress-fracture risk in short and medium women (p < 0.05), but not in tall women. CONCLUSION: These results show that women of different statures adjust their gait mechanisms differently when running with external load. This study can educate the development of new strategies to help reduce the risk of musculoskeletal injuries in women while running with external load.

Regional Changes in Density and Microarchitecture in the Ultradistal Tibia of Female Recruits After U.S. Army Basic Combat Training.

Musculoskeletal injuries, such as stress fracture, are responsible for over 10-million lost-duty days among U.S. Army Soldiers. During Basic Combat Training (BCT), an 8- to 10-week program that transforms civilians into Soldiers, women are four times more likely than men to sustain a stress fracture. In this work, we performed high-resolution peripheral quantitative computed tomography scans on the ultradistal tibia of 90 female recruits [age = 21.5 ± 3.3 (mean ± standard deviation) years] before the start of BCT and after 8 weeks into BCT. Then, we divided the scanned bone volume into four sectors-lateral, posterior, medial, and anterior-and computed the bone density and microarchitectural parameters in each of the four sectors pre- and post-BCT. We used linear mixed models to estimate the mean difference for bone density and microarchitectural parameters, while controlling for age, race, and pre-BCT body mass index. Our results revealed that the total volumetric bone mineral density, trabecular volumetric bone mineral density, and trabecular thickness increased (p < 0.05) in each of the four sectors. In addition, cortical thickness and trabecular bone volume/total volume increased in both medial and posterior sectors (p < 0.05). Overall, six and five out of nine parameters improved in the medial and posterior sectors, respectively, after BCT. In conclusion, the heightened physical activity during BCT led to the most beneficial bone adaptation in the medial and posterior sectors of the ultradistal tibia, which is indicative of higher loading in these sectors during activities performed in the course of BCT.

Material Properties of Rat Middle Cerebral Arteries at High Strain Rates.

Traumatic brain injury (TBI), resulting from either impact- or nonimpact blast-related mechanisms, is a devastating cause of death and disability. The cerebral blood vessels, which provide critical support for brain tissue in both health and disease, are commonly injured in TBI. However, little is known about how vessels respond to traumatic loading, particularly at rates relevant to blast. To better understand vessel responses to trauma, the objective of this project was to characterize the high-rate response of passive cerebral arteries. Rat middle cerebral arteries (MCAs) were isolated and subjected to high-rate deformation in the axial direction. Vessels were perfused at physiological pressures and stretched to failure at strain rates ranging from approximately 100 to 1300 s-1. Although both in vivo stiffness and failure stress increased significantly with strain rate, failure stretch did not depend on rate.

Differences in Trabecular Microarchitecture and Simplified Boundary Conditions Limit the Accuracy of Quantitative Computed Tomography-Based Finite Element Models of Vertebral Failure.

Vertebral fractures are common in the elderly, but efforts to reduce their incidence have been hampered by incomplete understanding of the failure processes that are involved. This study's goal was to elucidate failure processes in the lumbar vertebra and to assess the accuracy of quantitative computed tomography (QCT)-based finite element (FE) simulations of these processes. Following QCT scanning, spine segments (n = 27) consisting of L1 with adjacent intervertebral disks and neighboring endplates of T12 and L2 were compressed axially in a stepwise manner. A microcomputed tomography scan was performed at each loading step. The resulting time-lapse series of images was analyzed using digital volume correlation (DVC) to quantify deformations throughout the vertebral body. While some diversity among vertebrae was observed on how these deformations progressed, common features were large strains that developed progressively in the superior third and, concomitantly, in the midtransverse plane, in a manner that was associated with spatial variations in microstructural parameters such as connectivity density. Results of FE simulations corresponded qualitatively to the measured failure patterns when boundary conditions were derived from DVC displacements at the endplate. However, quantitative correspondence was often poor, particularly when boundary conditions were simplified to uniform compressive loading. These findings suggest that variations in trabecular microstructure are one cause of the differences in failure patterns among vertebrae and that both the lack of incorporation of these variations into QCT-based FE models and the oversimplification of boundary conditions limit the accuracy of these models in simulating vertebral failure.

A cross-sectional study of the effects of load carriage on running characteristics and tibial mechanical stress: implications for stress-fracture injuries in women.

