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Biophysical Mechanisms of Traumatic Brain Injuries Gregory T. Rule, MS2
Robert T. Bocchieri, PhD3
1 Physical Security and Applied Sciences Sector, Applied Research
Associates Inc., Dallas, Texas 2 Physical Security and Applied Sciences Sector, Applied Research Associates, Inc., San Antonio, Texas 3 Silicon Valley Office, Applied Research Associates, Inc., Los Altos, California
Jennie M. Burns, PhD2
Address for correspondence Lee Ann Young, BS, MA, Physical Security and Applied Sciences Sector, Applied Research Associates Inc, 13915 Preston Valley Pl, Dallas, TX 75240 (e-mail: [email protected]).
Semin Neurol 2015;35:5–11.
Abstract
Keywords
► ► ► ► ► ► ►
traumatic brain injury blunt trauma blast ballistic physics acceleration diffuse axonal injury
Despite years of effort to prevent traumatic brain injuries (TBIs), the occurrence of TBI in the United States alone has reached epidemic proportions. When an external force is applied to the head, it is converted into stresses that must be absorbed into the brain or redirected by a helmet or other protective equipment. Complex interactions of the head, neck, and jaw kinematics result in strains in the brain. Even relatively mild mechanical trauma to these tissues can initiate a neurochemical cascade that leads to TBI. Civilians and warfighters can experience head injuries in both combat and noncombat situations from a variety of threats, including ballistic and blunt impact, acceleration, and blast. It is critical to understand the physics created by these threats to develop meaningful improvements to clinical care, injury prevention, and mitigation. Here the authors review the current state of understanding of the complex loading conditions that lead to TBI and characterize how these loads are transmitted through soft tissue, the skull and into the brain, resulting in TBI. In addition, gaps in knowledge and injury thresholds are reviewed, as these must be addressed to better design strategies that reduce TBI incidence and severity.
The occurrence of traumatic brain injury (TBI) in the United States has reached epidemic proportions. The Center of Disease Control (CDC) reports that there are 2.2 million TBIs each year in the United States, including 50,000 fatalities and 280,000 hospitalizations. Traumatic brain injury accounts for 30% of injuries resulting in death in the United States.1 Within the military, TBI statistics vary widely due to the difficulties associated with diagnosing mild TBI2; however, reports indicate that up to 20% of returning veterans from Afghanistan and Iraq have head injuries.3 Although many individuals recover function in the months following TBI, others continue to experience chronic symptoms of cognitive, emotional, and physical impairment for months or years.4,5 Here we review the specific biophysical mechanisms of TBI associated with blunt, penetrating, and blast impact to the head. For each, we describe the physics of the interaction
Issue Theme Traumatic Brain Injury; Guest Editor, Geoffrey Ling, MD, PhD, FAAN, FANA
between the insult and the head, and discuss a summary of the state of the science with respect to injury thresholds.
Causes of Traumatic Brain Injury Traumatic brain injury is caused by a blunt, penetrating, or blast impact to the head. Key mechanisms by which energy may mechanically transfer into the skull and brain from external sources include direct impact by a solid object (blunt or penetrating impact) or fluid shock wave (blast impact), and rapid linear and/or rotational acceleration of the head, resulting in material stresses and strains. The direct impact of the head with a solid object may result in either a blunt or penetrating injury, with the type of injury dependent upon the mass, speed, and cross-sectional area of the object in comparison to the head.
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0035-1544242. ISSN 0271-8235.
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Lee Ann Young, BS, MA1
Biophysical Mechanisms of Traumatic Brain Injuries
Young et al.
Blunt Impact Blunt-impact head wounds are caused by objects that are usually of low velocity, high mass, and high cross-sectional area. Blunt impact to the head may cause lacerations and contusions on the scalp, localized deformation of the skull, coup/contrecoup impact (impact of the brain with the inner walls of the skull) caused by the rapid linear and/or rotational acceleration/deacceleration of the head, and increased intracranial pressure (ICP) gradients.6 The deformation of the skull transmits localized stress to the underlying tissues resulting in strains to the neural and neurovascular tissue. The rebound of the skull from deformation can cause a separation in the dura mater and skull, resulting in epidural hematomas.7 Contusions are often found at the coup and contrecoup sites of impact. Intracranial pressure gradients are generated by the inertia of the brain during head motion; when the brain lags behind the skull during linear acceleration, it “pushes” against the skull causing a pressure increase at the point of loading and a pressure decrease (negative pressure) distally to that point.7 Axons are stretched as a result of the shear stresses and strains caused by the gross motion of the brain inside the skull and these ICP gradients, leading to diffuse axonal injuries (DAIs) characterized by an enlargement of the axons at the locations where the microtubules are damaged.8 Rapid linear or rotational acceleration of the head may alone, without the impact of the head with a foreign object, cause coup/contrecoup injury. There are two theories regarding how rapid head acceleration results in brain injury. The first theory proposes that the brain is unable to rotate within the skull at the same velocity as the surrounding skull, leading to focal shear stresses and strains.6 Because the skull is most constraining in the frontal compartments and around the foramen magnum, this theory predicts a concentration of injuries near these locations, and in fact literature shows that there is a predominance of anterior fossa injuries regardless of whether the impact is frontal or occipital.9 The second theory proposes that diffuse shearing of brain tissues occurs at sites where adjacent tissues have sufficiently different densities to result in different rates of motion.10 Research into the diffuse injuries caused by rotation show that the damaging strains through inertial loading are greatest near the surface of the brain and decrease toward the center,11 such that low levels of rotational inertial loading affect only the cortex, and only the more severe loads result in damage down into the diencephalon.6 Animal models and numerical models have shown that DAI, acute subdural hematoma, and most other types of brain injury can be generated purely by rotational motion.12–15 However, more recently, the dominant consensus is that brain injuries result from a combination of translational motion, leading to direct site contusions and ICP, and rotational motion, leading to shear strains.16 Coup and contrecoup injuries appear to be pressure induced, and brainstem injuries appear to be associated with shear strain.17
Penetrating Impact Penetrating head wounds are caused by high-velocity objects, such as bullets or fragments, combined with low mass and Seminars in Neurology
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low cross-sectional area, or low-velocity knives and comparably higher mass and lower cross-sectional area. Penetrating objects of low velocity will cause lacerations on the scalp, fractures of the skull, and destruction or injury to the brain tissue in the immediate path of the penetrating object. For penetrating objects of sufficiently high velocity, there is an additional risk of increased ICP from a temporary cavity formed around the penetrating object. These high ICPs within the confines of the skull may cause the respiratory and cardiac centers of the medulla to fail, resulting in immediate death.16 For knife wounds or gunshot wounds, where most of the energy of the object is expended during penetration of the skull, there may only be localized damage and the patient may remain conscious. If the projectile or fragments of the skull remains inside the cranial cavity, these patients could be good candidates for débridement and survival is possible. If there is no penetration, but a fracture of the skull occurs, the patient may remain conscious, but could still be in danger of a subsequent increase in ICP from an epidural, subdural, and or subarachnoid hematoma.18,19
Blast Impact The environment in and around a blast is complex. For an exhaustive overview of blast physics, including shock and blast wave generation, Mach stem formation, and the physics of explosions, there are numerous sources that provide thorough descriptions.20,21 Individuals exposed to blast may be exposed to multiple, concurrent effects of blast such as thermal heating, ballistic impact from shrapnel and fragments, blunt impact, and acceleration from falling or striking walls and large displaced masses, and impact with fluid shock waves (blast overpressure) and acoustic waves, and in nuclear explosions, radiation. Exposure to blast overpressure alone can result in primary TBI caused by the direct impact of the shock against the head, direct transmission of blast wave energy through the head into the brain, and short duration accelerative motions of the head caused by temporal gradients in overpressure around the surface of the head. Like any potentially injurious loading environment, blast exposure establishes a transfer of energy from the external environment into the head. This transfer of energy ultimately results in tissue damage through several proposed underlying mechanisms, most of which have only limited validation in experimental data. These mechanisms include, but are not limited to, formation of air emboli or surges of fluid in the brain induced by thoracic pressure,22–24 shear and stress waves inducing micro (cellular and subcellular)25 and macro (gross morphological) level damage,26 physical deformation or flexing of the skull caused by pressure gradients,27 cerebrospinal fluid cavitation,28–30 and acceleration of the brain against the inside of the skull.31 To understand how blast waves may cause TBI, a fundamental understanding of how energy is deposited in the brain is required. The profile of the blast wave (e.g., number, magnitude, and duration of the blast overpressure peaks) is dependent on the characteristics of the explosive materials (e.g., dynamite [TNT] vs. improvised explosive device [IEDs]), the material in which the explosive is housed (e.g., metal
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contrecoup regions are shown to be more exposed to high magnitude pressures, and consequently greater injury, due to the reflection of the shock wave at the interface of the brain with the skull.42
Thresholds of TBI Blunt Impact and Acceleration The most commonly used criterion for ascertaining whether the head will sustain an injury caused by blunt impact or acceleration is the Head Injury Criterion (HIC).43 The HIC was proposed in 1970 based on the experimental results of 23 drop tests using five embalmed cadaver heads conducted in the late 1950s.44 The equation to calculate the HIC is shown in Equation 1:
where t1 is the initial time (s), t2 is the final time (s), and a(t) is the acceleration (g) at the center of gravity of the head. The acceleration window (t2–t1) is usually 15 milliseconds (ms) or 36 ms, depending upon the context of the impact (for automotive applications, it is usually 15 ms). This criterion is primarily used to design protective measures for automobiles. The Federal Motor Vehicle Safety Standard (FMVSS) 208 (occupant crash protection) and FMVSS-213 (child restraint systems) use a HIC of 1,000 as the threshold for head injury characterized by skull fracture or subdural hematomas. A head-injury risk curve was developed by Prasad and Mertz45 using postmortem human subjects to determine the relationship between the HIC and the probability of sustaining a lifethreatening injury. Based upon their data, a HIC of 1,400 gives a probability of sustaining a life-threatening brain injury of 0.5 and a HIC of 1,000 puts the probability at 0.18.46 The other injury criterion commonly used is the 150-g peak acceleration criterion. This criterion was based upon accident data from U.S. Army aviation accidents,47,48 and developed from experiments with the International Standards Organization (ISO) head form; like the HIC, following this criterion in the design of protective equipment can prevent skull fracture and subdural hematoma.
Fig. 1 Computational simulation of the exposure of a soldier to blast showing the profile of the peak overpressures across the surface of the entire body. (Wiri S, Needham C. Reconstruction of IED blast loading to personnel in the open. Paper presented at: 21st International Shock Interaction Symposium, International Shock Wave Institute; August 3–8, 2014; Riga, Latvia). Seminars in Neurology
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casing, air, or soil), the presence of reflecting objects near the exposed individual, the position and orientation of the individual to the blast, the stature and shape of the individual resulting in varying exposed cross-sectional areas of the body, and the use of protective equipment (e.g., Kevlar vests, helmets, etc.).32,33 Thus, each blast scenario can result in the exposure of an individual to a unique pressure wave profile and a unique deposition of energy into the brain resulting in a unique injury. As seen in ►Fig. 1, pressures across the head and body can vary widely. The pressure variations determine how energy affects the body in terms of implied forces, which can induce accelerations even without direct impact. In this scenario, the soldier experienced extremely high pressures on the shoulder and arm, which may have minimal physiological effect; however, exposures to the left ear exceeded 8 psi, which is sufficient to rupture the tympanic membrane.34 At higher pressure levels, from a larger blast or a smaller standoff distance, the pressure differentials across the head could cause both head deformation27 and acceleration.35 Ultimately, exposure to blast results in neuronal damage and tissue disruption, often detected in the traditional coup and contrecoup regions, and diffuse axonal injuries caused by induced stress and strains within the living tissues of the brain.36 Because these stresses and strains cannot be directly measured, measurement of ICP can provide a useful surrogate method for estimating energy deposition, particularly because ICPs have shown to correlate with fatality rates.37 In addition, computational modeling can provide significant insight into transmission and dissipation of blast energy through and into the brain tissue. Several computational models validated against both live and cadaver animal tests have shown that the skull generally behaves as a low-pass filter by which the higher frequencies are removed as the blast wave passes through the calvarium.38–41 Based upon these simulations, stress waves induce shear, spallation, implosion, and inertial effects within the brain tissue.33 Computational models have also shown that peak stresses and strains within the brain correlate with high-pressure regions at the coup and contrecoup locations30,36; the coup/
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Penetrating Impact
Discussion
Setting a single injury threshold for penetration injury is challenging due to the interrelationship between the velocity, mass, shape, and diameter of the projectile. The majority of the studies investigating trauma to all regions of the body use gelatin as the simulant for injury/wound quantification. 49 For studies investigating penetrating injury to the head, projectiles are fired into a rectangularshaped simulant without any backing material to approximate the skull, which is an inappropriate means to study the biomechanics of TBI. One study conducted by Yoganandan poured silicone dielectric gel (Sylgard 527; Dow Corning, Midland, MI) and ballistic gelatin into a sphere that approximated the skull. 50 The study used two different projectiles (9 mm and 25 caliber) to determine the formation and collapse of the temporary cavity inside the sphere and the pressures generated. Because the Sylgard gel has material properties closer to that of the human brain, Yoganandan claimed the gel was a more appropriate simulant for the study of penetrating brain injuries. Pressure distributions from experimental studies such as these can be used to validate future models for determining brain injury thresholds. Although no single injury threshold for the head exists, it is widely believed that any skull penetration from a high-velocity projectile is likely to cause instantaneous physiological incapacitation with a high likelihood of long-term disability or death.51 For this reason, all ballistic head protection is designed to a zeropenetration criterion, leaving behind-armor blunt trauma as the major risk of injury from ballistic threats because ballistic helmets are allowed to deform. The NIJ (National Institute of Justice) standard for ballistic helmets requires that backface deformation be no more than 16 mm for crown left and right impacts and no more than 25.4 mm for front and rear impacts, but there is no scientific basis to link these values to brain injury.52
Blast Impact There are no established injury criteria for blast-induced brain injury. Several efforts have been focused on developing criteria for brain injury using a variety of outcomes ranging from apnea37 to fatality.39 Recently, computational modeling, validated against available test data, has provided a first estimate for blast-induced brain injury criteria based on the occurrence of apnea immediately following blast exposure.53 In addition, the 150-g peak acceleration criterion and the HIC are the only criteria available to estimate the risk of head injury from accelerative motion. Unfortunately, these criteria only apply to gross accelerative motion in excess of 15 ms in duration; both modeling and testing has demonstrated that blast exposures of 30 to 40 psi peak overpressure can induce short duration, from < 1 to 6 to 7 ms, accelerations in excess of 400 g.54 Furthermore, criteria based on data from traditional blunt impact tests are likely not applicable to the blast impact as the mechanics involved are different, thus rendering conclusions based upon these criteria for blast-induced neurotrauma highly questionable. Seminars in Neurology
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Because experiments to investigate the threshold of TBI using live humans are unethical, research approaches to studying TBI have been limited to prospective or retrospective studies on people who are likely to develop TBI (e.g., athletes or veterans returning from war) or have been diagnosed with TBI (e.g., survivors of automobile collisions or terrorist attacks), or experimental testing on cadavers and animals. Accurate information regarding the biomechanical insult is difficult to obtain in most prospective studies and virtually all retrospective studies. The validity of cadaver tests is limited by the lack of muscle activation and physiological responses, and the validity of animal tests is limited by the anatomical and functional differences of the brain between species. Given these limitations, injury criteria and thresholds are based on indirect measures and global rigid-body kinematics. As a result, we have a limited understanding of the specific biomechanical processes that lead to TBI. The criteria used to define the threshold for injury caused by blunt impact to the head, the HIC and the 150g criteria, are sufficient for evaluating helmets in protection against skull fracture and hematoma; however, there are no criteria for the other types of brain injuries (e.g., cognitive dysfunction caused by neurochemical cascades) that can occur from blunt impact or rapid acceleration. Intense research into football-related impacts has attempted to correlate external accelerations with internal brain stresses using computer simulations,31,55–57 head surrogates, and real-time collection of acceleration data. Ongoing data collections with collegiate football teams 58 and upcoming joint Department of Defense and National Football League data collection efforts provide opportunities to collect massive amounts of data that have the potential to provide valuable insights into the threshold loads. However, both of these efforts are impeded by ambiguity in the definition and diagnosis of mild TBI, which makes it difficult to correlate measures of loads (pressures, forces, or impulses) in these databases to consistent levels of injury, particularly when the susceptibility of the brain to injury changes with repeated impacts.59 Additionally, these studies are challenged by the lack of subjects who are naïve to concussion, presenting a confounding factor of potential induced vulnerability.60 The primary challenge with respect to blast-induced TBI is the remaining uncertainty regarding injury mechanisms. Although many mechanisms have been proposed, inconsistencies in test methods, including exposure levels, approaches to blast generation and measures of effect, have resulted in confusing and sometimes conflicting results. One of the most significant experimental issues has been replication of blast environments in a laboratory setting. Shock tubes have proliferated in the last decade of blast neurotrauma research; however, many tubes are used incorrectly, placing the test specimen downstream of the shock tube exit (i.e., in front of the tube), rather than inside it. Because the shock wave rapidly expands outside the tube
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Conclusion Research to determine the dose–response curves or thresholds of TBI remain important in developing safer protective equipment and minimizing the risk of neurotrauma for both the civilian and military communities. For ballistic and penetrating impact neurotrauma, physiological-based behindhelmet blunt trauma criteria are needed. For blunt impact neurotrauma, criteria are needed for mild and moderate closed-head injuries, such as rapid linear or rotational acceleration, that do not involve skull fractures or subdural hematomas. For blast and to a lesser extent, blunt impact-caused neurotrauma, the greatest need continues to be clarity on the mechanisms of injury so that we can develop valid injury criteria in animal models and scale those criteria to humans. Investigation into the mechanisms of TBI will ultimately improve our ability to prevent, diagnose, and treat this debilitating disease.
