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One of the challenges associated with conducting experiments in animal models of traumatic spinal cord injury (SCI) is inducing a consistent injury with minimal variability in the degree of tissue damage and resultant behavioral and biochemical outcomes. We evaluated how the variability in morphometry of the spinal cord and surrounding cerebrospinal fluid (CSF) contributes to the variability in behavioral and histological outcomes in our porcine model of SCI. Using intraoperative ultrasound imaging, spinal cord morphometry was assessed in seven Yucatan minipigs undergoing a weight-drop T10 contusion-compression injury. Bivariate and multi-variate analysis and modeling were used to identify native morphometrical determinants of interanimal variability in histological and behavioral outcomes. The measured biomechanical impact parameters did not correlate with the histological measures or hindlimb locomotor behavior (Porcine Thoracic Injury Behavior Scale). In contrast, clear associations were revealed between CSF layer morphometry and the amount of white matter and tissue sparing. Specifically, the dorsoventral diameter of the dural sac and ventral CSF space were strong predictors of behavioral and histological outcome and together explained ≥95.0% of the variance in these parameters. In addition, a dorsoventral diameter of the spinal cord less than 5.331 mm was a strong contributing factor to poor behavioral recovery over 12 weeks. These results indicate that interanimal variability in cord morphometry provides a potential biological explanation for the observed heterogeneity in histological and behavioral outcomes. Such knowledge is helpful for appropriately balancing experimental groups, and/or varying impact parameters to match cord and CSF layer dimensions for future studies.

Background CT is considered the best method for vertebral fracture detection clinically, but its efficacy in laboratory studies is unknown. Therefore, our objective was to determine the sensitivity, precision, and specificity of high-resolution CT imaging compared to detailed anatomic dissection in an axial compression and lateral bending cervical spine biomechanical injury model. Methods 35 three-vertebra human cadaver cervical spine specimens were impacted in dynamic axial compression (0.5 m/s) at one of three lateral eccentricities (low 5% of the spine transverse diameter, middle 50%, high 150%) and two end conditions (19 constrained lateral translation and 16 unconstrained). All specimens were imaged using high resolution CT imaging (246 μm). Two clinicians (spine surgeon and neuroradiologist) diagnosed the vertebral fractures based on 34 discrete anatomical structures using both the CT images and anatomical dissection. Findings The sensitivity of CT was highest for fractures of the facet joint (59%) and vertebral endplate (57%), and was lowest for pedicle (13%) and lateral mass fractures (23%). The precision of CT was highest for spinous process fractures (83%) and lowest for pedicle (21%), uncinate process and lateral mass (both 23%) fractures. The specificity of CT exceeded 90% for all fractures. The Kappa value between the two reviewers was 0.52, indicating moderate agreement. Interpretation In this in vitro cervical spine injury model, high resolution CT scanning missed many fractures, notably those of the lateral mass and pedicle. This finding is potentially important clinically, as the integrity of these structures is important to clinical stability and surgical fixation planning.

After acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarachnoid space and become compressed by the surrounding dura. In a porcine model of SCI, we performed a duraplasty to expand the subarachnoid space around the injured spinal cord and evaluated how this influenced acute intraparenchymal hemodynamic and metabolic responses, in addition to histological and behavioral recovery. Female Yucatan pigs underwent a T10 SCI, with or without duraplasty. Using microsensors implanted into the spinal cord parenchyma, changes in blood flow (ΔSCBF), oxygenation (ΔPO

Bone, 125, ISSN:8756-3282

Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint. Compared to sham controls, rats with rTBI displayed progressive impairment in impulsive choice. Histological analyses revealed reduced dopaminergic innervation from the ventral tegmental area to the olfactory tubercle, consistent with altered impulsivity neurocircuitry. Consistent with diffuse axonal injury generated by CHIMERA, white matter inflammation, tau immunoreactivity and degeneration were observed in the optic tract and corpus callosum. Finally, pronounced grey matter microgliosis was observed in the olfactory tubercle. Our results provide insight into the mechanisms by which rTBI leads to post-traumatic psychiatric-like symptoms in a novel rat TBI platform.

