Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I J. Grafman and A.M. Salazar, Editors © 2015 Elsevier B.V. All rights reserved

Chapter 6

Injury biomechanics, neuropathology, and simplified physics of explosive blast and impact mild traumatic brain injury F.A. BANDAK1,3*, G. LING1, A. BANDAK3, AND N.C. DE LANEROLLE2 Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

1

2

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA 3

Integrated Services Group Inc., Potomac, MD, USA

INTRODUCTION Mild traumatic brain injury (mTBI) is a historically evolving term generally used to describe relatively less severe forms of brain injury without gross primary pathology in the brain such as subdural, subarachnoid, and intraventricular hemorrhages, etc. Recent attention to concussive brain injury occurring in sports and a special class of nonpenetrating brain injury following exposure to explosive blast has prompted additional research in the injury biomechanics and transient, as well as persistent, neuropathology of mTBI. A better understanding of the causal biomechanics of mTBI and related spatiotemporal neuropathology is needed to aid in the prevention and treatment of the condition. It is generally understood biomechanically that simple body movements such as vigorous twisting or jumping can cause the brain to experience some motion within the neurocranial cavity. More severe, intentional, body movements and contact exerting external loads on the head such as those occurring in sports activities can occur. Examples include gloved punches to the head in boxing, helmeted head collisions in American football, or unhelmeted in football (soccer). At high enough magnitudes, these head loadings can induce significant and potentially primary and/or irreversible secondary neuronal, axonal, and vascular disruption. In a less understood way, explosive blasts can induce complex shock loading states on the head that may produce similar organic disruptions as well as neurologic sequelae. Characterization of such head loading states and the effects of their

consequent “wounding mechanisms” on the brain and its function is a subject of active research. The objective of this chapter is to give a brief simplified description of underlying physics, injury biomechanics, and outcome neuropathology associated with mTBI as related in component fashion to conventional blunt impact and explosive blast shock waves.

HUMAN MECHANO-ANATOMY OF HEAD INJURY An appreciation of the macroscopic and microscopic morphology of the head–brain complex is essential in the biomechanical and neuropathologic assessment of injury mechanisms. Quantitative information on shapes, dimensions and constituent makeup of the components of the head–brain complex significantly affecting the injury process is essential in the biomechanics of explosive blast as well as impact mTBI. Here we give a description, moving from the outside inward, of what an external direct load will encounter as it contacts the head, beginning with the scalp. The scalp is the first line of defense against a load contacting the head and thus its shape and makeup play a very important role in the absorption and distribution of the imparted energy. It is a multilayered structure of about 1–1.5 cm thickness directly over the skull, made up of connected layers of skin, connective tissue, and the pericranium, which is a tough vascular layer covering the cranial bones making up part of the skull. The scalp provides both compression and shear relief by partially absorbing and redistributing

*Correspondence to: Dr. Faris A. Bandak, Professor, Department of Neurology, A1036, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Tel: +1-301-2997357, E-mail: [email protected]

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loads before they reach the skull. The skull and its mechanically complicated set of bones and sutures make up the neurocranial and the facial regions, both of which play a vital role in protecting the brain. The facial region often acts as an energy absorber situated farther outside while the neurocranial region encapsulates the brain and provides additional protection by distributing and absorbing energy passing through the scalp. The neurocranial bone plates consist of three layers referred to as the outer table, diploe, and inner table. The diploe consists of trabecular bone and is located between the other two layers, which are made up of compact bone. Next along the load entry path to the brain is the dura mater whose folding extensions, called the falx cerebri and falx cerebelli, line the inside of the skull and separate the cerebrum and the cerebellum respectively. Another fold of the dura mater is the tentorium cerebella, which separate the cerebrum from the cerebellum below. The primary load-bearing intracranial structures include the brain, cerebrospinal fluid, vascular structures, and the membranous coverings and partition structures. The cerebrum occupies most of the cranium and is composed of right and left hemispheres. The next layer below the dura mater is the arachnoid, a delicate membrane having a spider web arrangement of delicate collagen fibers that surround and envelope the outer surface of the brain. It is bounded from above by the dura and below by the pia mater, a thin transparent connective tissue layer that adheres to the surface of the brain. The pia consists of interlacing bundles of collagen fibers and some fine elastic fibers, in addition to many blood vessels. It also continues as a sheath around the many small vessels that penetrate into the brain. The region between the arachnoid and the pia mater is called the subarachnoid space. It contains cerebrospinal fluid and is traversed by the arteries of the brain and cranial nerves. The brain has four fluid-filled cavities or ventricles. Fluidic pressures in these cavities are potential contributors to regional brain damage from impact or blast. The brain’s complex vascular network is an integral part of its mechanical structure. Direct contact impact to the head can cause penetrating head injury, or nonpenetrating head injury also referred to as closed head injury (CHI). CHI can be defined as injury where the skull and dural membrane remain intact. A particular class of CHI consists of any type of traumatic damage affecting brain function and resulting from nonpenetrating mechanical head loading and can be diffuse or focal depending on the deposition and distribution of loading energy into the head. Diffuse brain injury involves damage to the various microstructures of the brain and is usually a consequence of relatively low energy, distributed head loading conditions, affecting a relatively substantial volume of the brain. Focal brain injuries on the other hand are the

result of concentrated damaging energy from direct loading on the head. This can occur as a result of direct impact loading on a relatively localized area or from geometric and material localization of a shock wave impinging on the head. Local impacts can cause tissue damage to the scalp and fracture of the skull in addition to brain injury, whereas explosive blasts can affect the brain in the absence of other cranial damage. The response of intracranial CSF is an important factor in the determination of loading effects on the brain. The mechanical impact response of the human head, and the consequent damage in the brain, are both affected by the presence of the CSF. The subarachnoidal CSF influences load transmission, mitigation, and shear concentration during dynamic interactions occurring between the brain and the inner surface of the cranial cavity (Bandak et al., 1999). Similarly, the ventricular CSF influences shear concentration in the inner regions of the brain but may have some important volumetric and boundary interface effects on the brain under exposure to explosive shock pressures. The CSF generally has a substantial effect on the pressure gradients occurring in the loaded brain as well as the relative movement between the brain and the dura mater. Impacts resulting in head injury can cause local accelerations and deformations, as well as whole-head translational and angular accelerations. Additionally, rotational head accelerations in some impact scenarios can reach large enough magnitudes to induce stretching in fiber tract regions (Bandak, 1996; Povlishock and Chirstman, 1996), whereas rotational accelerations are not thought to be significant in explosive blast CHI (de Lanerolle et al., 2011).