BACKGROUND: Load carriage is associated with musculoskeletal injuries, such as stress fractures, during military basic combat training. By investigating the influence of load carriage during exercises on the kinematics and kinetics of the body and on the biomechanical responses of bones, such as the tibia, we can quantify the role of load carriage on bone health. METHODS: We conducted a cross-sectional study using an integrated musculoskeletal-finite-element model to analyze how the amount of load carriage in women affected the kinematics and kinetics of the body, as well as the tibial mechanical stress during running. We also compared the biomechanics of walking (studied previously) and running under various load-carriage conditions. RESULTS: We observed substantial changes in both hip kinematics and kinetics during running when subjects carried a load. Relative to those observed during running without load, the joint reaction forces at the hip increased by an average of 49.1% body weight when subjects carried a load that was 30% of their body weight (ankle, 4.8%; knee, 20.6%). These results indicate that the hip extensor muscles in women are the main power generators when running with load carriage. When comparing running with walking, finite element analysis revealed that the peak tibial stress during running (tension, 90.6 MPa; compression, 136.2 MPa) was more than three times as great as that during walking (tension, 24.1 MPa; compression, 40.3 MPa), whereas the cumulative stress within one stride did not differ substantially between running (15.2 MPa · s) and walking (13.6 MPa · s). CONCLUSIONS: Our findings highlight the critical role of hip extensor muscles and their potential injury in women when running with load carriage. More importantly, our results underscore the need to incorporate the cumulative effect of mechanical stress when evaluating injury risk under various exercise conditions. The results from our study help to elucidate the mechanisms of stress fracture in women.

Effect of Interstitial Fluid Pressure on Ultrasound Axial Strain and Axial Shear Strain Elastography.

Ultrasound elastography is an imaging modality that has been used to diagnose tumors of the breast, thyroid, and prostate. Both axial strain elastography and axial shear strain elastography (ASSE) have shown significant potentials to differentiate between benign and malignant tumors. Elevated interstitial fluid pressure (IFP) is a characteristic of many malignant tumors and a major barrier in targeted drug delivery therapies. This parameter, however, has not received significant attention in ultrasound elastography and, in general, in most diagnostic imaging modalities yet. In this paper, we investigate the effect of an underlying IFP contrast on ultrasound axial strain and axial shear strain imaging using finite element analysis. Our results show that an underlying contrast in IFP creates a new contrast mechanism in both the axial strain and axial shear strain elastographic images. This information might be important for a better interpretation of elastographic images of tumors.

An Integrated Musculoskeletal-Finite-Element Model to Evaluate Effects of Load Carriage on the Tibia During Walking.

Prior studies have assessed the effects of load carriage on the tibia. Here, we expand on these studies and investigate the effects of load carriage on joint reaction forces (JRFs) and the resulting spatiotemporal stress/strain distributions in the tibia. Using full-body motion and ground reaction forces from a female subject, we computed joint and muscle forces during walking for four load carriage conditions. We applied these forces as physiological loading conditions in a finite-element (FE) analysis to compute strain and stress. We derived material properties from computed tomography (CT) images of a sex-, age-, and body mass index-matched subject using a mesh morphing and mapping algorithm, and used them within the FE model. Compared to walking with no load, the knee JRFs were the most sensitive to load carriage, increasing by as much as 26.2% when carrying a 30% of body weight (BW) load (ankle: 16.4% and hip: 19.0%). Moreover, our model revealed disproportionate increases in internal JRFs with increases in load carriage, suggesting a coordinated adjustment in the musculature functions in the lower extremity. FE results reflected the complex effects of spatially varying material properties distribution and muscular engagement on tibial biomechanics during walking. We observed high stresses on the anterior crest and the medial surface of the tibia at pushoff, whereas high cumulative stress during one walking cycle was more prominent in the medioposterior aspect of the tibia. Our findings reinforce the need to include: (1) physiologically accurate loading conditions when modeling healthy subjects undergoing short-term exercise training and (2) the duration of stress exposure when evaluating stress-fracture injury risk. As a fundamental step toward understanding the instantaneous effect of external loading, our study presents a means to assess the relationship between load carriage and bone biomechanics.

Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves.

Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36-45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups.

Elastic Anisotropy of Trabecular Bone in the Elderly Human Vertebra.