Background Head-first impacts with an aligned cervical spine cause some of the most severe types of injuries due to the risk of fractures and associated spinal cord injury. Sports, such as football, mountain biking and horseback riding, contribute to the incidence of spinal cord injury but there is potential to reduce the risk of these injuries through a helmet-mounted device. Methods A novel device, the Pro-Neck-Tor mechanism, was incorporated into a commercial football helmet and tested in head-first impact experiments. The Pro-Neck-Tor connects an inner and outer helmet shell, which upon head-first impact of a certain load, induces motion of the head away from the path of the following torso. Impacts were performed onto three impact surface angles with a flexion-inducing Pro-Neck-Tor mechanism. Findings Based on averaged data, the Pro-Neck-Tor provided a significant and consistent reduction in peak compressive neck forces compared to the unmodified football helmet in the conditions tested. In some impact conditions, the Pro-Neck-Tor increased the peak sagittal plane neck bending moments and impulse over that observed for the unmodified helmet. Interpretation The Pro-Neck-Tor with flexion escape is capable of lowering axial neck forces in head-first impacts compared to a conventional helmet by guiding the cervical column away from an aligned posture and into an eccentric loading scenario which published studies suggests frequently leads to no injury or to a less severe injury. Continued development and testing of the device are needed to optimize the altered neck loading and to drive the design toward a commercial configuration.

Although spinal cord deformation is thought to be a predictor of injury severity, few researchers have investigated dynamic cord deformation, in vivo, during impact. This is needed to establish correlations among impact parameters, internal cord deformation, and histological and functional outcomes. Relying on surface deformations alone may not sufficiently represent spinal cord deformation. The objective of this study was to develop a high-speed fluoroscopic method of tracking the surface and internal cord deformations of rat spinal cord during experimental cord injury. Two radio-opaque beads were injected into the cord at C5/6 in the dorsal and ventral white matter. Four additional beads were glued to the surface of the cord. Dynamic bead displacement was tracked during a dorsal impact (130 mm/sec, 1 mm depth) by high-speed radiographic imaging at 3000 FPS, laterally. The internal spinal cord beads displaced significantly more than the surface beads in the ventral direction (1.1-1.9 times) and more than most surface beads in the cranial direction (1.2-1.5 times). The dorsal beads (internal and surface) displaced more than the ventral beads during all impacts. The bead displacement pattern implies that the spinal cord undergoes complex internal and surface deformations during impact. Residual displacement of the internal beads was significantly greater than that of the surface beads in the cranial-caudal direction but not the dorsoventral direction. Finite element simulation confirmed that the additional bead mass likely had little effect on the internal cord deformations. These results support the merit of this technique for measuring in vivo spinal cord deformation.

During axial impact compression of the cervical spine, injury outcome is highly dependent on initial posture of the spine and the orientation, frictional properties and stiffness of the impact surface. These properties influence the “end condition” the spine experiences in real-world impacts. The effect of end condition on compression and sagittal plane bending in laboratory experiments is well-documented. The spine is able to escape injury in an unconstrained flexion-inducing end condition (e.g. against an angled, low friction surface), but when the end condition is constrained (e.g. head pocketing into a deformable surface) the following torso can compress the aligned spine causing injury. The aim of this study was to determine whether this effect exists under combined axial compression and lateral bending. Over two experimental studies, twenty-four human three vertebra functional spinal units were subjected to controlled dynamic axial compression at two levels of laterally eccentric force and in two end conditions. One end condition allowed the superior spine to laterally rotate and translate (T-Free) and the other end condition allowed only lateral rotation (T-Fixed). Spine kinetics, kinematics, injuries and occlusion of the spinal canal were measured during impact and pre- and post-impact flexibility. In contrast to typical spine responses in flexion-compression loading, the cervical spine specimens in this study did not escape injury in lateral bending when allowed to translate laterally. The specimen group that allowed lateral translation during compression had more injuries at high laterally eccentric force, saw greater peak canal occlusions and post-impact flexibility than constrained specimens.

