A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to in vitro Models

Due to the prominent role of improvised explosive devices (IEDs) in wounding patterns of U.S. war-fighters in Iraq and Afghanistan, blast injury has risen to a new level of importance and is recognized to be a major cause of injuries to the brain. However, an injury risk-function for microscopic, macroscopic, behavioral, and neurological deficits has yet to be defined. While operational blast injuries can be very complex and thus difficult to analyze, a simplified blast injury model would facilitate studies correlating biological outcomes with blast biomechanics to define tolerance criteria. Blast-induced traumatic brain injury (bTBI) results from the translation of a shock wave in-air, such as that produced by an IED, into a pressure wave within the skull–brain complex. Our blast injury methodology recapitulates this phenomenon in vitro, allowing for control of the injury biomechanics via a compressed-gas shock tube used in conjunction with a custom-designed, fluid-filled receiver that contains the living culture. The receiver converts the air shock wave into a fast-rising pressure transient with minimal reflections, mimicking the intracranial pressure history in blast. We have developed an organotypic hippocampal slice culture model that exhibits cell death when exposed to a 530 ± 17.7-kPa peak overpressure with a 1.026 ± 0.017-ms duration and 190 ± 10.7 kPa-ms impulse in-air. We have also injured a simplified in vitro model of the blood–brain barrier, which exhibits disrupted integrity immediately following exposure to 581 ± 10.0 kPa peak overpressure with a 1.067 ± 0.006-ms duration and 222 ± 6.9 kPa-ms impulse in-air. To better prevent and treat bTBI, both the initiating biomechanics and the ensuing pathobiology must be understood in greater detail. A well-characterized, in vitro model of bTBI, in conjunction with animal models, will be a powerful tool for developing strategies to mitigate the risks of bTBI

A Multiscale Approach to Blast Neurotrauma Modeling: Part I – Development of Novel Test Devices for in vivo and in vitro Blast Injury Models

The loading conditions used in some current in vivo and in vitro blast-induced neurotrauma models may not be representative of real-world blast conditions. To address these limitations, we developed a compressed-gas driven shock tube with different driven lengths that can generate Friedlander-type blasts. The shock tube can generate overpressures up to 650 kPa with durations between 0.3 and 1.1 ms using compressed helium driver gas, and peak overpressures up to 450 kPa with durations between 0.6 and 3 ms using compressed nitrogen. This device is used for short-duration blast overpressure loading for small animal in vivo injury models, and contrasts the more frequently used long duration/high impulse blast overpressures in the literature. We also developed a new apparatus that is used with the shock tube to recreate the in vivo intracranial overpressure response for loading in vitro culture preparations. The receiver device surrounds the culture with materials of similar impedance to facilitate the propagation of a single overpressure pulse through the tissue. This method prevents pressure waves reflecting off the tissue that can cause unrealistic deformation and injury. The receiver performance was characterized using the longest helium-driven shock tube, and produced in-fluid overpressures up to 1500 kPa at the location where a culture would be placed. This response was well correlated with the overpressure conditions from the shock tube (R2 = 0.97). Finite element models of the shock tube and receiver were developed and validated to better elucidate the mechanics of this methodology. A demonstration exposing a culture to the loading conditions created by this system suggest tissue strains less than 5% for all pressure levels simulated, which was well below functional deficit thresholds for strain rates less than 50 s−1. This novel system is not limited to a specific type of culture model and can be modified to reproduce more complex pressure pulses

A Cortical Thickness Mapping Method for the Coxal Bone Using Morphing

As human body finite element models become more integrated with the design of safety countermeasures and regulations, novel models need to be developed that reflect the variation in the population's anthropometry. However, these new models may be missing information which will need to be translated from existing models. During the development of a 5th percentile female occupant model (F05), cortical thickness information of the coxal bone was unavailable due to resolution limits in the computed tomography (CT) scans. In this study, a method for transferring cortical thickness information from a source to a target model with entirely different geometry and architecture is presented. The source and target models were the Global Human Body Models Consortium (GHBMC) 50th percentile male (M50) and F05 coxal bones, respectively. To project the coxal bone cortical thickness from the M50 to the F05, the M50 model was first morphed using a Kriging method with 132 optimized control points to the F05 anthropometry. This technique was found to be accurate with a mean nodal discrepancy of 1.27 mm between the F05 and morphed M50 (mM50) coxal bones. Cortical thickness at each F05 node was determined by taking the average cortical thickness of every mM50 node, non-linearly weighted by its distance to the F05 nodes. The non-linear weighting coefficient, β, had a large effect on the accuracy and smoothness of the projected cortical bone thickness. The optimal projection had β = 4 and was defined when the tradeoff between projection accuracy and smoothness was equal. Finally, a quasi-static pelvis compression was simulated to examine to effect of β. As β, increased from 0 to 4, the failure force decreased by ~100 N, whereas the failure displacement increased by 0.9 mm. Results from quasi-static compression tests of the F05 pelvis were comparable to experimental results. This method could be applied to other anatomical regions where cortical thickness variation is important, such as the femur and ribs and is not limited to GHBMC-family models. Furthermore, this process will aid the development of subject-specific finite element models where accurate cortical bone thickness measurements cannot be obtained

Porcine Head Response to Blast

Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300–2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G’s and were well correlated with peak incident overpressure (R2 = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are presented to provide experimental data for computer model validation