HEAD IMPACT AND ACCELERATION Head injury criteria have customarily relied on acceleration measures using relatively rigid dummy head forms. Some simplified definitions will be presented below to aid in the understanding of some of the general terminology used in these relationships.

Velocity and acceleration: translational and angular Velocity is the rate of change of position per unit time. It is a vector quantity, which means it possesses magnitude (speed) and direction. Translational velocity, commonly measured in ft/sec (m/sec), is the rate of change of linear position, while rotational velocity is the rate of change of angular position, also known as angular velocity and commonly denoted by o, with units of rad/sec. Acceleration is also a vector representation of the change in the magnitude and/or direction of velocity per unit time. Translational acceleration is commonly measured in (ft/sec)/sec, or ft/sec2 (m/sec2), or in units of G, the

INJURY BIOMECHANICS, NEUROPATHOLOGY, AND BLAST PHYSICS OF mTBI acceleration of the Earth’s gravity (approximately 32.2 ft/s2 or 9.8 m/s2). So an acceleration of “10 Gs”, for example, is equal to approximately 322 ft/s2, therefore a mass in an acceleration field of 10 G would weigh ten times more than in the 1 G field on Earth. In threedimensional linear motion, acceleration is expressed as a vector sum of three components, *

x + jay j^ y + jaz j^ z a ¼ jax j^

Where jaxj, jayj, jazj, and x^, y^, z^, denote the magnitudes and directions, respectively, and its measurement requires multiple direction accelerometers. Acceleration from rotational motion, however, is more involved. To understand simple rotational motion of the head, consider the simplified two-dimensional example (Fig. 6.1) given by Bandak (2005) of a head-like mass m having a center of gravity (CG) at point B and connected by a rod to a remote point A at a distance, r, from point B. If point B starts to move in a straight line in the horizontal direction, a force from the rod will act on it to cause it

an

at B

Trajectory

q r

A

Fig. 6.1. Rotational accelerations of a head-like mass connected by a rod and rotating around a point A. (Adapted from Bandak, 2005.)

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to move inwards in the radial direction resulting in the composite, familiar motion along a circular arc ultimately setting mass m in rotation about point A. The acceleration of mass m can be evaluated at any point along the arc and has two main components: a tangential component, at, which is the instantaneous translational acceleration along the arc, and a normal, an, which is radial, acting perpendicular to the arc as shown in Figure 6.1. The figure shows that the mass is tending to escape the circular arc and go free, but is constrained by the rod to move along the arc. Head acceleration measurements using crash dummies have traditionally been used in head injury assessment in transportation safety. Resultant acceleration at the CG of the dummy head has been relied upon in injury correlates. This quantity, however, does not provide the complete description of head dynamics, especially in situations involving complex translations and rotations. For example, motor vehicle crashes can subject the head to combined translational and rotational accelerations requiring more instrumentation to measure. A sensor with a nine-accelerometer configuration has been employed to measure both translational and rotational accelerations of the head in such cases. This sensor consists of three accelerometers at the head CG aligned along each principal body axis to measure resultant acceleration of the CG, and two a distance away from the CG on each principal arm to measure rotations about the CG in each direction. DiMasi et al. (1995) developed a technique to transform nine accelerometer data into an inertial reference frame suitable for loading computational models of the head. Figure 6.2 shows the head model under crash test conditions based on measurements made with a nine accelerometer sensor shown compared with the actual motion from crash test video. The figure illustrates the detail of motion captured by the nine accelerometer measurements, including the full translational and rotational motion during the crash, as well as the rotation during impact. Bandak et al. (2001) developed a process by which crash test data

Fig. 6.2. Crash test dummy measurements made with the nine accelerometer sensor imposed on the finite element model. The full motion of the head is captured as indicated by the nearly identical orientations of the model and the dummy head (Bandak et al. (2001)).

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F.A. BANDAK ET AL. Brain injury data (experimental models; clinical experience

Computational models (animal)

Computational models (human)

Material response data (animal)

Material response data (animal)

Brain injury measures (CSDM,DDM, RMDM)

A

Measurement of head loading (i.e. during a crash test)

Apply measured loads to human FE model

Evaluate against injury criteria

Neurotrauma?

B

Fig. 6.3. (A) Schematic of the SIMon concept. (Adapted from Bandak et al., 2001.) (B) Typical SIMon reconstruction of the head response during a crash test.

Fig. 6.4. Crash test head rotational accelerations from Figure 6.3 captured by SIMon and applied to head model showing the evolution of brain damage evaluated using the Cumulative Strain Damage Measure (CSDM).

can be combined with computationally based injury criteria (Bandak, 1996, 1997) to be used in head injury assessment, and automated this process into a PC ready tool called Simulated Injury Monitor (SIMon) (Fig. 6.3). SIMon is used to assess injury by directly imposing measured crash dummy accelerations on a computational model of the head (Bandak et al., 2001), and utilizing computationally based head injury measures developed by Bandak (1996, 1997). He called these measures, the cumulative strain damage measure, or CSDM (Fig. 6.4), the dilatational damage measure, or DDM, and the relative motion damage measure, or RMDM, and related each to a particular wounding process associated with a particular class of brain injuries.

