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Appendix J
Contemporary Methods for Assessing
Behind-Armor Blunt Trauma in Live Animals
This appendix provides an overview of behind-armor blunt trauma
(BABT) assessment methodologies.73 Several research groups from at least four
nations have adopted a pig model for live-animal testing, and a fairly standard
instrumentation package has evolved. This was agreed upon by a meeting in
Koblenz in 1998 involving the principal countries involved in this work (Mayorga
et al., 2010). The protocols for these studies require animals to be anesthetized
and to have approval from animal care and welfare review boards.
Pigs weighing up to 60 kg are used because of their availability, thorax
size that mimics human anatomy, and ease of instrumentation. Each pig is
intubated and properly infused with supportive electrolytes. Respiration, blood
pressure, electrocardiogram, blood oxygen saturation, and temperature are
monitored. Most experiments used the North Atlantic Treaty Organization
(NATO) 7.62 mm projectile fired at full charge from 10 meters at a velocity of
approximately 820 m/sec. The pigs are shot over the eighth rib. The rib cage is
instrumented with accelerometers and pressure sensors close to the impact point.
(This is a major protocol defect because the placements of pressure transducers
are affected by motion sensor saturation.) Each animal is examined by autopsy
using a standard procedure including photography, with specific attention directed
to the thoracic organs and the presence of trauma to the abdominal viscera.
This is the protocol followed by the NATO group and is not a protocol
that will allow observations of pressure waves or measurement of pressure
transmission and pathophysiology of organs such as brain, heart, and intestines.
The protocol for most of the NATO experiments does not allow observing effects
beyond the acute stage of 30 min. Thus, to answer the question of remote damage
from blunt trauma a more extensive protocol is needed. Essential elements of such
a protocol are shown in Figure J-1.
73
The committee is grateful to Miriam D. Budinger and Robert Smith of Lawrence
Berkley National Laboratory, who provided information for the preparation of this appendix.
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FIGURE J-1 Comprehensive protocol for live-animal live-fire tests.
COMPREHENSIVE PROTOCOL FOR ASSESSING DAMAGE TO
TISSUES REMOTE FROM THE SITE OF BLUNT TRAUMA
It is important to maintain surveillance of animals for as long as feasible
after the live-fire exposure. Previous studies under NATO protocols lasted for a
little as 30 min. Other studies have observed animals up to 8 hr before
termination. The humane guidance has been to terminate the animals before they
recover from the anesthesia, and this is recommended if the animals have received
substantial trauma. Under conditions that produce minimal trauma—for example,
EKG, EEG, and respirations—and no hemoptisis, permission to observe the
animals longer term should be pursued, as the resulting medical information
would be crucial for development of personnel protective armor.
Theory and model studies cannot predict long-term consequence for blunt
trauma to live organisms.
Pathology
Conventional gross and microscopic histopathology studies should be
routine at the termination of animal studies. Measurements of blood-brain barrier
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or small vessel permeability changes are extremely important according to
original studies by Suneson et al. (1987), wherein Evans blue dye injected before
live-fire tests showed small vessel leakage at autopsy. Important additions to the
study of the brain are the search for T-tau hyperphosphorylated protein as well as
measurements of c-Fos and c-Myc expression and deposition of -APP (Blennow
et al., 1995; Blennow et al., 2010; Säljö et al., 2002). Other important assays for
nerve damage include glial fibrillar acidic protein and fibrillar light protein. The
timing for these measurements after trauma is important as previous studies might
have waited too long (e.g., 7 days) to see some chemical manifestation of nerve
damage from spinal fluid samples.
Detection of Brain Pathology from Transmitted Shock Pressures in Animals
Perhaps of greatest importance is the need for a method that can detect one
or more of the following subtle and often microscopic changes in vivo through
noninvasive imaging for large animals.