Use of Brain Biomechanical Models for Monitoring Impact Exposure in Contact Sports

Head acceleration measurement sensors are now widely deployed in the field to monitor head kinematic exposure in contact sports. The wealth of impact kinematics data provides valuable, yet challenging, opportunities to study the biomechanical basis of mild traumatic brain injury (mTBI) and subconcussive kinematic exposure. Head impact kinematics are translated into brain mechanical responses through physics-based computational simulations using validated brain models to study the mechanisms of injury. First, this article reviews representative legacy and contemporary brain biomechanical models primarily used for blunt impact simulation. Then, it summarizes perspectives regarding the development and validation of these models, and discusses how simulation results can be interpreted to facilitate injury risk assessment and head acceleration exposure monitoring in the context of contact sports. Recommendations and consensus statements are presented on the use of validated brain models in conjunction with kinematic sensor data to understand the biomechanics of mTBI and subconcussion. Mainly, there is general consensus that validated brain models have strong potential to improve injury prediction and interpretation of subconcussive kinematic exposure over global head kinematics alone. Nevertheless, a major roadblock to this capability is the lack of sufficient data encompassing different sports, sex, age and other factors. The authors recommend further integration of sensor data and simulations with modern data science techniques to generate large datasets of exposures and predicted brain responses along with associated clinical findings. These efforts are anticipated to help better understand the biomechanical basis of mTBI and improve the effectiveness in monitoring kinematic exposure in contact sports for risk and injury mitigation purposes

Calibration of a heterogeneous brain model using a subject-specific inverse finite element approach

Central to the investigation of the biomechanics of traumatic brain injury (TBI) and the assessment of injury risk from head impact are finite element (FE) models of the human brain. However, many existing FE human brain models have been developed with simplified representations of the parenchyma, which may limit their applicability as an injury prediction tool. Recent advances in neuroimaging techniques and brain biomechanics provide new and necessary experimental data that can improve the biofidelity of FE brain models. In this study, the CAB-20MSym template model was developed, calibrated, and extensively verified. To implement material heterogeneity, a magnetic resonance elastography (MRE) template image was leveraged to define the relative stiffness gradient of the brain model. A multi-stage inverse FE (iFE) approach was used to calibrate the material parameters that defined the underlying non-linear deviatoric response by minimizing the error between model-predicted brain displacements and experimental displacement data. This process involved calibrating the infinitesimal shear modulus of the material using low-severity, low-deformation impact cases and the material non-linearity using high-severity, high-deformation cases from a dataset of in situ brain displacements obtained from cadaveric specimens. To minimize the geometric discrepancy between the FE models used in the iFE calibration and the cadaveric specimens from which the experimental data were obtained, subject-specific models of these cadaveric brain specimens were developed and used in the calibration process. Finally, the calibrated material parameters were extensively verified using independent brain displacement data from 33 rotational head impacts, spanning multiple loading directions (sagittal, coronal, axial), magnitudes (20–40 rad/s), durations (30–60 ms), and severity. Overall, the heterogeneous CAB-20MSym template model demonstrated good biofidelity with a mean overall CORA score of 0.63 ± 0.06 when compared to in situ brain displacement data. Strains predicted by the calibrated model under non-injurious rotational impacts in human volunteers (N = 6) also demonstrated similar biofidelity compared to in vivo measurements obtained from tagged magnetic resonance imaging studies. In addition to serving as an anatomically accurate model for further investigations of TBI biomechanics, the MRE-based framework for implementing material heterogeneity could serve as a foundation for incorporating subject-specific material properties in future models

Investigating Brain Injury Tolerance in the Sagittal Plane Using a Finite Element Model of the Human Head

Despite decades of research and regulation, brain injuries remain a leading cause of traffic related death and disability worldwide. In this study, the human tolerance to brain injury was investigated by applying pure angular and linear kinematic loading conditions in the sagittal plane to a finite element model of the head. The relationship between peak acceleration and impact duration was determined at several levels of constant injury risk for two strain-based injury criteria. Results revealed that brain injury tolerance depends on peak acceleration and impact duration, which were found to be inversely related for constant injury risk

Suitability of enhanced head injury criteria for vehicle rating

Objective: Euro NCAP is considering the implementation of a new head injury assessment with the introduction of THOR in the mobile progressive deformable barrier frontal impact crash test. The objective of this study is to assess the suitability of enhanced head injury criteria for practical application in consumer rating programs. Method: AIS2+ risk predictions from nine selected head injury criteria where calculated for 27 pairs of crash test results representing small and moderate overlap frontal crashes. The capability of each injury criteria to predict the real-world injury rates of these crash modes was evaluated. Next, the correlation coefficients between the head injury candidates were calculated and individual predictions were compared for all tests in scatter plots. Results: The results show that none of the crash tests head injury assessment predicted the four-times higher head injury rates observed in the accident data for small overlap crashes compared to moderate overlap crashes. Poor correlation was demonstrated between many leading brain injury metrics, and the risk predictions for individual vehicles differ quite substantially depending on the criterion considered. Conclusions: While preliminary, the results of this study demonstrate that more evaluation of the most suitable brain injury criteria is necessary before consideration into a consumer evaluation program. Convergence of the head injury criteria risks for individual cases should be part of the validation process for enhanced head injury criteria, since identical head signals should yield similar injury risks