Static and dynamic loading: contact or noncontact The impact or pure acceleration conditions discussed above impose dynamic, as opposed to static, forces on the head. Static loadings are usually the result of a gradual load application, and are generally considered to be independent of the time of application while dynamic loadings, on the other hand, are time-dependent and generally occur over a very short time period, referred to as the duration. Such forces can result from direct head impact, or head acceleration from forces reaching the

head through the neck and, thus, are categorized as either contact or noncontact. Figure 6.5 shows the mechanical features leading to a particular head injury or set of injuries, distinguishing primary injury (directly attributed to the cause) and secondary injury (developing as a result of the pathophysiologic consequences of the insult). Contact loadings involve direct impact to the head and produce a local indentation of the skull, resulting in local brain deformations and pressures. In addition, impact loading can involve abrupt stopping deceleration of the head, producing forces that are communicated to the brain through a localized path, starting first with the area of contact on the scalp and on to the brain through the skull and cerebrospinal fluid (CSF). This results in localized head deformations, as well as whole-head accelerations involving gross intracranial brain movement. Forces on the head through noncontact loading, on the other hand, pass through the neck and have an inherent rotational component (Bandak, 2005).

Classical acceleration head injury criteria Early head impact studies examined the relationship between direct head impact and the onset of linear skull fracture where concussion incidence was inferred from skull fracture results. Gurdjian et al. (1955) conducted

Biomechanics Categorization of CHI

HEAD LOADING

DYNAMIC

STATIC

Contact Head Loading

Non-Contact Head Loading

Restricted Relative Whole-Head Motion

Free Relative Whole Head Motion

Free Relative Whole Head Motion

Free Relative Whole-Head Motion

Low Whole-Head Acceleration

High Whole-Head Acceleration

High Whole-Head Acceleration

Low Whole-Head Acceleration

Small Impact Contact Area

Large Impact Contact Area

Long Duration Pulse

Intense Very Shory Duration Pulse

Localized Head Deformation

Predominat Head Motion is Angular

Predominant Head Motion is Angular

Limited Whole Head Motion

Local Brain Motion Primary Head Injury

Focal Extracranial soft Tissue Injury Skull Fracture Extradural Hemorrhage Coup Contusions Coup Hemorrhages Contre-Coup Contusions Contre-Coup Hemorrhage Intracerebral Hemorrhage Subdural Hemorrhage Parynchymal Laceration Microvascular Injury

Limited Gradient Brain Motion

Cross Brain Motion

Secondary Head Injury

Focal

Cerebral Edema Localized Brain Swelling Diffuse

Primary Head Injury

Focal

Subdural Hemorrhage Localized Intracranial Hemorrhages Brain Stem Injury Localized Hypoxia-ischerria

Secondary Head Injury

Focal

Localized Hypoxia-ischerria Localized Brain Swelling

Diffuse

Diffuse Brain Swelling Increased ICP Hypoxiz-ischerria

Axonal Injury

Brain Swelling Increased ICP Hyproxia-ischemia

Primary Head Injury

Secondary Head Injury

Focal

Diffuse

Focal Cerebral Edema Vasospasms Parynchymal Hemorrhages Ventricular Surface Hemorrphage Cerebral Contusions Air Emboli/ Cavitation

Axonal Injury Hyproxia-ischemia Microvascular Injury

Diffuse Petechial Hemorrhages BBB Breach

Axonal Injury Concussion / Mid Reversible? Prolonged LOC / Moderate Traumatic Coma / Severe Microvascular Injury

Edema

Concussion/ Mild , Reversible? Prolonged LOC/ Moderate

Brain Swelling Increased ICP

Microvascular Injury

Petechial Hemorrhages BBB Breach

Long Term Injury Physiological / Neurological

Headache Dizziness Memory Executive Function Anxiety CSF Abnormalities Auditory and visual sensitivities

Fig. 6.5. Biomechanical classification of head injury including contact impact and head acceleration and noncontact explosive blast shock wave loading. (Modified from Bandak, 2005.)

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direct contact head impact experiments on anesthetized primates monitoring mechanical and physiologic parameters in an attempt to correlate with concussion, coup and countercoup contusion, and relative brain motion, etc. Early work in this area contributed to the development of the Wayne State Tolerance Curve (WSTC), which expresses a relationship between acceleration level and impulse duration as a series of data points corresponding to decreasing acceleration tolerance for longer durations (Lissner et al., 1960). These data points were obtained based on cadaver studies. The WSTC became the basis for many current acceleration-based indices of head injury tolerance even though the original WSTC data only accounted for impacts lasting no more than 6 ms and addressed the incidence of linear skull fractures exclusively in unembalmed cadaver heads. One of the early derivatives of WSTC was a weighted impulse criterion developed by Gadd (1966), in which he used a logarithmic scale to linearly fit injury data and obtained a 2.5 power-weighting factor in what came to be known as the Gadd Severity Index (GSI). ð GSI  a2:5 dt < 1000 While the WSTC was developed based on impact profiles approximated as square pulses with an estimated effective acceleration, the GSI used the unaltered acceleration pulses, allowing Gadd to show that irregular acceleration pulses are more likely to produce more severe injuries. He also suggested that multiple peaks could be analyzed for injury potential by integrating the acceleration over the entire impulse profile, using his derived powerweighting factor. Gadd’s approach was further modified by Versace (1971) to obtain one of the early versions of what is now known as the Head Injury Criterion (HIC) based on resultant translational acceleration. It became a replacement for the GSI in the following form: ( ) 2:5 ð t2 1 aðtÞdt ðt2  t1 Þ HIC  Max ðt1 , t2 Þ t2  t1 t1 where (t1, t2) are time points during the acceleration pulse, (t2  t1) is the impact duration, the acceleration, a(t) is measured in units of G, and the time, t, in seconds. A HIC value of 1000 or greater was considered injurious. The applicability of HIC to long duration impacts and its lack of accounting for rotational head accelerations, however, is still a research question.