In contrast to sagittal plane spine biomechanics, little is known about the response of the cervical spine to axial compression with lateral eccentricity of the applied force. This study evaluated the effect of lateral eccentricity on the kinetics, kinematics, canal occlusion, injuries, and flexibility of the cervical spine in translationally constrained axial impacts. Eighteen functional spinal units were subjected to flexibility tests before and after an impact. Impact axial compression was applied at one of three lateral eccentricity levels based on percentage of vertebral body width (low = 5%, medium = 50%, high = 150%). Injuries were graded by dissection. Correlations between intrinsic specimen properties and injury scores were examined for each eccentricity group. Low lateral force eccentricity produced predominantly bone injuries, clinically recognized as compression injuries, while medium and high eccentricity produced mostly contralateral ligament and/or disc injuries, an asymmetric pattern typical of lateral loading. Mean compression force at injury decreased with increasing lateral eccentricity (low = 3098 N, medium = 2337 N, and high = 683 N). Mean ipsilateral bending moments at injury were higher at medium (28.3 N·m) and high (22.9 N·m) eccentricity compared to low eccentricity specimens (0.1 N·m), p

Mild traumatic brain injuries are typically caused by nonpenetrating head impacts that accelerate the skull and result in deformation of the brain within the skull. The shear and compressive strains caused by these deformations damage neural and vascular structures and impair their function. Accurate head acceleration measurements are necessary to define the nature of the insult to the brain. A novel murine head tracking system was developed to improve the accuracy and efficiency of kinematic measurements obtained with high-speed videography. A three-dimensional (3D)-printed marker carrier was designed for rigid fixation to the upper jaw and incisors with an elastic strap around the snout. The system was evaluated by impacting cadaveric mice with the closed head impact model of engineered rotational acceleration (CHIMERA) system using an energy of 0.7 J (5.29 m/s). We compared the performance of the head-marker system to the previously used skin-tracking method and documented significant improvements in measurement repeatability (aggregate coefficient of variation (CV) within raters from 15.8 to 1.5 and between raters from 15.5 to 1.5), agreement (aggregate percentage error from 24.9 to 8.7), and temporal response (aggregate temporal curve agreement from 0.668 to 0.941). Additionally, the new system allows for automated software tracking, which dramatically decreases the analysis time required (74% reduction). This novel head tracking system for mice offers an efficient, reliable, and real-time method to measure head kinematics during high-speed impacts using CHIMERA or other rodent or small mammal head impact models.

In this work, we quantify the neck's involvement in stabilizing the head during falls in older adults to avoid head impacts. We tracked kinematics of 12 real-world backward falls in long-term care captured on video, where head impact was avoided. We estimated dynamic spring-dashpot parameters of the neck and hip representing active muscle activity and passive tissue structures. Neck stiffness, damping, and target posture averaged 24.00±6.17Nm/rad, 0.38±0.16Nms/rad, and 76.2±14.7° flexion respectively. The stiffness and target posture suggest that residents actively contracted their neck muscles to maintain the head upright. Our results shed light on the importance of neck strength for avoiding head impact during a fall.Clinical Relevance-Falls account for 80% of traumatic brain injuries in adults 65+ years. While upper limb bracing can reduce the risk of head impacts during a fall in young adults, this protective response is less effective in older adults living in longterm care. Understanding how the neck and torso musculature are used to avoid head impact can guide the design of therapeutic exercise programs and assistive or protective devices.

Drivers often react to an impending collision by bracing against the steering wheel. The goal of the present study was to quantify the effect of bracing on neck muscle activity and head/torso kinematics during low-speed front and rear impacts. Eleven seated subjects (3F, 8 M) experienced multiple sled impacts (Δv = 0.77 m/s; apeak = 19.9 m/s2, Δt = 65.5 ms) with their hands on the steering wheel in two conditions: relaxed and braced against the steering wheel. Electromyographic activity in eight neck muscles (sternohyoid, sternocleidomastoid, splenius capitis, semispinalis capitis, semispinalis cervicis, multifidus, levator scapulae, and trapezius) was recorded unilaterally with indwelling electrodes and normalized by maximum voluntary contraction (MVC) levels. Head and torso kinematics (linear acceleration, angular velocity, angular rotation, and retraction) were measured with sensors and motion tracking. Muscle and kinematic variables were compared between the relaxed and braced conditions using linear mixed models. We found that pre-impact bracing generated only small increases in the pre-impact muscle activity (

