Development of a Multimodal Blast Sensor for Measurement of Head Impact and Over-pressurization Exposure

It is estimated that 10–20% of United States soldiers returning from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) have suffered at least one instance of blast-induced traumatic brain injury (bTBI) with many reporting persistent symptomology and long-term effects. This variation in blast response may be related to the complexity of blast waves and the many mechanisms of injury, including over-pressurization due to the shock wave and potential for blunt impacts to the head from shrapnel or from other indirect impacts (e.g., building, ground, and vehicle). To help differentiate the effects of primary, secondary, and tertiary effects of blast, a custom sensor was developed to simultaneously measure over-pressurization and blunt impact. Moreover, a custom, complementary filter was designed to differentiate the measurements of blunt (low-frequency bandwidth) from over-pressurization (high-frequency bandwidth). The custom sensor was evaluated in the laboratory using a shock tube to simulate shock waves and a drop fixture to simulate head impacts. Both bare sensors and sensor embedded within an ACH helmet coupon were compared to laboratory reference transducers under multiple loading conditions (n = 5) and trials at each condition (n = 3). For all comparative measures, peak magnitude, peak impulse, and cross-correlation measures, R ² values, were greater than 0.900 indicating excellent agreement of peak measurements and time-series comparisons with laboratory measures.     

Brain Injuries from Blast

Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is appropriate between species, many reported rodent blast TBI experiments using air shock tubes have blast overpressure conditions that are similar to human long-duration nuclear blasts, not high explosive blasts.     

Altered gene expression in cultured microglia in response to simulated blast overpressure: Possible role of pulse duration

Blast overpressure has long been known to cause barotrauma to air-filled organs such as lung and middle ear. However, experience in Iraq and Afghanistan is revealing that individuals exposed to explosive munitions can also suffer traumatic brain injury (TBI) even in the absence of obvious external injury. The interaction of a blast shock wave with the brain in the intact cranial vault is extremely complex making it difficult to conclude that a blast wave interacts in a direct manner with the brain to cause injury. In an attempt to “isolate” the shock wave and test its primary effects on cells, we exposed cultured microglia to simulated blast overpressure in a barochamber. Overpressures ranging from 15 to 45 psi did not change microglial Cox-2 levels or TNF-α secretion nor did they cause cell damage. Microarray analysis revealed increases in expression of a number of microglial genes relating to immune function and inflammatory responses to include Saa3, Irg1, Fas and CxCl10. All changes in gene expression were dependent on pulse duration and were independent of pressure. These results indicate that microglia are mildly activated by blast overpressure and uncover a heretofore undocumented role for pulse duration in this process.     

Development of a Finite Element Model for Blast Brain Injury and the Effects of CSF Cavitation

Blast-related traumatic brain injury is the most prevalent injury for combat personnel seen in the current conflicts in Iraq and Afghanistan, yet as a research community,we still do not fully understand the detailed etiology and pathology of this injury. Finite element (FE) modeling is well suited for studying the mechanical response of the head and brain to blast loading. This paper details the development of a FE head and brain model for blast simulation by examining both the dilatational and deviatoric response of the brain as potential injury mechanisms. The levels of blast exposure simulated ranged from 50 to 1000 kPa peak incident overpressure and 1–8 ms in positive-phase duration, and were comparable to real-world blast events. The frontal portion of the brain had the highest pressures corresponding to the location of initial impact, and peak pressure attenuated by 40–60% as the wave propagated from the frontal to the occipital lobe. Predicted brain pressures were primarily dependent on the peak overpressure of the impinging blast wave, and the highest predicted brain pressures were 30%less than the reflected pressure at the surface of blast impact. Predicted shear strain was highest at the interface between the brain and the CSF. Strain magnitude was largely dependent on the impulse of the blast, and primarily caused by the radial coupling between the brain and deforming skull.The largest predicted strains were generally less than 10%,and occurred after the shock wave passed through the head.For blasts with high impulses, CSF cavitation had a large role in increasing strain levels in the cerebral cortex and periventricular tissues by decoupling the brain from the skull. Relating the results of this study with recent experimental blast testing suggest that a rate-dependent strain-based tissue injury mechanism is the source primary blast TBI.     