commonly used in the literature will be presented in what follows. Firstly, a significant player in this phenomenon is pressure. It is defined as a force (common units are pounds or newtons (N)) acting on an area (common units are square inches or square meters) along a direction perpendicular to the surface of that area. Therefore, pressure commonly has units of pounds per square inch (psi), or pascals (Pa) in the SI system, where 1 Pa  1 Newton/m2. One psi is equivalent to about 6895 Pa. Pressure can propagate in waves and requires a medium to propagate through. Sound is a pressure wave, which can travel in a variety of media including air. The sound we hear consists of simple acoustic, or sonic, waves which are infinitesimal pressure changes that move at a wave velocity specific to air. In general, explosive blast pressure waves of various speeds and character emanate from an explosive source and usually propagate through the air and impinge on surrounding objects such as buildings, vehicles, and, obviously, people. They combine, reflect, and transmit through different media at different speeds. Our focus here is on the generation and propagation of explosive blast waves as they travel toward and load the human head, and consequently, the brain. A particular and important type of pressure wave resulting by some means of driving waves at speeds faster than the sonic speed in the host medium is called a shock wave. In air, it is a sudden nearly discontinuous, fast-travelling disturbance in the form of an extreme rise in local pressure over a very short time interval, typically of the order of a couple of microseconds. The properties of air, particularly the compressibility, will cause the front of the resulting pressure disturbance to steepen very rapidly (Fig. 6.6) as the wave speed reaches and eventually surpasses the speed of sound in air. Typical shock waves are generated through detonation of an energetic material like a conventional explosive. An explosive is a substance capable of storing large amounts of chemical energy in a small volume which can be liberated upon activation of the explosive. The rapid release of energy initiates a phase change producing a powerfully expanding pressurized gas. Typical explosive blasts produce a leading shock wave with nearly instantaneous rise time, a characteristic that is potentially a direct mechanism of injury in explosive Steepening wave front

Direction of wave travel

EXPLOSIVE BLAST To appreciate a simplified physical understanding of explosive blast shock waves, some terminology

Fig. 6.6. Steepening of a pressure wave front in shock wave formation. From Ling et al. (2009).

INJURY BIOMECHANICS, NEUROPATHOLOGY, AND BLAST PHYSICS OF mTBI Incident pressure Dynamic pressure

Time (ms)

Time (ms)

Fig. 6.7. Incident and dynamic pressure time histories for an ideal explosive blast wave with peak incident pressure of 10 psi (upper plot) and 100 psi (lower plot).

blast mTBI. The extent and intensity of this process depends on several factors, including the size and chemical make-up of the explosive. Time history of incident pressure resulting from an ideal shock wave in the free field is shown in Figure 6.7, along with the accompanying dynamic pressure quantities to be discussed in a later section. The pressure remains at zero, which corresponds to ambient static pressure, until the shock arrives. A nearly instantaneous peak pressure is felt when the shock arrives at the fixed measurement point some distance from the center of the explosion. The magnitude of the peak incident pressure value attained and the arrival time both depend on the type of explosive, explosive charge weight, and distance from the center of the explosion. A pressure history resulting from an ideal explosive blast in the free field with no ground reflection is well characterized by a modified Friedlander (Baker, 1973) equation of the form,   0 t  t0 a tt ta e PðtÞ ¼ P0 + Ps 1  ta Where P0 is ambient pressure, Ps is incident absolute pressure, t0 is the arrival time of the shock, ta is the positive duration of incident overpressure, and a is an exponential decay constant. A typical incident and dynamic pressure time history measured at a point a certain distance from a high explosive spherical charge is shown in Figure 6.7 for a 10 psi peak incident pressure (upper plot) and a 100 psi peak incident pressure (lower plot). The two magnitudes illustrate the different dynamic pressure effects occurring for the pressure range relevant to our discussion here and show differences for different pressures ranges reported in blast TBI experiments. Definitions and some relevant terminology will be

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discussed next to help better understand shock wave pressures and their effects on the brain.

Static, dynamic, incident, and reflected pressures and overpressure Static pressure is the force component per unit area at a point in a fluid medium acting normal to a surface moving with the fluid. It does not account for the pressure created when there is motion, or flow, of the fluid relative to the surface. Static pressure can be measured using a “point probe” with minimal effect on the flow in which it is placed. The pressure component concerned with fluid motion is called the dynamic pressure. In fluid flow, the total pressure is the sum of the static and dynamic pressures. The dynamic pressure for incompressible (i.e., fluid density remains constant), frictionless, flow given by 1 ðPd Þincomp ¼ rv2 2 Where r is the density and v is the velocity of the fluid. So, dynamic pressure is related to the kinetic energy of an ensemble of fluid particles, and is a characteristic of the inertia and movement associated with flow. The relevant case to shock waves is the compressible flow condition. For compressible flow of an ideal gas, the dynamic pressure is given by 1 ðPd Þcomp ¼ gPs M 2 2 Where g is a gas constant, Ps is the static pressure, and M is Mach number, defined as the ratio of the flow velocity and the speed of sound in the fluid. These effectively are expressions of the kinetic energy per unit volume of air behind the shock front. Note that dynamic pressure is an overpressure and not an absolute pressure, and that its value is zero if the flow is not in motion. The initial shock wave pressure peak that a typical gauge would measure is usually the incident overpressure, where “overpressure” refers to the difference between the absolute incident pressure and the ambient static pressure. So, the units of overpressure are sometimes given in psig, where the suffix “g” denotes “gauge” pressure, as opposed to psia, where “a” denotes absolute pressure. A valid measurement of overpressure can never be below the negative of absolute static ambient pressure, since that would imply a negative absolute pressure. The incident pressure can be estimated at the leading edge of an object subjected to a shock wave by using a “point probe”, practically, a side-on gauge that does not affect the flow, placed at a small distance upstream of the object. It can also be measured at a reasonable transverse distance (normal to the flow

F.A. BANDAK ET AL.

direction) from the leading edge of the object, by a gauge placed side-on in the free stream. When a shock wave contacts an object, the resulting pressure is called the reflected pressure. It results from the change in momentum as a shock wave is reflected from a surface obstructing the flow. Usually, reflected pressure refers to the pressure from simple conditions like a shock wave impinging on a rigid flat surface normal to the flow direction. More complicated reflection conditions occur when the surface has curvature or obliqueness and even more complicated conditions arise when the surface is not rigid but compliant and gives way under the load of the shock wave. These complicated conditions are ones which apply to the head, making the measurement and interpretation of explosive blast head loading a challenging task. Weak shocks with Mach numbers slightly greater than 1.0 result in peak reflected pressures twice the magnitude of the incident pressure. Very strong shocks, however, can induce a reflected pressure 10 times or more than the magnitude of the incident pressure.