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References 1 Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the
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4 5 6 7
8
9 10
11 12
13
14
15
16
17
18
19
20 21
United States emergency department visits, hospitalizations, and deaths. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010 Levine B, Schweizer TA, O’Connor C, et al. Rehabilitation of executive functioning in patients with frontal lobe brain damage with goal management training. Front Hum Neurosci 2011;5:9 Theeler BJ, Flynn FG, Erickson JC. Headaches after concussion in US soldiers returning from Iraq or Afghanistan. Headache 2010;50(8): 1262–1272 Kraus JF, McArthur DL, Silberman TA. Epidemiology of mild brain injury. Semin Neurol 1994;14(1):1–7 Kraus JF, Nourjah P. The epidemiology of mild, uncomplicated brain injury. J Trauma 1988;28(12):1637–1643 Post A, Hoshizaki TB. Mechanisms of brain impact injuries and their prediction: a review. J Trauma 2012;14(4):327–349 Gurdjian ES. Re-evaluation of the biomechanics of blunt impact injury of the head. Surg Gynecol Obstet 1975;140(6): 845–850 King AI. Fundamentals of impact biomechanics: Part I—biomechanics of the head, neck, and thorax. Annu Rev Biomed Eng 2000; 2:55–81 Hardy WN, Khalil TB, King AI. Literature review of head injury biomechanics. Int J Impact 1994;15(4):561–586 Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations of blunt head injuries. Brain 1974;97(4):633–654 Ommaya AK, Thibault L, Bandak FA. Mechanisms of impact head injury. Int J Impact 1994;15(4):535–560 Adams JH, Graham DI, Gennarelli TA. Acceleration induced head injury in the monkey. II. Neuropathology. Acta Neuropathol Suppl 1981;7:26–28 Adams JH, Graham DI, Gennarelli TA. Head injury in man and experimental animals: neuropathology. Acta Neurochir Suppl (Wien) 1983;32:15–30 Gennarelli TA, Abel JM, Adams H, et al. Differential tolerance of frontal and temporal lobes to contusion induced by angular acceleration. In: Proceedings of the 23rd Stapp Car Crash Conference. SAE paper 791022.Warrendale, PA; Society of Automotive Engineers; 1979 Zhang L, Yang KH, Dwarampudi R, et al. Recent advances in brain injury research: a new human head model development and validation. Stapp Car Crash J 2001;45:369–394 Gurdjian ES. Head injury from antiquity to the present with special reference to penetrating head wounds. Springfield, IL: Charles C. Thomas Publishing; 1973 Zhou C, Khalil TB, King AI. A new model for comparing responses of the homogeneous and inhomogeneous human brain. In: Proceedings of the 39th Stapp Car Crash Conference. Warrendale, PA; Society of Automotive Engineers; 1995:121–136 Gorske T. Traumatic brain injury basics and beyond. Paper presented at: Pennsylvania Psychological Association Annual Convention; June 18–21, 2014; Harrisburg, PA Raymond DE, Crawford GS, Van Ee C, Bir CA. Biomechanics of temporo-parietal skull fracture from blunt ballistic impact. Paper presented at: The ASME Summer Bioengineering Conference; June 25–29, 2008; Marco Island, FL Needham CE. Blast Waves (Shock Wave and High Pressure Phenomena). Heidelberg, Germany: Springer; 2010 U.S. National Academies of Science Committee on Gulf War and Health: Brain Injury in Veterans and Long Term Health Outcomes. Military personnel with traumatic brain injury at risk for serious longterm health problems; more studies needed on health effects of blast injuries. December, 4 2008. Available at: http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID¼12436. Accessed May 15, 2010
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and is followed by a jetting of cold air, a test specimen placed at this location is exposed to a significant dynamic pressure resulting in large head accelerations.61 An overpressure measurement outside the shock tube, translated to dynamic pressure using Rankine-Hugoniot relations, will lead to incorrect values of overpressure—the calculated dynamic pressure could be significantly lower than actual overpressure downstream of the shock tube. Test data collected this way are often published as demonstrating the effects of blast overpressure on the brain, when the dominant effect was actually head acceleration due to dynamic pressure. The impact of this error can be significant. In blast tube experiments where a specific effort was made to prevent the accelerative motion of the head, the acceleration of porcine heads placed just outside the tube opening was, never the less, measured in excess of 1200 g and neurotrauma was observed.41 In contrast, ongoing tests led by one of the authors on porcine subjects placed fully inside the shock tube resulted in negligible head accelerations. Even with more than double the peak overpressure, the tests yielded little evidence of neurologic trauma using advanced imaging methods and postmortem histology. Another issue with blast-induced TBI research is determining a correct method to scale the results from animal models to humans. For pulmonary injuries, body mass has been used for decades to scale data from smaller and larger animals and to a human.62 For brain injuries, it is not yet clear whether this body mass scaling is appropriate, or whether blast overpressures and impulses should be scaled by head mass, brain mass, skull thickness, or other physical properties.61,63 In fact, proper scaling requires an understanding of the underlying mechanism of injury. In the absence of a clear understanding of the injury mechanism, we cannot determine the appropriate scaling methods, and in the absence of appropriate scaling methods, we cannot confidently estimate human injury thresholds using the data collected with animal models.