Early epidural and subdural hematomas less than 5 mm wide at the
cortical-skull boundary;
Early signs of edema, such as flattening of the sulci, changes in MR
T1, changes in acoustic reflection (impedance), microwave reflective
power (dielectric coefficient), or electrical activity (impedance,
potential difference dynamics);
Axonal damage in the brain stem and corpus callosum with local
edema and water diffusion changes;
Brain surface contusion before frank edema occurs;
Brain blood flow changes;
Local brain blood volume changes due to local vascular dilatation or
vascular tears at the cortical-skull boundary (epidural and subdural
hematomas less than 5 mm wide).
Quantification of Pressure Wave Dispersion
Two general categories for measurement are pressure wave dispersion
imaging and pressure transducer implantation. The early imaging studies included
the spark gap optical methods of Harvey and McMillen (1947) and
cineradiography applied to ballistic trauma to the head (Butler et al., 1945) and to
nerve and bone (Puckett et al., 1946). Modern instrumentation for
cineradiography, while expensive to deploy in live-fire tests in live large animals,
is an important approach. Quantification of pressure distribution does require
more invasive instrumentation. While straightforward for low frequency
measurements, instrumentation for very high frequency response is needed for
these applications, and miniaturization is essential for minimizing trauma during
implantation. In addition the pressure sensor must be insensitive to accelerations
and temperature changes. Successful recordings of pressures in the brain have
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been reported in small animals by Chavko et al. (2007), who used a miniature
fiberoptic transducer implanted in the brain and invented by Pinet et al. (2005).
The probe is an order of magnitude smaller than conventional piezoelectric
sensors and is able to withstand harsh environments (Pinet et al., 2005).
Electrical Pathophysiology
Electroencephalography and electrical impedance tomography are two
techniques that might be used to assess central nervous system integrity through
measurement of electrical properties both during the acute phase of ballistic
trauma and during posttrauma intervals up to months. Both approaches require
sensitive instruments and are plagued by electrode coupling noise. However, in
previously successful large- and small-animal experiments, EEG measurements
and impedance measurements (Drobin et al., 2007; Cooper, 1996; Olsson et al.,
2006; Klein and Krop-Van Gastel, 1993) have shown the kinetics of brain
physiologic response to blunt trauma to the chest.
MRI Imaging
Of the four methods that have known efficacy in the examination of the
brain in vivo (EEG, X-ray CT, PET, and MRI), MRI is the one that can provide
noninvasive information specific to most of the relevant pathologies.
MRI can provide a wealth of information regarding organ changes
associated with ballistic trauma to the body, as has already been shown in studies
of blast-injured veterans (Van Boven et al., 2009). Specific capabilities for
noninvasive measurements are as follows.
Brain contusion. Edema is an expected early sign of contusion. It will
appear as a bright signal on T2-weighted or fluid attenuation inversion
recovery MRI. T1-weighted protocols might give as sensitive a
diagnosis as other protocols.
Brain edema. Edema resulting from vascular compromise (i.e., air
emboli from lung damage), pressure impulse transmitted from the
periphery to the brain, or ischemic damage from other causes can be
detected by MRI diffusion weighted imaging sequences by fluid
attenuation inversion recovery, and possibly by T1-weighted
protocols.
Hemorrhage. Early signs of hemorrhage usually occur due to tears in
the tributary surface veins that bridge the brain surface to the dural
venous sinus. T2-weighted MRI can show the accumulation of blood
as a bright signal initially, with an evolution to a dark signal in 2 to 3
days and back again to a bright signal within the first 2 weeks (Taber
et al., 2003).
Neuronal disruption. Neural axon injury might be the most subtle yet
the most important pathology that requires early imaging for diagnosis
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(Mayorga, 1997). Experience has shown that this pathology might be
seen in the corpus callosum and brain stem. Diffusion weighted
imaging and T1-weighted protocols might be of extreme importance in
this diagnosis (Huisman, 2010). But the choice of MR protocol is
important here as it has been shown that susceptibility-weighted MRI
depicts significantly more small hemorrhagic lesions than does
conventional gradient echo MRI and therefore has the potential to
improve the diagnosis of diffuse axonal injury (Tong et al., 2003).