The positive and negative phases Shortly after the arrival of the shock wave, the incident pressure reaches a peak and then decays exponentially back to zero over a time interval denoted as the positive duration. During the positive duration, the idealized shock flow undergoes compression where the gas density increases sharply. In general, the duration of the positive phase increases monotonically with distance from the explosive, for a given explosive type and charge weight. The exception is for very small distances from the explosive, where the duration increases sharply with a decrease in distance from the source. At sufficient distance from the explosion, the pressure will continue to decrease after the positive phase reaching a relatively lower magnitude negative pressure state, referred to as the negative phase, where the pressure eventually returns to zero. During this phase, reverse air flow results in pressure below ambient usually having a much longer duration than the positive phase. This can be sustained for several seconds in sharp contrast to the duration of the positive phase, which typically is a few milliseconds or possibly tens of milliseconds. During most of the negative phase the direction of the particle velocity is counter to the direction of the explosive blast wave, with a relatively weak wind being directed towards the center of the explosion. Near the end of the negative phase, the flow reverses again away from the explosive, but the magnitude of the flow velocity is reduced considerably. The extent of the negative phase is shown in Figure 6.8 for a constant charge weight at varying measuring distances from the free field explosion. Note that at closer distances the negative phase is virtually

5 lb TNT Blast 25 10 ft 15 ft 20 ft 25 ft

20 Incident Overpressure (psi)

96

15 10 5 0 –5 –5

15

5

25

35

Time (ms)

Fig. 6.8. Effect of distance from an explosive source on ideal free field pressure.

nonexistent, having a very low pressure. At a sufficiently close distance, the negative phase will not be present at all. At larger distances, such as 20 ft from the 5 lb TNT charge, there is a negative phase that can be significant in terms of both magnitude and duration, as illustrated in Figure 6.8.

Explosive blast impulse Blast impulse is usually defined as the integral of pressure P(t) over time, ð t2 I ¼ PðtÞdt t1

The units of explosive blast impulse in this form are usually psi-millisecond in the English system and Pa-sec in the SI system. An explosive blast-related impulse that is commonly reported is the impulse taken over the positive duration. For the case of a modified Friedlander given earlier, the incident overpressure can be integrated analytically to obtain an incident positive impulse given by I¼

Ps ta ½a + ea  1 a2

Where Ps is the peak incident overpressure, a is the exponential decay coefficient, and ta is the positive duration. When considering explosive blast impulse loading on animal subjects, humans, or structures in general, it is useful to consider the reflected pressure as a basis for loading, since that is the pressure to which the object is subjected (e.g., the pressure “felt” by the object).

Complex waves Complex shock waves, as opposed to simple free field shock waves, are characterized by complicated compressible flow patterns, which arise from reflections

INJURY BIOMECHANICS, NEUROPATHOLOGY, AND BLAST PHYSICS OF mTBI 97 off, and diffraction around, objects in the path of an propagates through the expansion chamber at supersonic explosive blast shock wave. They can develop from speed. During the same brief time interval (milliseconds explosions within or exterior to a structure as well as or possibly fractions of milliseconds), a rarefaction at points near the ground from ground reflection. In conwave, also referred to as a Prandtl-Meyer expansion trast with a free field Friedlander pressure time history, wave, starts to form at the position of the diaphragm which always has a single peak incident pressure at the and propagates in the opposite direction. These expanshock arrival time, a typical complex wave can have sevsion waves reflect at the closed end of the shock tube eral large peaks, with the largest one not necessarily adjoining the driver gas chamber, changing their direcarriving first. Pressure measurements typically last lontion to travel toward the expansion section. In contrast ger for complex waves than for those in the free field to a compressed gas driven shock tube, an explosive since pressure peaks can occur at relatively late times charge driven shock tube relies on the generation of a after detonation. In addition to multiple shock reflecshock wave through detonation of an explosive charge tions, focusing effects can result in wave reinforcement directly generating a shock wave. It is important to note, and peak pressure amplification. Focusing effects often though, that explosive blast characteristics can vary occur near corners inside structures, where a single among various modes of shock generation. spherical shock wave can reflect from each wall with Blast pressure dosimeters the resulting reflected waves meeting at a single location somewhat removed from the corner. Analytic solutions A blast pressure dosimeter is a small sensor device which of compressible flow problems are quite difficult and can detect and record pressures arising from a nearby are rarely possible for complex blast waves. Typically, explosive blast. In the evaluation of explosive blast loadcomputational methods using, for example, finite difing on the head, measurement of pressures at distinct ference or finite element techniques are used for deterpoints on the head is necessary. Warfighter worn explomination of the distribution of pressure, velocity, and sive blast dosimeters to estimate real world shock pressure exposure on the head are very useful and require temperature over time and space. consideration of several relevant points. Placement, mounting, and synchronization of the sensors can proShock tubes vide sufficient information, such as peak measured presShock tubes are relatively simple blast test devices gensures and shock arrival times for the various sensors, to erally utilized in a laboratory setting to generate shock make it possible to ascertain the direction of the initial waves with or without the use of an explosive charge. incoming explosive blast. This is necessary in order to They can be used to conduct simulated blast experiments be able to properly estimate the reflected pressure and acting on test objects placed in or outside the tube. Small thus the true pressure felt by the surface underlying as well as large shock tubes have been used to study blast the mounted dosimeter. Realistic scenarios where no sinbrain injury in small and large animal models. Generally, gle explosive blast sensor on a soldier’s head is directly a shock tube is a device which consists of a duct of ciraligned with the explosive blast direction can occur in the cular or rectangular cross-section, with a large length-tofield. These are manageable as long as the data is suffidiameter ratio (e.g., L/D > 20), divided into two separate cient to determine the direction of the explosive blast chambers usually by a narrow flanged section containing wave relative to the head. Additional measured data such a diaphragm. The diaphragm separates the gas in the as head acceleration can provide useful information driver chamber that is filled with gas at a high pressure, along with pressure measurements to help estimate from an expansion, or driven chamber, which is mainexplosive blast direction by providing direction of tained at a much lower pressure. Commonly, the gas motion of the head if a vertical axis of symmetry exists in the expansion chamber is kept at atmospheric presor at least is approximately symmetric about an axis sure. A shock tube can be either open or closed at the passing through its CG. This should be the case for the expansion chamber end of the tube. head and helmet. For helmet mounted sensors, it is essenInitiation of a shock wave generation sequence begins tial that the fit on the head and the characteristics and the with bursting the diaphragm either passively by increasreproducibility of the load transmission to the head is ing the driver gas pressure to a sufficient threshold for clearly understood so that the pressure measurements rupture, or actively, by means of a mechanical actuator can be interpreted into more accurate loads on the head. impacting and penetrating the diaphragm. Commercially In practice, the physical separation and degree of “tight available diaphragms are designed to rupture at specifit” of the helmet mounted on the head can lead to head fied pressure differentials, and many have scored fracaccelerations that differ from the helmet accelerations. ture lines at various depths in order to achieve this. The Supplementary measurements such as torso-mounted rupture of the diaphragm initiates a series of compresaccelerometers can also provide additional data for valsion waves, which merge rapidly into a shock wave that idation of blast direction on the head.