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22 Cernak I, Savic J, Malicevic Z, et al. Involvement of the central
42 Zhu F, Skelton P, Chou CC, Mao H, Yang KH, King AI. Biomechanical
nervous system in the general response to pulmonary blast injury. J Trauma 1996;40(3, Suppl): S100–S104 Lemonick D. Bombings and blast injuries: a primer for physicians. Am J Chin Med 2011;8(3):134–140 Courtney AC, Courtney MW. A thoracic mechanism of mild traumatic brain injury due to blast pressure waves. Med Hypotheses 2009;72(1):76–83 Chen Y, Huang W. Non-impact, blast-induced mild TBI and PTSD: concepts and caveats. Brain Inj 2011;25(7-8):641–650 Chafi MS, Karami G, Ziejewski M. Biomechanical assessment of brain dynamic responses due to blast pressure waves. Ann Biomed Eng 2010;38(2):490–504 Moss WC, King MJ, Blackman EG. Skull flexure from blast waves: a mechanism for brain injury with implications for helmet design. Phys Rev Lett 2009;103(10):108702 Goeller J, Wardlaw A, Treichler D, Weiss G. Cavitation as a possible damage mechanism for traumatic brain injury (TBI) from an improvised explosive device (IED) blast. DARPA SBIR Final Report. Arlington, VA: Defense Advanced Research Projects Agency (DARPA); 2013 Taylor PA, Ford CC. Simulation of blast-induced early-time intracranial wave physics leading to traumatic brain injury. J Biomech Eng 2009;131(6):061007 Taylor PA, Ludwigsen JS, Ford CC. Investigation of blast-induced traumatic brain injury. Brain Inj 2014;28(7):879–895 Zhang L, Yang KH, King AI. A proposed injury threshold for mild traumatic brain injury. J Biomech Eng 2004;126(2): 226–236 Nyein M, Jerusalem A, Radovitzky R, Moore D, Noels L. Modeling blast related brain injury. Paper presented at: The 26th Army Science Conference; December 1–4, 2008; Orlando, FL. Available at: http://handle.dtic.mil/100.2/ADA504193. Accessed June 12, 2010 Elder GA, Mitsis EM, Ahlers ST, Cristian A. Blast-induced mild traumatic brain injury. Psychiatr Clin North Am 2010;33(4): 757–781 Department of Energy. Manual for the Prediction of Blast and Fragment Loadings on Structures. DOE/TIC-11268. Amarillo, TX: Department of Energy, Amarillo Energy Office; 1980 Przekwas A, Tan X, Rule G, Iyer K, Ott K, Merkle A. Modeling articulated human body dynamics under a representative blast loading. Paper presented at: The ASME 2011 International Mechanical Engineering Congress & Exposition; November 11–17, 2011; Denver, CO Dagro A, McKee P, Kraft R, Zhang T, Satapathy S. A preliminary investigation of traumatically induced axonal injury in a threedimensional (3-D) finite element model (FEM) of the human head during blast-loading. 2013. ARL-TR-6504 website. Available at: http://oai.dtic.mil/oai/oai? verb¼getRecord&metadataPrefix¼html&identifier¼ADA588181. Accessed January 3, 2015 Panzer MB, Bass CR. Human results from animal models: scaling laws for blast neurotrauma. Paper presented at: National Neurotrauma Society Annual Meeting; July 22–25, 2012; Phoenix, AZ Yu AW, Wang H, Matthews KA, Bass CR. Mouse lethality risk and intracranial pressure during exposure to blast. Paper presented at: The Biomedical Engineering Society Annual Meeting; October 24– 27, 2012; Atlanta, GA Rafaels K, Bass CR, Salzar RS, et al. Survival risk assessment for primary blast exposures to the head. J Neurotrauma 2011;28(11): 2319–2328 Rafaels KA, Bass CR, Panzer MB, et al. Brain injury risk from primary blast. J Trauma Acute Care Surg 2012;73(4):895–901 Shridharani JK, Wood GW, Panzer MB, et al. Porcine head response to blast. Front Neurol 2012;3:70
responses of a pig head under blast loading: a computational simulation. Int J Numer Methods Biomed Eng 2013;29(3): 392–407 Versace J. A review of the severity index. In: Proceedings of the 15th Stapp Car Crash Conference. SAE Paper 710881. Warrendale, PA; Society of Automotive Engineers; 1971 Lissner HR, Lebow M, Evans FG. Experimental studies on the relation between acceleration and intracranial pressure changes in man. Surg Gynecol Obstet 1960;111:329–338 Prasad P, Mertz H. The position of the United States delegation to the ISO Working Group 6b on the use of HIC in the automotive environment. SAE Paper 821246. Warrendale, PA; Society of Automotive Engineers; 1982 Hutchinson J, Kaiser MJ, Lankarani HM. The head injury criterion (HIC) functional. Appl Math Comput 1998;96(1):1–16 Slobonik BA. SPH-4 helmet damage and head injury correlation. USAARL-80–7. Fort Rucker, AL: US Army Aeromedical Research Laboratory; 1980 McIntire BJ, Whitley P. Blunt impact performance characteristics of the advanced combat helmet and the paratrooper and infantry personnel armor system for ground troops helmet. USAARL Report No. 2005–12. Fort Rucker, AL: US Army Aeromedical Research Laboratory; 2005 Yoganandan N, Pintar FA, Kumaresan S, Maiman DJ, Hargarten SW. Dynamic analysis of penetrating trauma. J Trauma 1997;42(2): 266–272 Yoganandan N, Pintar FA, Zhang J, Gennarilli TA. Biomechanical aspects of blunt and penetrating head injuries. In: Gilchrist MD, ed. IUTAM Symposium on Impact Biomechanics: From Fundamental Insights to Applications. Heidelberg, GermanySpringer2005: 173–184 MacPherson D. Bullet Penetration: Modeling the Dynamics and Incapacitation Resulting from Wound Trauma. El Segundo, CA: Ballistic Publications; 2005 Committee on Review of Test Protocols Used by the DoD to Test Combat Helmets. Board on Army Science and Technology; Division on Engineering and Physical Sciences; National Research Council Review of Department of Defense Test Protocols for Combat Helmets. Test Protocols for Backface Deformation: Statistical Considerations and Assessment. Washington, DC: National Academies Press; 2014. Available at: http://www.nap.edu/openbook. php?record_id¼18621&page¼R1. Accessed January 3, 2015 Panzer MB, Wood GW, Bass CR. Scaling in neurotrauma: how do we apply animal experiments to people? Exp Neurol 2014; 261:120–126 Lockhart P, Cronin D, Williams K, Ouellet S. Investigation of head response to blast loading. J Trauma 2011;70(2):E29–E36 King AI, Yang KH, Zhang L, et al. Is head injury caused by linear or angular acceleration. Paper presented at: International Research Council on Biomechanics of Injury Conference; September 24–26, 2003; Lisbon, Portugal Duma SM, Manoogian SJ, Bussone WR, et al. Analysis of real-time head accelerations in collegiate football players. Clin J Sport Med 2005;15(1):3–8 Pellman EJ, Viano DC, Tucker AM, Casson IR; Committee on Mild Traumatic Brain Injury, National Football League. Concussion in professional football: location and direction of helmet impactsPart 2. Neurosurgery 2003;53(6):1328–1340, discussion 1340– 1341 Greenwald RM, Gwin JT, Chu JJ, Crisco JJ. Head impact severity measures for evaluating mild traumatic brain injury risk exposure. Neurosurgery 2008;62(4):789–798, discussion 798 Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA 2003;290(19): 2549–2555
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62 Bowen IG, Fletcher ER, Richmond DR. Estimate of man’s tolerance
characterization of a model of blast-induced mild traumatic brain injury. Contract No. W81XWH-11–2-0127. Tacoma, WA: Geneva Foundation; 2013 61 Needham CE, Ritzel D. Bad science yields wrong conclusion: blast testing issues and TBI. Front Neurology, in press
to the direct effects of air blast. Albuquerque, NM: Lovelace Foundation for Medical Education and Research; 1968 63 Wood G, Panzer M, Yu A, Rafaels K, Matthews K, Bass C. Scaling in blast neurotrauma. Paper presented at: International Research Council on Biomechanics of Injury Conference; September 11–13, 2013; Gothenburg, Sweden
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60 Long J. Combined effects of primary and tertiary blast on rat brain:
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Biophysical Mechanisms of Traumatic Brain Injuries Gregory T. Rule, MS2
Robert T. Bocchieri, PhD3
1 Physical Security and Applied Sciences Sector, Applied Research
Associates Inc., Dallas, Texas 2 Physical Security and Applied Sciences Sector, Applied Research Associates, Inc., San Antonio, Texas 3 Silicon Valley Office, Applied Research Associates, Inc., Los Altos, California
Jennie M. Burns, PhD2
Address for correspondence Lee Ann Young, BS, MA, Physical Security and Applied Sciences Sector, Applied Research Associates Inc, 13915 Preston Valley Pl, Dallas, TX 75240 (e-mail: [email protected]).