Knowledge of the nature of the elastic symmetry of trabecular bone is fundamental to the study of bone adaptation and failure. Previous studies have classified human vertebral trabecular bone as orthotropic or transversely isotropic but have typically obtained samples from only selected regions of the centrum. In this study, the elastic symmetry of human vertebral trabecular bone was characterized using microfinite element (µFE) analyses performed on 1019 cubic regions of side length equal to 5 mm, obtained via thorough sampling of the centrums of 18 human L1 vertebrae (age = 81.17 ± 7.7 yr; eight males and ten females). An optimization procedure was used to find the closest orthotropic representation of the resulting stiffness tensor for each cube. The orthotropic elastic constants and orientation of the principal elastic axes were then recorded for each cube and were compared to the constants predicted from Cowin's fabric-based constitutive model (Cowin, 1985, "The Relationship Between the Elasticity Tensor and the Fabric Tensor," Mech. Mater., 4(2), pp. 137-147.) and the orientation of the principal axes of the fabric tensor, respectively. Deviations from orthotropy were quantified by the "orthotropic error" (van Rietbergen et al., 1996, "Direct Mechanics Assessment of Elastic Symmetries and Properties of Trabecular Bone Architecture," J. Biomech., 29(12), pp. 1653-1657), and deviations from transverse isotropy were determined by statistical comparison of the secondary and tertiary elastic moduli. The orthotropic error was greater than 50% for nearly half of the cubes, and the secondary and tertiary moduli differed from one another (p < 0.0001). Both the orthotropic error and the difference between secondary and tertiary moduli decreased with increasing bone volume fraction (BV/TV; p ≤ 0.007). Considering only the cubes with an orthotropic error less than 50%, only moderate correlations were observed between the fabric-based and the µFE-computed elastic moduli (R2 ≥ 0.337; p < 0.0001). These results indicate that when using a criterion of 5 mm for a representative volume element (RVE), transverse isotropy or orthotropy cannot be assumed for elderly human vertebral trabecular bone. Particularly at low values of BV/TV, this criterion does not ensure applicability of theories of continuous media. In light of the very sparse and inhomogeneous microstructure found in the specimens analyzed in this study, further work is needed to establish guidelines for selecting a RVE within the aged vertebral centrum.

Region specific anisotropy and rate dependence of Göttingen minipig brain tissue.

Traumatic brain injury is a major cause of morbidity in civilian as well as military populations. Computational simulations of injurious events are an important tool to understanding the biomechanics of brain injury and evaluating injury criteria and safety measures. However, these computational models are highly dependent on the material parameters used to represent the brain tissue. Reported material properties of tissue from the cerebrum and cerebellum remain poorly defined at high rates and with respect to anisotropy. In this work, brain tissue from the cerebrum and cerebellum of male Göttingen minipigs was tested in one of three directions relative to axon fibers in oscillatory simple shear over a large range of strain rates from 0.025 to 250 s-1. Brain tissue showed significant direction dependence in both regions, each with a single preferred loading direction. The tissue also showed strong rate dependence over the full range of rates considered. Transversely isotropic hyper-viscoelastic constitutive models were fit to experimental data using dynamic inverse finite element models to account for wave propagation observed at high strain rates. The fit constitutive models predicted the response in all directions well at rates below 100 s-1, after which they adequately predicted the initial two loading cycles, with the exception of the 250 s-1 rate, where models performed poorly. These constitutive models can be readily implemented in finite element packages and are suitable for simulation of both conventional and blast injury in porcine, especially Göttingen minipig, models.

Effect of specimen-specific anisotropic material properties in quantitative computed tomography-based finite element analysis of the vertebra.

Intra- and inter-specimen variations in trabecular anisotropy are often ignored in quantitative computed tomography (QCT)-based finite element (FE) models of the vertebra. The material properties are typically estimated solely from local variations in bone mineral density (BMD), and a fixed representation of elastic anisotropy ("generic anisotropy") is assumed. This study evaluated the effect of incorporating specimen-specific, trabecular anisotropy on QCT-based FE predictions of vertebral stiffness and deformation patterns. Orthotropic material properties estimated from microcomputed tomography data ("specimen-specific anisotropy"), were assigned to a large, columnar region of the L1 centrum (n = 12), and generic-anisotropic material properties were assigned to the remainder of the vertebral body. Results were compared to FE analyses in which generic-anisotropic properties were used throughout. FE analyses were also performed on only the columnar regions. For the columnar regions, the axial stiffnesses obtained from the two categories of material properties were uncorrelated with each other (p = 0.604), and the distributions of minimum principal strain were distinctly different (p ≤ 0.022). In contrast, for the whole vertebral bodies in both axial and flexural loading, the stiffnesses obtained using the two categories of material properties were highly correlated (R2 > 0.82, p < 0.001) with, and were no different (p > 0.359) from, each other. Only moderate variations in strain distributions were observed between the two categories of material properties. The contrasting results for the columns versus vertebrae indicate a large contribution of the peripheral regions of the vertebral body to the mechanical behavior of this bone. In companion analyses on the effect of the degree of anisotropy (DA), the axial stiffnesses of the trabecular column (p < 0.001) and vertebra (p = 0.007) increased with increasing DA. These findings demonstrate the need for accurate modeling of the peripheral regions of the vertebral body in analyses of the mechanical behavior of the vertebra.