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F.A. BANDAK ET AL. 12 Iraq war veterans with one or more explosive blast NEUROPATHOLOGY OF EXPLOSIVE exposures and a diagnosis of mTBI and post-concussive BLAST mTBI syndrome compared to 12 cognitively normal commuHuman studies nity volunteers, report that the veterans with mTBI had a decreased cerebral metabolic rate of glucose HISTOPATHOLOGY utilization in infratentorial structures (cerebellar hemiVery few histopathologic data exist on explosive blast spheres, vermis and pons) and also in the medial tempoexposed humans who have presented with symptoms ral cortex. Two significant interpretative issues affect of mTBI. Goldstein et al. (2012) reported on postmortem this study. The first is that the control population is sigexamination of four males (22–45 years) with a history of nificantly older than the veteran population. The second exposure to explosive blast. Two were comorbid with limitation of the study is that 10 of the 12 veterans were post-traumatic stress disorder (PTSD) and had a prior hisalso comorbid for PTSD, making it difficult to detertory of concussion at an early age, while the other two had mine the cause of the observations. The study does not no PTSD and only one had a previous history of concusreport if the two non-PTSD subjects differed or not from sion. Their brains were compared to brains of subjects those with PTSD. Consistent with the thesis of this study, without a history of explosive blast exposure and athletes a case study of a soldier with primary explosive blast with history of impact. The scope of the study is mostly injury reports a cerebellar white matter lesion on MRI focused on the expression of phosphorylated and non(Warden and French, 2005). phosphorylated tau proteins. In the subjects with exploDiffusion tensor imaging (DTI) has also been applied sive blast exposure and/or impact, perivascular foci of to investigate the neuropathologic changes in the blasttau-immunoreactive neurofibrillary tangles (NFTs) and exposed human brain. MacDonald et al. (2011) used glial tangles in inferior frontal, dorsolateral frontal, pariDTI to compare uncomplicated mTBI in 63 military peretal and temporal cortex, particularly near sulcal depth, sonnel with primary explosive blast exposure plus were reported. Phosphorylated tau immunoreactive dysanother impact-related CHI, and 21 military personnel trophic axons and NFTs were also found in the superficial with explosive blast exposure and other injuries but no layers of the frontal and parietal cortex and the hippoclinical diagnosis of mTBI. Subjects with mTBI were campus. Tau immunoreactive degenerating axons, axon reported to have marked abnormalities in the middle cerretraction bulbs, and axon dystrophy were observed in ebellar peduncle, cingular bundles, uncinate fasciculus, subcortical white matter adjacent to cortical tau patholanterior limb of the internal capsule, middle cerebellar ogy and perivascular areas. Immunoreactive activated peduncles, and in the orbitofrontal white matter. Few clusters of microglia were also reported in subcortical abnormalities were noted in the corpus callosum and white matter underlying focal tau pathology but not in posterior limb of the internal capsule. In a subgroup unaffected brain regions. of 18 with mTBI a greater number of abnormalities were Earlier studies (Mott, 1917; Cramer et al., 1949; Hirsch reported. All subjects had negative conventional MRI. and Ommaya, 1972; Murthy et al., 1979) reported neuroThe findings were interpreted as evidence of traumatic pathologic features such as small hemorrhages in white axonal injury. This study does not determine if these matter, chromatologic changes in neurons indicative of changes were from explosive blast and/or concomitant neuronal injury, and subdural hemorrhage. Reviewing a head impact to which this cohort of subjects was also few cases where primary explosive blast was thought to exposed. It was further pointed out that while the abnorbe the cause of death, Mott (1917) described several malities observed may be consistent with DTI, they are microscopic features he attributes to explosive blast. not diagnostic and do not exclude other interpretations These include an “extremely congested cortex”, enlargesuch as evolving extracellular edema or mild gliosis ment of perivascular space, subpial hemorrhages, (Xydarkis et al., 2011). venous engorgement, hemorrhage in white matter into Davenport et al. (2012) also used DTI to compare a myelin sheath and perivascular spaces, and chromatolygroup of 25 military personnel with, and 33 without, sis (Taber et al., 2006). explosive blast mTBI. A history of civilian nonexplosive blast TBI was equally common across groups. Blast NEUROPATHOLOGIC CHANGES OBSERVED THROUGH mTBI is described as “associated with a diffuse, global BRAIN IMAGING STUDIES pattern of lower white matter integrity” which was not Though standard structural imaging studies of explosive affected by previous civilian mTBI (Davenport et al., blast-exposed persons have not yielded observations of 2012). Lower fractional anisotropy (FA) was observed any significant brain injury, more recent studies with in the genu and splenium of the corpus callosum, bilatnewer imaging techniques have begun to report exploeral anterior thalamic radiations, right corticospinal sive blast associated changes. A fluorodeoxyglucose tract, bilateral inferior frontal occipital fasciculus, bilatpositron emission tomography (FDG-PET) study on eral inferior longitudinal fasciculus, and left superior