Semin Neurol 2015;35:5–11.
Abstract
Keywords
► ► ► ► ► ► ►
traumatic brain injury blunt trauma blast ballistic physics acceleration diffuse axonal injury
Despite years of effort to prevent traumatic brain injuries (TBIs), the occurrence of TBI in the United States alone has reached epidemic proportions. When an external force is applied to the head, it is converted into stresses that must be absorbed into the brain or redirected by a helmet or other protective equipment. Complex interactions of the head, neck, and jaw kinematics result in strains in the brain. Even relatively mild mechanical trauma to these tissues can initiate a neurochemical cascade that leads to TBI. Civilians and warfighters can experience head injuries in both combat and noncombat situations from a variety of threats, including ballistic and blunt impact, acceleration, and blast. It is critical to understand the physics created by these threats to develop meaningful improvements to clinical care, injury prevention, and mitigation. Here the authors review the current state of understanding of the complex loading conditions that lead to TBI and characterize how these loads are transmitted through soft tissue, the skull and into the brain, resulting in TBI. In addition, gaps in knowledge and injury thresholds are reviewed, as these must be addressed to better design strategies that reduce TBI incidence and severity.
The occurrence of traumatic brain injury (TBI) in the United States has reached epidemic proportions. The Center of Disease Control (CDC) reports that there are 2.2 million TBIs each year in the United States, including 50,000 fatalities and 280,000 hospitalizations. Traumatic brain injury accounts for 30% of injuries resulting in death in the United States.1 Within the military, TBI statistics vary widely due to the difficulties associated with diagnosing mild TBI2; however, reports indicate that up to 20% of returning veterans from Afghanistan and Iraq have head injuries.3 Although many individuals recover function in the months following TBI, others continue to experience chronic symptoms of cognitive, emotional, and physical impairment for months or years.4,5 Here we review the specific biophysical mechanisms of TBI associated with blunt, penetrating, and blast impact to the head. For each, we describe the physics of the interaction
Issue Theme Traumatic Brain Injury; Guest Editor, Geoffrey Ling, MD, PhD, FAAN, FANA
between the insult and the head, and discuss a summary of the state of the science with respect to injury thresholds.
Causes of Traumatic Brain Injury Traumatic brain injury is caused by a blunt, penetrating, or blast impact to the head. Key mechanisms by which energy may mechanically transfer into the skull and brain from external sources include direct impact by a solid object (blunt or penetrating impact) or fluid shock wave (blast impact), and rapid linear and/or rotational acceleration of the head, resulting in material stresses and strains. The direct impact of the head with a solid object may result in either a blunt or penetrating injury, with the type of injury dependent upon the mass, speed, and cross-sectional area of the object in comparison to the head.
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0035-1544242. ISSN 0271-8235.
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Lee Ann Young, BS, MA1
Biophysical Mechanisms of Traumatic Brain Injuries
Young et al.
Blunt Impact Blunt-impact head wounds are caused by objects that are usually of low velocity, high mass, and high cross-sectional area. Blunt impact to the head may cause lacerations and contusions on the scalp, localized deformation of the skull, coup/contrecoup impact (impact of the brain with the inner walls of the skull) caused by the rapid linear and/or rotational acceleration/deacceleration of the head, and increased intracranial pressure (ICP) gradients.6 The deformation of the skull transmits localized stress to the underlying tissues resulting in strains to the neural and neurovascular tissue. The rebound of the skull from deformation can cause a separation in the dura mater and skull, resulting in epidural hematomas.7 Contusions are often found at the coup and contrecoup sites of impact. Intracranial pressure gradients are generated by the inertia of the brain during head motion; when the brain lags behind the skull during linear acceleration, it “pushes” against the skull causing a pressure increase at the point of loading and a pressure decrease (negative pressure) distally to that point.7 Axons are stretched as a result of the shear stresses and strains caused by the gross motion of the brain inside the skull and these ICP gradients, leading to diffuse axonal injuries (DAIs) characterized by an enlargement of the axons at the locations where the microtubules are damaged.8 Rapid linear or rotational acceleration of the head may alone, without the impact of the head with a foreign object, cause coup/contrecoup injury. There are two theories regarding how rapid head acceleration results in brain injury. The first theory proposes that the brain is unable to rotate within the skull at the same velocity as the surrounding skull, leading to focal shear stresses and strains.6 Because the skull is most constraining in the frontal compartments and around the foramen magnum, this theory predicts a concentration of injuries near these locations, and in fact literature shows that there is a predominance of anterior fossa injuries regardless of whether the impact is frontal or occipital.9 The second theory proposes that diffuse shearing of brain tissues occurs at sites where adjacent tissues have sufficiently different densities to result in different rates of motion.10 Research into the diffuse injuries caused by rotation show that the damaging strains through inertial loading are greatest near the surface of the brain and decrease toward the center,11 such that low levels of rotational inertial loading affect only the cortex, and only the more severe loads result in damage down into the diencephalon.6 Animal models and numerical models have shown that DAI, acute subdural hematoma, and most other types of brain injury can be generated purely by rotational motion.12–15 However, more recently, the dominant consensus is that brain injuries result from a combination of translational motion, leading to direct site contusions and ICP, and rotational motion, leading to shear strains.16 Coup and contrecoup injuries appear to be pressure induced, and brainstem injuries appear to be associated with shear strain.17
Penetrating Impact Penetrating head wounds are caused by high-velocity objects, such as bullets or fragments, combined with low mass and Seminars in Neurology
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low cross-sectional area, or low-velocity knives and comparably higher mass and lower cross-sectional area. Penetrating objects of low velocity will cause lacerations on the scalp, fractures of the skull, and destruction or injury to the brain tissue in the immediate path of the penetrating object. For penetrating objects of sufficiently high velocity, there is an additional risk of increased ICP from a temporary cavity formed around the penetrating object. These high ICPs within the confines of the skull may cause the respiratory and cardiac centers of the medulla to fail, resulting in immediate death.16 For knife wounds or gunshot wounds, where most of the energy of the object is expended during penetration of the skull, there may only be localized damage and the patient may remain conscious. If the projectile or fragments of the skull remains inside the cranial cavity, these patients could be good candidates for débridement and survival is possible. If there is no penetration, but a fracture of the skull occurs, the patient may remain conscious, but could still be in danger of a subsequent increase in ICP from an epidural, subdural, and or subarachnoid hematoma.18,19
Blast Impact The environment in and around a blast is complex. For an exhaustive overview of blast physics, including shock and blast wave generation, Mach stem formation, and the physics of explosions, there are numerous sources that provide thorough descriptions.20,21 Individuals exposed to blast may be exposed to multiple, concurrent effects of blast such as thermal heating, ballistic impact from shrapnel and fragments, blunt impact, and acceleration from falling or striking walls and large displaced masses, and impact with fluid shock waves (blast overpressure) and acoustic waves, and in nuclear explosions, radiation. Exposure to blast overpressure alone can result in primary TBI caused by the direct impact of the shock against the head, direct transmission of blast wave energy through the head into the brain, and short duration accelerative motions of the head caused by temporal gradients in overpressure around the surface of the head. Like any potentially injurious loading environment, blast exposure establishes a transfer of energy from the external environment into the head. This transfer of energy ultimately results in tissue damage through several proposed underlying mechanisms, most of which have only limited validation in experimental data. These mechanisms include, but are not limited to, formation of air emboli or surges of fluid in the brain induced by thoracic pressure,22–24 shear and stress waves inducing micro (cellular and subcellular)25 and macro (gross morphological) level damage,26 physical deformation or flexing of the skull caused by pressure gradients,27 cerebrospinal fluid cavitation,28–30 and acceleration of the brain against the inside of the skull.31 To understand how blast waves may cause TBI, a fundamental understanding of how energy is deposited in the brain is required. The profile of the blast wave (e.g., number, magnitude, and duration of the blast overpressure peaks) is dependent on the characteristics of the explosive materials (e.g., dynamite [TNT] vs. improvised explosive device [IEDs]), the material in which the explosive is housed (e.g., metal
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7
contrecoup regions are shown to be more exposed to high magnitude pressures, and consequently greater injury, due to the reflection of the shock wave at the interface of the brain with the skull.42
Thresholds of TBI Blunt Impact and Acceleration The most commonly used criterion for ascertaining whether the head will sustain an injury caused by blunt impact or acceleration is the Head Injury Criterion (HIC).43 The HIC was proposed in 1970 based on the experimental results of 23 drop tests using five embalmed cadaver heads conducted in the late 1950s.44 The equation to calculate the HIC is shown in Equation 1:
where t1 is the initial time (s), t2 is the final time (s), and a(t) is the acceleration (g) at the center of gravity of the head. The acceleration window (t2–t1) is usually 15 milliseconds (ms) or 36 ms, depending upon the context of the impact (for automotive applications, it is usually 15 ms). This criterion is primarily used to design protective measures for automobiles. The Federal Motor Vehicle Safety Standard (FMVSS) 208 (occupant crash protection) and FMVSS-213 (child restraint systems) use a HIC of 1,000 as the threshold for head injury characterized by skull fracture or subdural hematomas. A head-injury risk curve was developed by Prasad and Mertz45 using postmortem human subjects to determine the relationship between the HIC and the probability of sustaining a lifethreatening injury. Based upon their data, a HIC of 1,400 gives a probability of sustaining a life-threatening brain injury of 0.5 and a HIC of 1,000 puts the probability at 0.18.46 The other injury criterion commonly used is the 150-g peak acceleration criterion. This criterion was based upon accident data from U.S. Army aviation accidents,47,48 and developed from experiments with the International Standards Organization (ISO) head form; like the HIC, following this criterion in the design of protective equipment can prevent skull fracture and subdural hematoma.
Fig. 1 Computational simulation of the exposure of a soldier to blast showing the profile of the peak overpressures across the surface of the entire body. (Wiri S, Needham C. Reconstruction of IED blast loading to personnel in the open. Paper presented at: 21st International Shock Interaction Symposium, International Shock Wave Institute; August 3–8, 2014; Riga, Latvia). Seminars in Neurology
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casing, air, or soil), the presence of reflecting objects near the exposed individual, the position and orientation of the individual to the blast, the stature and shape of the individual resulting in varying exposed cross-sectional areas of the body, and the use of protective equipment (e.g., Kevlar vests, helmets, etc.).32,33 Thus, each blast scenario can result in the exposure of an individual to a unique pressure wave profile and a unique deposition of energy into the brain resulting in a unique injury. As seen in ►Fig. 1, pressures across the head and body can vary widely. The pressure variations determine how energy affects the body in terms of implied forces, which can induce accelerations even without direct impact. In this scenario, the soldier experienced extremely high pressures on the shoulder and arm, which may have minimal physiological effect; however, exposures to the left ear exceeded 8 psi, which is sufficient to rupture the tympanic membrane.34 At higher pressure levels, from a larger blast or a smaller standoff distance, the pressure differentials across the head could cause both head deformation27 and acceleration.35 Ultimately, exposure to blast results in neuronal damage and tissue disruption, often detected in the traditional coup and contrecoup regions, and diffuse axonal injuries caused by induced stress and strains within the living tissues of the brain.36 Because these stresses and strains cannot be directly measured, measurement of ICP can provide a useful surrogate method for estimating energy deposition, particularly because ICPs have shown to correlate with fatality rates.37 In addition, computational modeling can provide significant insight into transmission and dissipation of blast energy through and into the brain tissue. Several computational models validated against both live and cadaver animal tests have shown that the skull generally behaves as a low-pass filter by which the higher frequencies are removed as the blast wave passes through the calvarium.38–41 Based upon these simulations, stress waves induce shear, spallation, implosion, and inertial effects within the brain tissue.33 Computational models have also shown that peak stresses and strains within the brain correlate with high-pressure regions at the coup and contrecoup locations30,36; the coup/
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Penetrating Impact
Discussion
Setting a single injury threshold for penetration injury is challenging due to the interrelationship between the velocity, mass, shape, and diameter of the projectile. The majority of the studies investigating trauma to all regions of the body use gelatin as the simulant for injury/wound quantification. 49 For studies investigating penetrating injury to the head, projectiles are fired into a rectangularshaped simulant without any backing material to approximate the skull, which is an inappropriate means to study the biomechanics of TBI. One study conducted by Yoganandan poured silicone dielectric gel (Sylgard 527; Dow Corning, Midland, MI) and ballistic gelatin into a sphere that approximated the skull. 50 The study used two different projectiles (9 mm and 25 caliber) to determine the formation and collapse of the temporary cavity inside the sphere and the pressures generated. Because the Sylgard gel has material properties closer to that of the human brain, Yoganandan claimed the gel was a more appropriate simulant for the study of penetrating brain injuries. Pressure distributions from experimental studies such as these can be used to validate future models for determining brain injury thresholds. Although no single injury threshold for the head exists, it is widely believed that any skull penetration from a high-velocity projectile is likely to cause instantaneous physiological incapacitation with a high likelihood of long-term disability or death.51 For this reason, all ballistic head protection is designed to a zeropenetration criterion, leaving behind-armor blunt trauma as the major risk of injury from ballistic threats because ballistic helmets are allowed to deform. The NIJ (National Institute of Justice) standard for ballistic helmets requires that backface deformation be no more than 16 mm for crown left and right impacts and no more than 25.4 mm for front and rear impacts, but there is no scientific basis to link these values to brain injury.52
Blast Impact There are no established injury criteria for blast-induced brain injury. Several efforts have been focused on developing criteria for brain injury using a variety of outcomes ranging from apnea37 to fatality.39 Recently, computational modeling, validated against available test data, has provided a first estimate for blast-induced brain injury criteria based on the occurrence of apnea immediately following blast exposure.53 In addition, the 150-g peak acceleration criterion and the HIC are the only criteria available to estimate the risk of head injury from accelerative motion. Unfortunately, these criteria only apply to gross accelerative motion in excess of 15 ms in duration; both modeling and testing has demonstrated that blast exposures of 30 to 40 psi peak overpressure can induce short duration, from < 1 to 6 to 7 ms, accelerations in excess of 400 g.54 Furthermore, criteria based on data from traditional blunt impact tests are likely not applicable to the blast impact as the mechanics involved are different, thus rendering conclusions based upon these criteria for blast-induced neurotrauma highly questionable. Seminars in Neurology
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Because experiments to investigate the threshold of TBI using live humans are unethical, research approaches to studying TBI have been limited to prospective or retrospective studies on people who are likely to develop TBI (e.g., athletes or veterans returning from war) or have been diagnosed with TBI (e.g., survivors of automobile collisions or terrorist attacks), or experimental testing on cadavers and animals. Accurate information regarding the biomechanical insult is difficult to obtain in most prospective studies and virtually all retrospective studies. The validity of cadaver tests is limited by the lack of muscle activation and physiological responses, and the validity of animal tests is limited by the anatomical and functional differences of the brain between species. Given these limitations, injury criteria and thresholds are based on indirect measures and global rigid-body kinematics. As a result, we have a limited understanding of the specific biomechanical processes that lead to TBI. The criteria used to define the threshold for injury caused by blunt impact to the head, the HIC and the 150g criteria, are sufficient for evaluating helmets in protection against skull fracture and hematoma; however, there are no criteria for the other types of brain injuries (e.g., cognitive dysfunction caused by neurochemical cascades) that can occur from blunt impact or rapid acceleration. Intense research into football-related impacts has attempted to correlate external accelerations with internal brain stresses using computer simulations,31,55–57 head surrogates, and real-time collection of acceleration data. Ongoing data collections with collegiate football teams 58 and upcoming joint Department of Defense and National Football League data collection efforts provide opportunities to collect massive amounts of data that have the potential to provide valuable insights into the threshold loads. However, both of these efforts are impeded by ambiguity in the definition and diagnosis of mild TBI, which makes it difficult to correlate measures of loads (pressures, forces, or impulses) in these databases to consistent levels of injury, particularly when the susceptibility of the brain to injury changes with repeated impacts.59 Additionally, these studies are challenged by the lack of subjects who are naïve to concussion, presenting a confounding factor of potential induced vulnerability.60 The primary challenge with respect to blast-induced TBI is the remaining uncertainty regarding injury mechanisms. Although many mechanisms have been proposed, inconsistencies in test methods, including exposure levels, approaches to blast generation and measures of effect, have resulted in confusing and sometimes conflicting results. One of the most significant experimental issues has been replication of blast environments in a laboratory setting. Shock tubes have proliferated in the last decade of blast neurotrauma research; however, many tubes are used incorrectly, placing the test specimen downstream of the shock tube exit (i.e., in front of the tube), rather than inside it. Because the shock wave rapidly expands outside the tube
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Conclusion Research to determine the dose–response curves or thresholds of TBI remain important in developing safer protective equipment and minimizing the risk of neurotrauma for both the civilian and military communities. For ballistic and penetrating impact neurotrauma, physiological-based behindhelmet blunt trauma criteria are needed. For blunt impact neurotrauma, criteria are needed for mild and moderate closed-head injuries, such as rapid linear or rotational acceleration, that do not involve skull fractures or subdural hematomas. For blast and to a lesser extent, blunt impact-caused neurotrauma, the greatest need continues to be clarity on the mechanisms of injury so that we can develop valid injury criteria in animal models and scale those criteria to humans. Investigation into the mechanisms of TBI will ultimately improve our ability to prevent, diagnose, and treat this debilitating disease.