A thoracic mechanism of mild traumatic brain injury due to blast pressure waves

The mechanisms by which blast pressure waves cause mild-to-moderate traumatic brain injury (mTBI) are an open question. Possibilities include acceleration of the head, direct passage of the blast wave via the cranium, and propagation of the blast wave to the brain via a thoracic mechanism. The hypothesis that the blast pressure wave reaches the brain via a thoracic mechanism is considered in light of ballistic and blast pressure wave research. Ballistic pressure waves, caused by penetrating ballistic projectiles or ballistic impacts to body armor, can only reach the brain via an internal mechanism and have been shown to cause cerebral effects. Similar effects have been documented when a blast pressure wave has been applied to the whole body or focused on the thorax in animal models. While vagotomy reduces apnea and bradycardia due to ballistic or blast pressure waves, it does not eliminate neural damage in the brain, suggesting that the pressure wave directly affects the brain cells via a thoracic mechanism. An experiment is proposed which isolates the thoracic mechanism from cranial mechanisms of mTBI due to blast wave exposure. Results have implications for evaluating risk of mTBI due to blast exposure and for developing effective protection.     

Biomechanical Assessment of Brain Dynamic Responses Due to Blast Pressure Waves

A mechanized and integrated computational scheme is introduced to determine the human brain responses in an environment where the human head is exposed to explosions from trinitrotoluene (TNT), or other high-yield explosives, in military applications. The procedure is based on a three-dimensional (3-D) non-linear finite element method (FEM) that implements a simultaneous conduction of explosive detonation, shock wave propagation, blast–head interactions, and the confronting human head. The processes of blast propagation in the air and blast interaction with the head are modeled by an Arbitrary Lagrangian–Eulerian (ALE) multi-material FEM formulation, together with a penalty-based fluid/structure interaction (FSI) algorithm. Such a model has already been successfully validated against experimental data regarding air-free blast and plate–blast interactions. The human head model is a 3-D geometrically realistic configuration that has been previously validated against the brain intracranial pressure (ICP), as well as shear and principal strains under different impact loadings of cadaveric experimental tests of Hardy et al. [Hardy W. N., C. Foster, M. Mason, S. Chirag, J. Bishop, M. Bey, W. Anderst, and S. Tashman. A study of the response of the human cadaver head to impact. Proc. 51 ^st Stapp. Car Crash J. 17–80, 2007]. Different scenarios have been assumed to capture an appropriate picture of the brain response at a constant stand-off distance of nearly 80 cm from the core of the explosion, but exposed to different amounts of a highly explosive (HE) material such as TNT. The overpressures at the vicinity of the head are in the range of about 2.4–8.7 atmosphere (atm), considering the reflected pressure from the head. The methodology provides brain ICP, maximum shear stresses and maximum principal strain within the milli-scale time frame of this highly dynamic phenomenon. While focusing on the two mechanical parameters of pressure, and also on the maximum shear stress and maximum principal strain to predict the brain injury, the research provides an assessment of the brain responses to different amounts of overpressure. The research also demonstrates the ability to predict the ICP, as well as the stress and strain within the brain, due to such an event. The research cannot identify, however, the specific levels of ICP, stress and strain that necessarily lead to traumatic brain injury (TBI) because there is no access to experimental data regarding head–blast interactions.     

Mild traumatic brain injury and posttraumatic stress disorder in returning veterans: Perspectives from cognitive neuroscience

A significant proportion of military personnel deployed in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has been exposed to war-zone events potentially associated with traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). There has been significant controversy regarding healthcare policy for those service members and military veterans who returned from OEF/OIF deployments with both mild TBI and PTSD. There is currently little empirical evidence available to address these controversies. This review uses a cognitive neuroscience framework to address the potential impact of mild TBI on the development, course, and clinical management of PTSD. The field would benefit from research efforts that take into consideration the potential differential impact of mild TBI with versus without persistent cognitive deficits, longitudinal work examining the trajectory of PTSD symptoms when index trauma events involve TBI, randomized clinical trials designed to examine the impact of mild TBI on response to existing PTSD treatment interventions, and development and examination of potential treatment augmentation strategies.     

Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model

Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.     

Skull Flexure as a Contributing Factor in the Mechanism of Injury in the Rat when Exposed to a Shock Wave

The manner in which energy from an explosion is transmitted into the brain is currently a highly debated topic within the blast injury community. This study was conducted to investigate the injury biomechanics causing blast-related neurotrauma in the rat. Biomechanical responses of the rat head under shock wave loading were measured using strain gauges on the skull surface and a fiber optic pressure sensor placed within the cortex. MicroCT imaging techniques were applied to quantify skull bone thickness. The strain gauge results indicated that the response of the rat skull is dependent on the intensity of the incident shock wave; greater intensity shock waves cause greater deflections of the skull. The intracranial pressure (ICP) sensors indicated that the peak pressure developed within the brain was greater than the peak side-on external pressure and correlated with surface strain. The bone plates between the lambda, bregma, and midline sutures are probable regions for the greatest flexure to occur. The data provides evidence that skull flexure is a likely candidate for the development of ICP gradients within the rat brain. This dependency of transmitted stress on particular skull dynamics for a given species should be considered by those investigating blast-related neurotrauma using animal models.     

Distribution of Blood–Brain Barrier Disruption in Primary Blast Injury

Traumatic brain injury (TBI) resulting from explosive-related blast overpressure is a topic at the forefront of neurotrauma research. Compromise of the blood–brain barrier (BBB) and other cerebral blood vessel dysfunction is commonly reported in both experimental and clinical studies on blast injury. This study used a rifle primer-driven shock tube to investigate cerebrovascular injury in rats exposed to low-impulse, pure primary blast at three levels of overpressure (145, 232, and 323 kPa) and with three survival times (acute, 24, and 48 h). BBB disruption was quantified immunohistochemically by measuring immunoglobulin G (IgG) extravasation with image analysis techniques. Pure primary blast generated small lesions scattered throughout the brain. The number and size of lesions increased with peak overpressure level, but no significant difference was seen between survival times. Despite laterally directed blast exposure, equal numbers of lesions were found in each hemisphere of the brain. These observations suggest that cerebrovascular injury due to primary blast is distinct from that associated with conventional TBI.     

Revealing the Effect of Skull Deformation on Intracranial Pressure Variation During the Direct Interaction Between Blast Wave and Surrogate Head

Annals of Biomedical Engineering - Intracranial pressure (ICP) during the interaction between blast wave and the head is a crucial evaluation criterion for blast-induced traumatic brain injury...     

狗冲击伤的荷载机制及效应研究

本文通过对暴露于空中爆炸波(激波)中的动物所承受不同的激波压力模态进行分析,表明处于规则反射区(NRA)与马赫反射区(MRA)中的动物的荷载机制是明显不同的。有关动物的实验结果是采用BST—Ⅰ型生物激波管致伤。其一选用44只雄性杂种狗是有端板(即NRA或MRA有反射壁)状态,另外选用8只雄性杂种狗是开口(即MRA自由场)状态。两组实验表明其创伤严重特点和创伤的分布规律都存在显著的差异。所观察到的各个器官的病理形态学和超微结构改变的动物实验结果,能够为冲击伤防护和诊治的进一步研究提供理论和临床上的依据。     

爆炸冲击波在生物体内的传播特征

目的：了解爆炸冲击波在生物体内的传播特征。材料方法：采用压力测试方法,研究爆炸冲击波在肝、肺、血管及皮下组织内的传播特征,并与空气中的传播特征进行比较。结果：爆炸冲击波在不同介质中的衰减速度依次为：空气＞皮下组织＞血液;不同部位对爆炸冲击波感应的敏感度依次为：颅脑＞胸腔＞肝脏;颅脑内的应力感应方式不同于其他部位,以骨性震动传导为主要特征。结论：研究结果为体外模拟研究及为爆炸性冲击伤的诊断治疗提供了理论依据。     

Methodology and Evaluation of Intracranial Pressure Response in Rats Exposed to Complex Shock Waves