Cervical spine injuries often happen in dynamic environments (e.g., sports and motor vehicle crashes) where individuals may be moving their head and neck immediately prior to impact. This motion may reposition the cervical vertebrae in a way that is dissimilar to the upright resting posture that is often used as the initial position in cadaveric studies of catastrophic neck injury. Therefore our aim was to compare the "neutral" cervical alignment measured using fluoroscopy of 11 human subjects while resting in a neutral posture and as their neck passed through neutral during the four combinations of active flexion and extension movements in both an upright and inverted posture. Muscle activation patterns were also measured unilaterally using surface and indwelling electromyography in 8 muscles and then compared between the different conditions. Overall, the head posture, cervical spine alignment and muscle activation levels were significantly different while moving compared to resting upright. Compared to the resting upright condition, average head postures were 6-13° more extended, average vertebral angles varied from 11° more extended to 10° more flexed, and average muscle activation levels varied from unchanged to 10% MVC more active, although the exact differences varied with both direction of motion and orientation. These findings are important for ex vivo testing where the head and neck are statically positioned prior to impact - often in an upright neutral posture with negligible muscle forces - and suggest that current cadaveric head-first impact tests may not reflect many dynamic injury environments.

Hip fractures pose a major health problem throughout the world due to their devastating impact. Current theories for why these injuries are so prevalent in the elderly point to an increased propensity to fall and decreases in bone mass with ageing. However, the fracture mechanisms, particularly the stress and strain conditions leading to bone failure at the hip remain unclear. Here, we directly examined the cortical bone from clinical intra-capsular hip fractures at a microscopic level, and found strong evidence of compression induced failure in the superior cortex. A total of 143 sections obtained from 24 femoral neck samples that were retrieved from 24 fracturing patients at surgery were examined using laser scanning confocal microscopy (LSCM) after fluorescein staining. The stained microcracks showed significantly higher density in the superior cortex than in the inferior cortex, indicating a greater magnitude of strain in the superior femoral neck during the failure-associated deformation and fracture process. The predominant stress state for each section was reconstructed based on the unique correlation between the microcrack pattern and the stress state. Specifically, we found clear evidence of longitudinal compression and buckling as the primary failure mechanisms in the superior cortex. These findings demonstrate the importance of microcrack analysis in studying clinical hip fractures, and point to the central role of the superior cortex failure as an important aspect of the failure initiation in clinical intra-capsular hip fractures.

Despite efforts to simulate the in vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex vivo, the viscoelastic behavior of in vivo and ex vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex vivo and in vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex vivo samples experienced a higher stress and greater relaxation than in vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1–1 s). The results of this study underscore the necessity of utilizing material models developed from in vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in vivo model in future high-resolution finite element modeling efforts. Statement of Significance Neural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a living animal (in vivo response). Therefore, this study directly compared the mechanical response of ex vivo and in vivo samples to quantify these differences for the first time. This will allow researchers to draw more accurate conclusions about spinal cord injuries based on ex vivo data (which are easier to obtain) and emphasizes the importance of future in vivo experimental animal work.

The limitations of areal bone mineral density measurements for identifying at-risk individuals have led to the development of alternative screening methods for hip fracture risk including the use of geometrical measurements from the proximal femur and subject specific finite element analysis (FEA) for predicting femoral strength, based on quantitative CT data (qCT). However, these methods need more development to gain widespread clinical applications. This study had three aims: To investigate whether proximal femur geometrical parameters correlate with obtained femur peak force during the impact testing; to examine whether or not failure of the proximal femur initiates in the cancellous (trabecular) bone; and finally, to examine whether or not surface fracture initiates in the places where holes perforate the cortex of the proximal femur. We found that cortical thickness around the trochanteric-fossa is significantly correlated to the peak force obtained from simulated sideways falling (R 2 = 0.69) more so than femoral neck cortical thickness (R 2 = 0.15). Dynamic macro level FE simulations predicted that fracture generally initiates in the cancellous bone compartments. Moreover, our micro level FEA results indicated that surface holes may be involved in primary failure events.