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References 1 Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the
2
3
4 5 6 7
8
9 10
11 12
13
14
15
16
17
18
19
20 21
United States emergency department visits, hospitalizations, and deaths. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010 Levine B, Schweizer TA, O’Connor C, et al. Rehabilitation of executive functioning in patients with frontal lobe brain damage with goal management training. Front Hum Neurosci 2011;5:9 Theeler BJ, Flynn FG, Erickson JC. Headaches after concussion in US soldiers returning from Iraq or Afghanistan. Headache 2010;50(8): 1262–1272 Kraus JF, McArthur DL, Silberman TA. Epidemiology of mild brain injury. Semin Neurol 1994;14(1):1–7 Kraus JF, Nourjah P. The epidemiology of mild, uncomplicated brain injury. J Trauma 1988;28(12):1637–1643 Post A, Hoshizaki TB. Mechanisms of brain impact injuries and their prediction: a review. J Trauma 2012;14(4):327–349 Gurdjian ES. Re-evaluation of the biomechanics of blunt impact injury of the head. Surg Gynecol Obstet 1975;140(6): 845–850 King AI. Fundamentals of impact biomechanics: Part I—biomechanics of the head, neck, and thorax. Annu Rev Biomed Eng 2000; 2:55–81 Hardy WN, Khalil TB, King AI. Literature review of head injury biomechanics. Int J Impact 1994;15(4):561–586 Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations of blunt head injuries. Brain 1974;97(4):633–654 Ommaya AK, Thibault L, Bandak FA. Mechanisms of impact head injury. Int J Impact 1994;15(4):535–560 Adams JH, Graham DI, Gennarelli TA. Acceleration induced head injury in the monkey. II. Neuropathology. Acta Neuropathol Suppl 1981;7:26–28 Adams JH, Graham DI, Gennarelli TA. Head injury in man and experimental animals: neuropathology. Acta Neurochir Suppl (Wien) 1983;32:15–30 Gennarelli TA, Abel JM, Adams H, et al. Differential tolerance of frontal and temporal lobes to contusion induced by angular acceleration. In: Proceedings of the 23rd Stapp Car Crash Conference. SAE paper 791022.Warrendale, PA; Society of Automotive Engineers; 1979 Zhang L, Yang KH, Dwarampudi R, et al. Recent advances in brain injury research: a new human head model development and validation. Stapp Car Crash J 2001;45:369–394 Gurdjian ES. Head injury from antiquity to the present with special reference to penetrating head wounds. Springfield, IL: Charles C. Thomas Publishing; 1973 Zhou C, Khalil TB, King AI. A new model for comparing responses of the homogeneous and inhomogeneous human brain. In: Proceedings of the 39th Stapp Car Crash Conference. Warrendale, PA; Society of Automotive Engineers; 1995:121–136 Gorske T. Traumatic brain injury basics and beyond. Paper presented at: Pennsylvania Psychological Association Annual Convention; June 18–21, 2014; Harrisburg, PA Raymond DE, Crawford GS, Van Ee C, Bir CA. Biomechanics of temporo-parietal skull fracture from blunt ballistic impact. Paper presented at: The ASME Summer Bioengineering Conference; June 25–29, 2008; Marco Island, FL Needham CE. Blast Waves (Shock Wave and High Pressure Phenomena). Heidelberg, Germany: Springer; 2010 U.S. National Academies of Science Committee on Gulf War and Health: Brain Injury in Veterans and Long Term Health Outcomes. Military personnel with traumatic brain injury at risk for serious longterm health problems; more studies needed on health effects of blast injuries. December, 4 2008. Available at: http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID¼12436. Accessed May 15, 2010
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and is followed by a jetting of cold air, a test specimen placed at this location is exposed to a significant dynamic pressure resulting in large head accelerations.61 An overpressure measurement outside the shock tube, translated to dynamic pressure using Rankine-Hugoniot relations, will lead to incorrect values of overpressure—the calculated dynamic pressure could be significantly lower than actual overpressure downstream of the shock tube. Test data collected this way are often published as demonstrating the effects of blast overpressure on the brain, when the dominant effect was actually head acceleration due to dynamic pressure. The impact of this error can be significant. In blast tube experiments where a specific effort was made to prevent the accelerative motion of the head, the acceleration of porcine heads placed just outside the tube opening was, never the less, measured in excess of 1200 g and neurotrauma was observed.41 In contrast, ongoing tests led by one of the authors on porcine subjects placed fully inside the shock tube resulted in negligible head accelerations. Even with more than double the peak overpressure, the tests yielded little evidence of neurologic trauma using advanced imaging methods and postmortem histology. Another issue with blast-induced TBI research is determining a correct method to scale the results from animal models to humans. For pulmonary injuries, body mass has been used for decades to scale data from smaller and larger animals and to a human.62 For brain injuries, it is not yet clear whether this body mass scaling is appropriate, or whether blast overpressures and impulses should be scaled by head mass, brain mass, skull thickness, or other physical properties.61,63 In fact, proper scaling requires an understanding of the underlying mechanism of injury. In the absence of a clear understanding of the injury mechanism, we cannot determine the appropriate scaling methods, and in the absence of appropriate scaling methods, we cannot confidently estimate human injury thresholds using the data collected with animal models.