The MRI system should be able to perform the above imaging studies in
addition to standard structural sequences, including gradient echo as well as spin
echo approaches to achieve the desired physiologic contrast signals.
Instrumentation availability and costs vary widely from a permanent
magnet system for small animals at less than $0.5 million to elaborate systems
that combine magnetic resonance with PET at over $2 million. Most studies can
be enabled through collaboration with medical studies.
PET and SPECT Imaging
Metabolic and quantitative flow imaging using positron emission
tomography or single photon tomography can provide sensitive metrics of
pathological changes in most of the body organs of medium to large animals. The
methods are noninvasive and can be repeated over the course of hours or days.
Whereas PET and SPECT are readily available in medical centers, not all
experimentalists will have these instruments and the required radioisotopes
available, particularly for small animal studies. The spatial resolution in
instruments designed for animal studies can be 2 mm or less. Normally the spatial
resolution for large animals and human subjects is 5 to 6 mm.
The tracers available allow studies of blood flow, glucose uptake
(commonly interpreted as cerebral metabolism), dopamine transporters and
receptors, muscarinic system activity, and blood-brain permeability. Recent
human studies in boxers showed patterns of hypometabolism using as a marker
the accumulation of F-18 deoxyglucose, but one must be careful not to interpret
hypometabolism when the reason for less apparent tracer uptake is tissue atrophy
rather than a decrease in the metabolic uptake mechanism (Provenzano et al.,
2010). Thus, metabolic and neurochemical studies should be accompanied by MR
anatomical studies and, in some cases, by flow studies since compromised flow
will lead to an apparent decrease in uptake, particularly when studying the
neurochemical systems.
PET and SPECT instrumentation for small animal studies is available
from a number of vendors. Large animal studies can be accomplished through
collaborators at medical institutions where the requisite approvals for use of
radionuclides are already in place.
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Ultrasound Brain Blood Flow Measurements
Measurements of blood flow in the brain basal arteries and the carotids by
transcranial Doppler are surrogates for estimating cerebral vascular resistance and
are effective methods for detection of vasospasm associated with abnormally high
velocities (Jaffres et al., 2005; Visocchi et al., 2002). These measurements rely on
some skill of the operator. Vascular spasm can occur late after brain injury and
this will result in a change in the flow characteristics with eventual change in
electrical impedance (Armonda et al., 2006; Kochanowicz et al., 2006; Oertel et
al., 2005; Fritz et al., 2005; Harting et al., 2010).
Ultrasound instrumentation is generally more available than the other
radiological imaging systems for human studies. Specialized small animal
systems are now available to the researcher.
Short- and Long-Term Cardiac Responses
During the first hour after blunt trauma to the chest, temporary cardiac
arrhythmias have been observed in previous live-fire tests on animals protected by
vests. The longer term as well as short term changes in heart contractions are
unknown but will be important to determine for current and future protective vest
designs. Thus in some experiments direct and continuous measurements of
intrathoracic cardiac and aortic pressures and dimensions are recommended using
radiotelemetry. These techniques are well known and can be reliably implemented
in unrestrained animals.
GLOSSARY
Acoustic impedance. A material property that relates to its resistance to the
propagation of sound pressure. It is the square root of the product of the tissue
modulus of elasticity and the tissue density. The equivalent definition is
impedance equals the product of tissue density and the speed of sound in that
tissue (e.g., 1,480 m/sec for solid tissue and water, 5,900 m/sec in steel, 9,900
m/sec in alumina).
Atmospheric pressure. The pressure exerted at sea level from atmospheric gases
is measured as 14.7 pounds per square inch or, in SI units, as about 100
kilopascals (kPa).
Backface deformation (BFD). The extent to which the back material of the body
armor is displaced by low- or high-velocity ballistic impacts.