MINI: Identifying fracture is important for understanding vertebral mechanics. Isolated cadaveric thoracolumbar vertebrae were compressed, and surface strains were measured using digital image correlation. Fracture locations from video analysis were qualitatively similar to the locations of high compressive strains and local damage occurred before the maximum force was reached. STUDY DESIGN Ex vivo compression experiments on isolated cadaveric vertebrae. OBJECTIVE To qualitatively compare the fracture locations identified in video analysis with the locations of high compressive strain measured with digital image correlation (DIC) on vertebral bodies and to evaluate the timing of local damage to the cortical shell relative to the global yield force. SUMMARY OF BACKGROUND DATA In previous ex vivo experiments, cortical bone fracture has been identified using various methods including acoustic emission sensors, strain gages, video analysis, or force signals. These methods are, however, limited in their ability to detect the location and timing of fracture. We propose use of DIC, a noncontact optical technique that measures surface displacement, to quantify variables related to damage. METHODS Isolated thoracolumbar human cadaveric vertebral bodies (n = 6) were tested in compression to failure at a quasi-static rate, and the force applied was measured using a load cell. The surface displacement and strain were measured using DIC. Video analysis was performed to identify fractures. RESULTS The location of fractures identified in the video corresponded well with the locations of high compressive strain on the bone. Before reaching the global yield force, more than 10% of the DIC measurements reached a minimum principal strain of 1.0%, a previously reported threshold for cortical bone damage. CONCLUSION DIC measurements provide an objective measure that can be used to identify the location and timing of fractures during ex vivo vertebral experiments. This is important for understanding fracture mechanics and for validating vertebral computational models that incorporate failure. LEVEL OF EVIDENCE N /A.

In the military environment, injured soldiers undergoing medical evacuation via helicopter or mine-resistant ambush-protected vehicle (MRAP) are subjected to vibration and shock inherent to the transport vehicle. We conducted the present study to assess the consequences of such vibration on the acutely injured spinal cord. We used a porcine model of spinal cord injury (SCI). After a T10 contusion-compression injury, animals were subjected to 1) no vibration (n = 7-8), 2) whole body vibration at frequencies and amplitudes simulating helicopter transport (n = 8), or 3) whole body vibration simulating ground transportation in an MRAP ambulance (n = 7). Hindlimb locomotor function (using Porcine Thoracic Injury Behavior Scale [PTIBS]), Eriochrome Cyanine histochemistry and biochemical analysis of inflammatory and neural damage markers were analyzed. Cerebrospinal fluid (CSF) expression levels for monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-8, and glial fibrillary acidic protein (GFAP) were similar between the helicopter or MRAP group and the unvibrated controls. Spared white/gray matter tended to be lower in the MRAP-vibrated animals than in the unvibrated controls, especially rostral to the epicenter. However, spared white/gray matter in the helicopter-vibrated group appeared normal. Although there was a relationship between the extent of sparing and the extent of locomotor recovery, no significant differences were found in PTIBS scores between the groups. In summary, exposures to vibration in the context of ground (MRAP) or aeromedical (helicopter) transportation did not significantly impair functional outcome in our large animal model of SCI. However, MRAP vibration was associated with increased tissue damage around the injury site, warranting caution around exposure to vehicle vibration acutely after SCI.

Traumatic brain injury (TBI) is a leading cause of death and disability in modern societies. Diffuse axonal and vascular injury are nearly universal consequences of mechanical energy impacting the head and contribute to disability throughout the injury severity spectrum. CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a non-surgical, impact-acceleration model of rodent TBI that reliably produces diffuse axonal injury characterized by white matter gliosis and axonal damage. At impact energies up to 0.7 joules, which result in mild TBI in mice, CHIMERA does not produce detectable vascular or grey matter injury. This study was designed to expand CHIMERA's capacity to induce more severe injuries, including vascular damage and grey matter gliosis. This was made possible by designing a physical interface positioned between the piston and animal's head to allow higher impact energies to be transmitted to the head without causing skull fracture. Here, we assessed interface-assisted single CHIMERA TBI at 2.5 joules in wild-type mice using a study design that spanned 6 h–60 d time points. Injured animals displayed robust acute neurological deficits, elevated plasma total tau and neurofilament-light levels, transiently increased proinflammatory cytokines in brain tissue, blood-brain barrier (BBB) leakage and microstructural vascular abnormalities, and grey matter microgliosis. Memory deficits were evident at 30 d and resolved by 60 d. Intriguingly, white matter injury was not remarkable at acute time points but evolved over time, with white matter gliosis being most extensive at 60 d. Interface-assisted CHIMERA thus enables experimental modeling of distinct endophenotypes of TBI that include acute vascular and grey matter injury in addition to chronic evolution of white matter damage, similar to the natural history of human TBI.