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22 Cernak I, Savic J, Malicevic Z, et al. Involvement of the central
42 Zhu F, Skelton P, Chou CC, Mao H, Yang KH, King AI. Biomechanical
nervous system in the general response to pulmonary blast injury. J Trauma 1996;40(3, Suppl): S100–S104 Lemonick D. Bombings and blast injuries: a primer for physicians. Am J Chin Med 2011;8(3):134–140 Courtney AC, Courtney MW. A thoracic mechanism of mild traumatic brain injury due to blast pressure waves. Med Hypotheses 2009;72(1):76–83 Chen Y, Huang W. Non-impact, blast-induced mild TBI and PTSD: concepts and caveats. Brain Inj 2011;25(7-8):641–650 Chafi MS, Karami G, Ziejewski M. Biomechanical assessment of brain dynamic responses due to blast pressure waves. Ann Biomed Eng 2010;38(2):490–504 Moss WC, King MJ, Blackman EG. Skull flexure from blast waves: a mechanism for brain injury with implications for helmet design. Phys Rev Lett 2009;103(10):108702 Goeller J, Wardlaw A, Treichler D, Weiss G. Cavitation as a possible damage mechanism for traumatic brain injury (TBI) from an improvised explosive device (IED) blast. DARPA SBIR Final Report. Arlington, VA: Defense Advanced Research Projects Agency (DARPA); 2013 Taylor PA, Ford CC. Simulation of blast-induced early-time intracranial wave physics leading to traumatic brain injury. J Biomech Eng 2009;131(6):061007 Taylor PA, Ludwigsen JS, Ford CC. Investigation of blast-induced traumatic brain injury. Brain Inj 2014;28(7):879–895 Zhang L, Yang KH, King AI. A proposed injury threshold for mild traumatic brain injury. J Biomech Eng 2004;126(2): 226–236 Nyein M, Jerusalem A, Radovitzky R, Moore D, Noels L. Modeling blast related brain injury. Paper presented at: The 26th Army Science Conference; December 1–4, 2008; Orlando, FL. Available at: http://handle.dtic.mil/100.2/ADA504193. Accessed June 12, 2010 Elder GA, Mitsis EM, Ahlers ST, Cristian A. Blast-induced mild traumatic brain injury. Psychiatr Clin North Am 2010;33(4): 757–781 Department of Energy. Manual for the Prediction of Blast and Fragment Loadings on Structures. DOE/TIC-11268. Amarillo, TX: Department of Energy, Amarillo Energy Office; 1980 Przekwas A, Tan X, Rule G, Iyer K, Ott K, Merkle A. Modeling articulated human body dynamics under a representative blast loading. Paper presented at: The ASME 2011 International Mechanical Engineering Congress & Exposition; November 11–17, 2011; Denver, CO Dagro A, McKee P, Kraft R, Zhang T, Satapathy S. A preliminary investigation of traumatically induced axonal injury in a threedimensional (3-D) finite element model (FEM) of the human head during blast-loading. 2013. ARL-TR-6504 website. Available at: http://oai.dtic.mil/oai/oai? verb¼getRecord&metadataPrefix¼html&identifier¼ADA588181. Accessed January 3, 2015 Panzer MB, Bass CR. Human results from animal models: scaling laws for blast neurotrauma. Paper presented at: National Neurotrauma Society Annual Meeting; July 22–25, 2012; Phoenix, AZ Yu AW, Wang H, Matthews KA, Bass CR. Mouse lethality risk and intracranial pressure during exposure to blast. Paper presented at: The Biomedical Engineering Society Annual Meeting; October 24– 27, 2012; Atlanta, GA Rafaels K, Bass CR, Salzar RS, et al. Survival risk assessment for primary blast exposures to the head. J Neurotrauma 2011;28(11): 2319–2328 Rafaels KA, Bass CR, Panzer MB, et al. Brain injury risk from primary blast. J Trauma Acute Care Surg 2012;73(4):895–901 Shridharani JK, Wood GW, Panzer MB, et al. Porcine head response to blast. Front Neurol 2012;3:70
responses of a pig head under blast loading: a computational simulation. Int J Numer Methods Biomed Eng 2013;29(3): 392–407 Versace J. A review of the severity index. In: Proceedings of the 15th Stapp Car Crash Conference. SAE Paper 710881. Warrendale, PA; Society of Automotive Engineers; 1971 Lissner HR, Lebow M, Evans FG. Experimental studies on the relation between acceleration and intracranial pressure changes in man. Surg Gynecol Obstet 1960;111:329–338 Prasad P, Mertz H. The position of the United States delegation to the ISO Working Group 6b on the use of HIC in the automotive environment. SAE Paper 821246. Warrendale, PA; Society of Automotive Engineers; 1982 Hutchinson J, Kaiser MJ, Lankarani HM. The head injury criterion (HIC) functional. Appl Math Comput 1998;96(1):1–16 Slobonik BA. SPH-4 helmet damage and head injury correlation. USAARL-80–7. Fort Rucker, AL: US Army Aeromedical Research Laboratory; 1980 McIntire BJ, Whitley P. Blunt impact performance characteristics of the advanced combat helmet and the paratrooper and infantry personnel armor system for ground troops helmet. USAARL Report No. 2005–12. Fort Rucker, AL: US Army Aeromedical Research Laboratory; 2005 Yoganandan N, Pintar FA, Kumaresan S, Maiman DJ, Hargarten SW. Dynamic analysis of penetrating trauma. J Trauma 1997;42(2): 266–272 Yoganandan N, Pintar FA, Zhang J, Gennarilli TA. Biomechanical aspects of blunt and penetrating head injuries. In: Gilchrist MD, ed. IUTAM Symposium on Impact Biomechanics: From Fundamental Insights to Applications. Heidelberg, GermanySpringer2005: 173–184 MacPherson D. Bullet Penetration: Modeling the Dynamics and Incapacitation Resulting from Wound Trauma. El Segundo, CA: Ballistic Publications; 2005 Committee on Review of Test Protocols Used by the DoD to Test Combat Helmets. Board on Army Science and Technology; Division on Engineering and Physical Sciences; National Research Council Review of Department of Defense Test Protocols for Combat Helmets. Test Protocols for Backface Deformation: Statistical Considerations and Assessment. Washington, DC: National Academies Press; 2014. Available at: http://www.nap.edu/openbook. php?record_id¼18621&page¼R1. Accessed January 3, 2015 Panzer MB, Wood GW, Bass CR. Scaling in neurotrauma: how do we apply animal experiments to people? Exp Neurol 2014; 261:120–126 Lockhart P, Cronin D, Williams K, Ouellet S. Investigation of head response to blast loading. J Trauma 2011;70(2):E29–E36 King AI, Yang KH, Zhang L, et al. Is head injury caused by linear or angular acceleration. Paper presented at: International Research Council on Biomechanics of Injury Conference; September 24–26, 2003; Lisbon, Portugal Duma SM, Manoogian SJ, Bussone WR, et al. Analysis of real-time head accelerations in collegiate football players. Clin J Sport Med 2005;15(1):3–8 Pellman EJ, Viano DC, Tucker AM, Casson IR; Committee on Mild Traumatic Brain Injury, National Football League. Concussion in professional football: location and direction of helmet impactsPart 2. Neurosurgery 2003;53(6):1328–1340, discussion 1340– 1341 Greenwald RM, Gwin JT, Chu JJ, Crisco JJ. Head impact severity measures for evaluating mild traumatic brain injury risk exposure. Neurosurgery 2008;62(4):789–798, discussion 798 Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA 2003;290(19): 2549–2555
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62 Bowen IG, Fletcher ER, Richmond DR. Estimate of man’s tolerance
characterization of a model of blast-induced mild traumatic brain injury. Contract No. W81XWH-11–2-0127. Tacoma, WA: Geneva Foundation; 2013 61 Needham CE, Ritzel D. Bad science yields wrong conclusion: blast testing issues and TBI. Front Neurology, in press
to the direct effects of air blast. Albuquerque, NM: Lovelace Foundation for Medical Education and Research; 1968 63 Wood G, Panzer M, Yu A, Rafaels K, Matthews K, Bass C. Scaling in blast neurotrauma. Paper presented at: International Research Council on Biomechanics of Injury Conference; September 11–13, 2013; Gothenburg, Sweden
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60 Long J. Combined effects of primary and tertiary blast on rat brain:
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