A 3-D virtual human model for simulating heat and cold stress.

In this study, we extended our previously developed anatomically detailed three-dimensional (3-D) thermoregulatory virtual human model for predicting heat stress to allow for predictions of heat and cold stress in one unified model. Starting with the modified Pennes bioheat transfer equation to estimate the spatiotemporal temperature distribution within the body as the underlying modeling structure, we developed a new formulation to characterize the spatial variation of blood temperature between body elements and within the limbs. We also implemented the means to represent heat generated from shivering and skin blood flow that apply to air exposure and water immersion. Then, we performed simulations and validated the model predictions with experimental data from nine studies, representing a wide range of heat- and cold-stress conditions in air and water and physical activities. We observed excellent agreement between model predictions and measured data, with average root mean squared errors of 0.2°C for core temperature, 0.9°C for mean skin temperature, and 27 W for heat from shivering. We found that a spatially varying blood temperature profile within the limbs was crucial to accurately predict core body temperature changes during very cold exposures. Our 3-D thermoregulatory virtual human model consistently predicted the body's thermal state accurately for each of the simulated hot and cold environmental conditions and exertional heat stress. As such, it serves as a reliable tool to assess whole body, localized tissue, and, potentially, organ-specific injury risks, helping develop injury prevention and mitigation strategies in a systematic and expeditious manner.NEW & NOTEWORTHY This work provides a new, unified modeling framework to accurately predict the human body's thermal response to both heat and cold stress caused by environmental conditions and exertional physical activity in one mathematical model. We show that this 3-D anatomically detailed model accurately predicts the spatiotemporal temperature distribution in the body under extreme conditions for exposures to air and water and could be used to help design medical interventions and countermeasures to prevent injuries.

A biomechanical-based approach to scale blast-induced molecular changes in the brain.

Animal studies provide valuable insights on how the interaction of blast waves with the head may injure the brain. However, there is no acceptable methodology to scale the findings from animals to humans. Here, we propose an experimental/computational approach to project observed blast-induced molecular changes in the rat brain to the human brain. Using a shock tube, we exposed rats to a range of blast overpressures (BOPs) and used a high-fidelity computational model of a rat head to correlate predicted biomechanical responses with measured changes in glial fibrillary acidic protein (GFAP) in rat brain tissues. Our analyses revealed correlates between model-predicted strain rate and measured GFAP changes in three brain regions. Using these correlates and a high-fidelity computational model of a human head, we determined the equivalent BOPs in rats and in humans that induced similar strain rates across the two species. We used the equivalent BOPs to project the measured GFAP changes in the rat brain to the human. Our results suggest that, relative to the rat, the human requires an exposure to a blast wave of a higher magnitude to elicit similar brain-tissue responses. Our proposed methodology could assist in the development of safety guidelines for blast exposure.

A new material mapping procedure for quantitative computed tomography-based, continuum finite element analyses of the vertebra.

Inaccuracies in the estimation of material properties and errors in the assignment of these properties into finite element models limit the reliability, accuracy, and precision of quantitative computed tomography (QCT)-based finite element analyses of the vertebra. In this work, a new mesh-independent, material mapping procedure was developed to improve the quality of predictions of vertebral mechanical behavior from QCT-based finite element models. In this procedure, an intermediate step, called the material block model, was introduced to determine the distribution of material properties based on bone mineral density, and these properties were then mapped onto the finite element mesh. A sensitivity study was first conducted on a calibration phantom to understand the influence of the size of the material blocks on the computed bone mineral density. It was observed that varying the material block size produced only marginal changes in the predictions of mineral density. Finite element (FE) analyses were then conducted on a square column-shaped region of the vertebra and also on the entire vertebra in order to study the effect of material block size on the FE-derived outcomes. The predicted values of stiffness for the column and the vertebra decreased with decreasing block size. When these results were compared to those of a mesh convergence analysis, it was found that the influence of element size on vertebral stiffness was less than that of the material block size. This mapping procedure allows the material properties in a finite element study to be determined based on the block size required for an accurate representation of the material field, while the size of the finite elements can be selected independently and based on the required numerical accuracy of the finite element solution. The mesh-independent, material mapping procedure developed in this study could be particularly helpful in improving the accuracy of finite element analyses of vertebroplasty and spine metastases, as these analyses typically require mesh refinement at the interfaces between distinct materials. Moreover, the mapping procedure is not specific to the vertebra and could thus be applied to many other anatomic sites.