Studies on blast neurotrauma have focused on investigating the effects of exposure to free-field blast representing the simplest form of blast threat scenario without considering any reflecting surfaces. However, in reality personnel are often located within enclosures or nearby reflecting walls causing a complex blast environment, that is, involving shock reflections and/or compound waves from different directions. The purpose of this study was to design a complex wave testing system and perform a preliminary investigation of the intracranial pressure (ICP) response of rats exposed to a complex blast wave environment (CBWE). The effects of head orientation in the same environment were also explored. Furthermore, since it is hypothesized that exposure to a CBWE would be more injurious as compared to a free-field blast wave environment (FFBWE), a histological comparison of hippocampal injury (cleaved caspase-3 and glial fibrillary acidic protein (GFAP)) was conducted in both environments. Results demonstrated that, regardless of orientation, peak ICP values were significantly elevated over the peak static air overpressure. Qualitative differences could be noticed compared to the ICP response in rats exposed to simulated FFBWE. In the CBWE scenario, after the initial loading the skull/brain system was not allowed to return to rest and was loaded again reaching high ICP values. Furthermore, results indicated consistent and distinct ICP-time profiles according to orientation, as well as distinctive values of impulse associated with each orientation. Histologically, cleaved caspase-3 positive cells were significantly increased in the CBWE as compared to the FFBWE. Overall, these findings suggest that the geometry of the skull and the way sutures are distributed in the rats are responsible for the difference in the stresses observed. Moreover, this increase stress contributes to correlation of increased injury in the CBWE.     

水下爆炸性冲击波实验模型的建立及其应力分布特性的研究

目的：建立水下爆炸性冲击波实验模型并分析其应力分布特性。方法：根据爆炸性冲击波的理论应力分布特性，建立水下爆炸性冲击波实验模型，将培养的内皮细胞放入特制的无菌薄层塑料袋内模拟细胞致伤模型，用80mg电雷管致伤后[观察细胞损伤情况。结果：爆炸性冲击波在水中的衰减速度较空气中缓慢，水的深度对冲击波压力峰值有显著影响，对于同一爆源，水越深，压力值越小，不同层数的滤膜覆盖与压力感应呈线性衰减，8层滤膜覆盖致伤时可见内皮细胞有明显的皱缩脱落现象。结论：冲击波在不同介质中的传播速度与衰减幅度与介质的密度密切相关，水下冲击波的压力值不仅与焊源的距离有关，而且与水深有关。     

面部碰撞对行人创伤性脑损伤影响的生物力学研究

为预测和评判行人面部碰撞对创伤性脑损伤机理及生物力学响应,结合计算机断层扫描（CT）和磁共振（MRI）医学成像技术,建立符合中国人体特征的50百分位头颈部几何模型和有限元模型。有限元模型中颅骨与脑之间的相对运动采用切向滑动边界条件,摩擦系数定义为0.2,模拟鼻骨斜碰撞、鼻外侧软骨正面碰撞、牙齿正面碰撞、下颌骨碰撞和颧骨外侧斜碰撞等5种典型面部碰撞交通事故场景,探讨应力波在颅骨和脑内传播路径,得到颅内压力、von Mises等效应力和剪切应力等生物力学响应参数分布规律。结果显示,鼻骨斜碰撞颅内压力峰值为236.7 kPa,von Mises应力为25.97 kPa,超过了大脑耐受阈值;颧骨外侧斜碰撞最大横向剪切应力分别为14.56 kPa和-18.07 kPa,促使脑组织产生了较大的剪切变形,存在严重脑损伤风险。结论表明：面部碰撞的位置和方向是导致面部骨折严重程度的关键因素,面骨骨折的位置决定创伤性脑损伤的部位,面骨骨折都带有一定程度的创伤性脑损伤;头部受到冲击时,面部结构能够吸收大量的冲击能量来保护大脑,降低颅脑损伤的风险。     

Up-regulation of reactivity and survival genes in astrocytes after exposure to short duration overpressure