Behind-armor blunt trauma (BABT). When body armor is impacted by a high-
velocity bullet but not perforated, some of the energy of the bullet will enter the
body. The interaction of this energy with the thoracic region of the human body
may or may not cause an injury. If injury is caused, it is referred to as behind-
armor blunt trauma (BABT). In the past, it was considered as trauma to the ribs
and lungs but now includes trauma anywhere in the body.
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Cineradiography. Method for acquiring x-rays at very rapid rate so that the
dynamics of a process can be recorded when tissue opaqueness does not allow
rapid light photography.
Decibel. A measure of the amount of some physical parameter relative to a
reference base. For blast pressure it is force per area (newtons/m2), and the ratio
of the measured pressure to the base value for human perception of sound is so
great that the decibel is reported as 20 times the logarithm of the ratio. Sound
intensity is power per area (watts/m2) and the decibel is 10 times the logarithm of
the ratio. Conversion of decibel sound pressure level, dB(SPL), to pascal, (Pa)
units is
(Pa) = 2 × 10-5 × 10 dB/20
where the factor 2 × 10-5 is the minimum pressure for human sound detection in
newtons/m2, or pascals. Thus the pressure for normal conversation at 60 dB is
0.02 Pa and for a passing truck at 100 dB is 2 Pa. Pressures from behind armor are
in the range of 500 kPa, or 208 dB.
Kinetic energy. The energy associated with the velocity and mass of a body
(projectile). It is ½ mass × (velocity)2. The unit is the joule (J). Projectiles deliver
033 to 13 kJ depending on the bullet used.
Magnetic resonance imaging (MRI). An imaging method that shows tissue
anatomy based on water content and local environment characteristics. Diffusion-
weighted imaging (DWI) and diffusion tensor imaging (DTI) are forms of MRI
that allow definition of structural properties of tissue based on water diffusion
directional preferences.
National Institute of Justice (NIJ) Standard. The NIJ 0101.04 standard
stipulates the maximum deformation a soft armor vest can undergo without
penetration is 44 mm as measured in a clay substrate after a live fire test of the
armor.
Overpressure. The blast pressure from a bomb, artillery discharge, bazooka, or
other explosion. Overpressure is defined as the pressure from the blast over
atmospheric pressure; it is usually followed by an underpressure.
Pascal. Unit for pressure equivalent to 1 newton/m2 (1 pascal is 0.0001
atmospheric pressure). A gigapascal (GPa) is a unit of pressure equal to a billion
pascals. A kilopascal (kPa) is a unit of pressure equal to a 1,000 pascals (100 kPa
is 1 atmosphere of pressure).
Positron emission tomography (PET). An imaging method that provides
quantative information on metabolism, flow, and neurochemical receptors using
radionuclides usually obtained from a cyclotron. The method is useful for imaging
metabolism and function in the brain, lungs, and other organs.
Power. Energy per time. Unit is the watt, which is 1 Joule/sec.
Pressure. Force per area (newton /m2 = pascal).
Single photon emission tomography (SPECT). This is an imaging method
similar to PET; however, it uses radionuclides generally obtainable without the
need for a cyclotron. The method is useful for imaging metabolism and function
in brain, lungs, and other organs.
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Strain. The relative change in dimension ∆L/L in response to a stress, where L=
is a length measure.
Stress. The force per area applied to a material. Units are newton/m2 and are
usually reported as pascals.
Stress waves. Compression waves in a material due to an impulse or sudden load
change.
Underpressure. The negative pressure relative to atmospheric pressure
experienced by personnel following the blast pressure from an explosion.
Young’s modulus. A measure of the stiffness of elastic material, it is defined as
the ratio of the uniaxial stress or force per area over the strain or the fractional
length change in the direction of the stress. The dimension is given as pascals or
pounds per square inch (psi). For example, steel has a Young’s modulus of 200
GPa, Kevlar of about 100 GPa, and polyethylene of 3 GPa.
7.62 mm x 51 mm bullet. A rifle bullet similar to the .30-06 bullet in dimensions
and performance. Another model is the 7.62 mm × 61 mm bullet.
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