INJURY BIOMECHANICS, NEUROPATHOLOGY, AND BLAST PHYSICS OF mTBI longitudinal fasciculus. Additional individuals with more than one explosive blast tended to have a larger number of voxels with lower FA than those with a single explosive blast. Davenport et al. (2012) concluded that the neurologic effects of explosive blast mTBI are diffuse, widespread, and spatially variable. The interpretation of this study as relating to the effect of pure explosive blast shock is difficult as the study defines blast-related injuries to include secondary and tertiary effects of being thrown against the ground or being hit by a projectile. Our recent studies of blast-exposed warfighters with mTBI, using high field strength (7 tesla) magnetic resonance spectroscopic imaging (MRSI) found significant injury to the anterior hippocampus, with greater injury to the right hippocampus and about a 20% reduction in volume compared to the left. The degree of injury is greater in those persons exposed to multiple blast than to a single blast (Hetherington et al., 2013, 2014) (Ch. 20). Such injury is independent of comorbidities such as PTSD or depression. These MRSI studies suggest that exposure to pure blast pressure waves can result in significant injury to the brain.

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scenario, and (3) a four-walled structure to simulate a building. The animals were protected so that only the head was exposed directly to the explosive blast and the head was constrained to limit head accelerations. All animals were examined 2 weeks post-explosive blast, which is a “short” duration compared to the post-explosive blast interval over which the effects of injury manifest in humans, namely months to years. A unique and quite interesting pattern discovered on histopathologic examination of the brains revealed a periventricular distribution of b-APP-positive injured axons in all three scenarios (Fig. 6.9). However, this was not the case in the major white matter tracts where axonal injury was not observed. Mild b-APP-positive axons were seen in the cerebellum of only two of the 40 explosive blast-exposed animals examined. A second distinctive feature discovered was the activation and proliferation of astrocytes, which were prominent in the hippocampus and frontal cortex (Fig. 6.10). This feature was statistically significant only for animals in the vehicle and four-walled structure. Activated microglia were also seen in the corpus callosum (Fig. 6.11). No injured neurons were seen in routine H&E stained sections, neither was there evidence of petechial hemorrhage.

LARGE ANIMAL STUDIES

SMALL ANIMAL STUDIES

Several animal model mTBI studies have attempted to investigate short- and long-term neuropathologic effects of pure explosive blast shock waves on the brain. De Lanerolle et al. (2011) used a large animal model (swine) to study pure explosive blast shockwaves on the brain under three operationally relevant situations: (1) an explosive blast shock tube to simulate the free field condition, (2) a vehicle structure to simulate a HUMVEE

Two small animal studies exposed rats to blast (Garman et al., 2009; Long et al., 2009) in a shock tube simulating free field blast. In the Long et al. study, the animal was placed outside the tube closely adjacent to its outlet, whereas in the Garman et al. study, the animal was placed within the tube. In both studies the animal was protected but for the head though by different methods. Both studies report axonal injury (as determined by silver

Fig. 6.9. Diffuse and distinctive axonal injury pattern. Left: Computer assisted plot of the periventricular location of b amyloid precursor protein (bAPP) immunoreactive axons in animals exposed to blast. Right: Photomicrograph of APP immunoreactive axons. From de Lanerolle et al. (2011).

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Fig. 6.10. An outline of a coronal section of the swine brain showing activation of astrocytes by blast through GFAP immunostaining in the hippocampal dentate gyrus and CA1 areas. Animals exposed to blast pressure show an increased activation of GFAP positive astrocytes in the hippocampus. (A) Control, (B) blast exposed. From de Lanerolle et al. (2011).

Fig. 6.11. Microglial activation (IBA1 immunoreactivity) in only deep white matter areas. (A) Control, (B) blast exposed. From de Lanerolle et al. (2011).

impregnation staining methods) as a most significant aspect of injury and in the extreme cases the study by Long et al. (2009) reported hemorrhage and extensive necrosis with damage being bilateral but more on the side ipsilateral to blast. Axonal damage was seen as areas of dark silver stain are also widespread. In the study by Garman et al. (2011), the exposed animals were neuropathologically examined at three post-explosive blast time points (24 h, 72 h, and 2 weeks). Neuronal and axonal injury was assessed with a cupric silver impregnation staining methods. “Scattered foci of neuron degeneration” were observed at all time points, with minimal to mild degrees of neuronal degeneration. There was no consistent pattern of neuronal degeneration within the brain, but the entorhinal cortex, frontal cortex,

CA1 pyramidal cell layer of hippocampus, cerebellar cortex, parietal, piriform, insular temporal and retrosplenial cortex were identified as locations. Though degenerating Purkinje cell bodies were rare, Purkinje neuron dendritic degeneration was common (Garman et al., 2011). The study did not confirm these observations with an alternative method such as FluroJade B staining for neuronal injury or TUNEL stain for apoptosis. Axonal injury was reported as prominent in the cerebellar deep white matter and brainstem regions. Several other pathways are also reported to show damage – optic nerve and tract, internal and external capsules, thalamic pathways, the cerebral and cerebellar peduncles, trigeminal tracts, trapezoid body and pyramids. Silver degeneration techniques for identifying injured axons have their strengths

INJURY BIOMECHANICS, NEUROPATHOLOGY, AND BLAST PHYSICS OF mTBI and weaknesses. Neither study provides adequate corroborative evidence on the basis of b-APP immunoreactivity of these fibers.