Gurdjian et al. proposed decades ago that pressure gradients played a major factor in neuronal injury due to impact. In the late 1950s, their experiments on concussion demonstrated that the principal factor in the production of concussion in animals was the sudden increase of intracranial pressure accompanying head injury. They reported the increase in pressure severity correlated with an increase in 'altered cells' resulting in animal death. More recently, Hardy et al. (2006) demonstrated the presence of transient pressure pulses with impact conditions. These studies indicate that short duration overpressure should be further examined as a mechanism of traumatic brain injury (TBI). In the present study, we designed and fabricated a barochamber that simulated overpressure noted in various head injury studies. We tested the effect of overpressure on astrocytes. Expressions of apoptotic, reactivity and survival genes were examined at 24, 48 and 72 h post-overpressure exposure. At 24 h, we found elevated levels of reactivity and survival gene expression. By 48 h, a decreased expression of apoptotic genes was demonstrated. This study reinforces the hypothesis that transient pressure acts to instigate the cellular response displayed following TBI.     

冲击伤对大鼠条件性回避反应习得和保持的影响

实验用Wistar大鼠26只,分为冲击波全身致伤组(Ⅰ组),冲击波头部致伤组(Ⅱ组)和对照组。以条件性回避反应(conditioned avoidance response,CAR)作为学习和记忆的指标,观察BST系列生物激波管产生的冲击波对CAR的影响。结果如下:(1)Ⅰ组和Ⅱ组大鼠的CAR习得率在伤后5天内均明显低于对照组(P<0.05),尤以Ⅱ组大鼠的降低更为显著(P<0.01);(2)自伤后第5天起CAR习得率便逐渐升高,至第10天时已接近对照组水平(P<0.05);(3)Ⅱ组动物CAR的保持显著低于对照组(P<0.01),而Ⅰ组仅有一过性的降低。以上结果显示,大鼠学习和记忆能力的降低主要是由于冲击波直接作用于头部的结果,但不能排除肺损伤后引起神经系统的损害。     

兔胸腹部爆炸伤后的血液浓缩及其可能机制

目的 :探讨爆炸性冲击伤后血液浓缩的特点及其可能的机制。方法 :采用雷管所致兔爆炸性冲击损伤模型 ,以1 2 5I 白蛋白标记的方法 ,观察爆炸性冲击伤前后红细胞压积与血浆外渗情况。结果 :距爆源 2 0cm处的爆炸冲击波作用时 ,红细胞压积增加 14 .9% ,血浆丢失为对照的 5 .12倍 ,白蛋白漏出率为伤前的 1.3倍 ,左肺组织中残留放射性较对照组增加约 18% ,该点平均压力峰值为 174 .4kPa。结论 :爆炸冲击伤后的红细胞压积增加、血浆丢失是伤后微循环功能障碍的重要原因     

Brain oscillatory 4-35 Hz EEG responses during an n-back task with complex visual stimuli

Acetylcholinesterase (AChE) which catalyzes the hydrolysis of the neurotransmitter acetylcholine has been recognized as one of the major regulators of stress responses after traumatic brain injury (TBI). Repeated blast exposure induces TBI (blast TBI) with a variable neuropathology at different brain regions. Since AChE inhibitors are being used as a line of treatment for TBI, we sought to determine the time course of AChE activity in the blood and different brain regions after repeated blast exposures using modified Ellman assay. Our data showed that repeated blast exposures significantly reduced AChE activity in the whole-blood and erythrocytes by 3-6 h, while plasma AChE activity was significantly increased by 3 h post-blast. In the brain, significant increase in AChE activity was observed at 6 h in the frontal cortex, while hind cortex and hippocampus showed a significant decrease at 6 h post-blast, which returned to normal levels by 7 days. AChE activity in the cerebellum and mid brain showed a decrease at 6 h, followed by significant increase at 3 days and that was decreased significantly at 14 days post-blast. Medulla region showed decreased AChE activity at 24 h post-blast, which was significantly increased at 14 days. These results suggest that there are brain regional and time-related changes in AChE activity after tightly coupled repeated blast exposures in mice. In summary, acute and chronic regional specific changes in the AChE activity after repeated blast exposures warrant systematic evaluation of the possibility of AChE inhibitor therapeutics against blast TBI.