NEURPOPATHOLOGY OF NONBLAST IMPACT mTBI Human brain A whole-brain fMRI study of 30 subjects with mTBI (GCS 13–15) compared their resting state whole brain functional connectivity identified by independent component analysis of fMRI data with that in 30 controls (Stevens et al., 2012). Voxel wise group comparisons found abnormal mTBI functional connectivity in every brain network identified by independent component analysis, including visual processing, motor, limbic and many circuits thought to be involved with executive cognition. Abnormalities included not only functional deficits but also enhancements. Several networks showed only enhanced regional functional connectivity, but not deficits, in mTBI. These included a secondary visual processing network, the limbic circuit, and cingulo-opercular circuit associated with mental set maintenance and cognitive control. Functional connectivity was disrupted in mTBI without evidence for vascular-related damage to neurons themselves. While this study suggests changes in axonal pathways involved in these networks, whether such changes can be confirmed histologically remains unknown. Information on the neuropathologic changes in the human brain due to nonblast closed head mTBI is very scarce because the condition is rarely fatal. Available studies examine the brains of subjects with mTBI who died shortly afterwards due to other causes. Axonal damage is a common pathologic finding of such studies. Adams et al. (1980, 1982) examined the neuropathology of subjects with nonmissile closed head trauma, but none of their subjects can be classified as having mTBI on the basis of the GCS or periods of post-traumatic unconsciousness. A study was done (Adams et al., 1980) on 151 autopsies of patients with head injuries who survived 6 hours to 21 months. About equal numbers had injuries due to motor vehicle crashes and falls. In patients who survived many months after their injury there is a characteristic loss of white matter in the cerebral hemispheres with ventricular enlargement. In short-term survivors, microscopic examination showed axonal injury in corticospinal tracts and the medial lemniscus. In 19 subjects who did not regain consciousness from the moment of impact until death (12 hours to 21 months) there was diffuse damage to white matter. Adams et al. (1989) also examined the brains of 635 autopsies of fatal, nonmissile head injuries. Twenty-nine percent of these

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were identified as having DAI. On the basis of these studies they define three grades of DAI. Grade 1 includes axonal damage in cerebral hemispheres including the corpus callosum, in the brainstem and occasionally in the cerebellum. Grade 2 DAI includes in addition focal lesions in the corpus callosum. Grade 3 DAI has all the features of grade 2 with in addition focal lesions in the dorsolateral quadrant of the pons. Those with short survival (days) have large numbers of axonal bulbs throughout the white matter of the cerebral hemispheres, cerebellum and brainstem, with adjacent focal lesions. Those of intermediate survival time (weeks) included large numbers of small clusters of microglia throughout the same areas that had axonal injuries along with diffuse, nonspecific astrocytosis. Those with long survival times (vegetative for months) showed Wallerian degeneration in the same areas and the spinal cord with enlarged ventricles. Thus it appears that the degree of injury following trauma to the brain evolves over time. The study also points out some additional features of pathology. These observations suggest that DAI may be associated with the relative motion of the brain within the cranial cavity. More recent studies by Blumbergs et al. (1994) studied six patients aged 59–89 years who sustained head injury with a Glasgow Coma Scale score of 14–15 – the range for mTBI – and died 2–99 days later. These subjects showed axonal injury (identified by b-APP immunostaining) located within the hippocampal fornices and corpus callosum. There was no evidence of skull fracture, hematomas, or previous cerebral infarctions. In a subsequent study, Blumbergs et al. (1996) compared six mild and six severe TBI (GCS 2–8) cases. Whereas damaged axons in the fornices and corpus callosum were found in both groups, the severe TBI group also had axonal injury in the cerebellar peduncles. Furthermore, the severe TBI group showed evidence of vascular damage but the mTBI group did not.

Animal brain A nonhuman primate model neuropathologic study somewhat relevant to nonblast mTBI was used by Gennarelli et al. (1982). Primates were subjected to very rapid head accelerations in an attempt to simulate a noncontact impact pulse in one of three directions to produce various loss of consciousness (LOC). With this model the three grades of DAI described can be produced (Adams et al., 1989). In two subgroups (head acceleration in sagittal and coronal plane) of these animals, coma, lasting less than 15 minutes and 16–119 minutes respectively, is described. Those with LOC interval less than 30 minutes could, by the definition used in humans, be considered mTBI. In those animals with less

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than 15 minutes and three of those in the 16 minutes to 2 hours group, no evidence of classically described DAI (Adams et al., 1982) was found. DAI was more evident in animals with longer LOC periods and progressively increased the longer the period of unconsciousness (Gennarelli et al., 1982). Coma lasting more than 6 hours was not found in animals whose heads were rotated in the sagittal or oblique plane but only in the lateral plane and produced severe DAI of grade 3 (Gennarelli et al., 1982; Adams et al., 1989). Loss of consciousness at intermediate durations resulted in intermediate grade of DAI. Several investigators (Smith et al., 1999; Chen et al., 1999) subjected miniature swine under isoflurane anesthesia to noncontact impact type acceleration pulses similar to Gennarelli et al. (1982) to induce brain injury. The gas anesthetic was withdrawn 10 seconds prior to load exposure. All animals began to awaken 15 minutes following injury and were able to ambulate within 1 hour but had slightly sluggish responses to sensory stimuli for up to 8 hours post-trauma. The short recovery time (