Computational models of the human brain are widely used in the evaluation and development of helmets and other protective equipment. These models are often attempted to be validated using cadaver tissue displacements despite studies showing neural tissue degrades quickly after death. Addressing this limitation, this study aimed to develop a technique for quantifying living brain motion in vivo using a closed head impact animal model of traumatic brain injury (TBI) called CHIMERA. We implanted radiopaque markers within the brain of three adult ferrets and resealed the skull while the animals were anesthetized. We affixed additional markers to the skull to track skull kinematics. The CHIMERA device delivered controlled, repeatable head impacts to the head of the animals while the impacts were fluoroscopically stereo-visualized. We observed that 1.5 mm stainless steel fiducials (∼8 times the density of the brain) migrated from their implanted positions while neutral density targets remained in their implanted position post-impact. Brain motion relative to the skull was quantified in neutral density target tests and showed increasing relative motion at higher head impact severities. We observed the motion of the brain lagged behind that of the skull, similar to previous studies. This technique can be used to obtain a comprehensive dataset of in vivo brain motion to validate computational models reflecting the mechanical properties of the living brain. The technique would also allow the mechanical response of in vivo brain tissue to be compared to cadaveric preparations for investigating the fidelity of current human computational brain models.

Background: The annual incidence of traumatic brain injury (TBI) in the United States is over 2.5 million, with approximately 3–5 million people living with chronic sequelae. Compared with moderate-severe TBI, the long-term effects of mild TBI (mTBI) are less understood but important to address, particularly for contact sport athletes and military personnel who have high mTBI exposure. The purpose of this study was to determine the behavioural and neuropathological phenotypes induced by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model of mTBI in both wild-type (WT) and APP/PS1 mice up to 8 months post-injury. Methods: Male WT and APP/PS1 littermates were randomized to sham or repetitive mild TBI (rmTBI; 2 × 0.5 J impacts 24 h apart) groups at 5.7 months of age. Animals were assessed up to 8 months post-injury for acute neurological deficits using the loss of righting reflex (LRR) and Neurological Severity Score (NSS) tasks, and chronic behavioural changes using the passive avoidance (PA), Barnes maze (BM), elevated plus maze (EPM) and rotarod (RR) tasks. Neuropathological assessments included white matter damage; grey matter inflammation; and measures of Aβ levels, deposition, and aducanumab binding activity. Results: The very mild CHIMERA rmTBI conditions used here produced no significant acute neurological or motor deficits in WT and APP/PS1 mice, but they profoundly inhibited extinction of fear memory specifically in APP/PS1 mice over the 8-month assessment period. Spatial learning and memory were affected by both injury and genotype. Anxiety and risk-taking behaviour were affected by injury but not genotype. CHIMERA rmTBI induced chronic white matter microgliosis, axonal injury and astrogliosis independent of genotype in the optic tract but not the corpus callosum, and it altered microgliosis in APP/PS1 amygdala and hippocampus. Finally, rmTBI did not alter long-term tau, Aβ or amyloid levels, but it increased aducanumab binding activity. Conclusions: CHIMERA is a useful model to investigate the chronic consequences of rmTBI, including behavioural abnormalities consistent with features of post-traumatic stress disorder and inflammation of both white and grey matter. The presence of human Aβ greatly modified extinction of fear memory after rmTBI.

During traumatic spinal cord injury (SCI), the spinal cord is subject to external displacements that result in damage of neural tissues. These displacements produce complex internal deformations, or strains, of the spinal cord parenchyma. The aim of this study is to determine a relationship between these internal strains during SCI and primary damage to spinal cord gray matter (GM) in an in vivo rat contusion model. Using magnetic resonance imaging and novel image registration methods, we measured three-dimensional (3D) mechanical strain in in vivo rat cervical spinal cord (n = 12) during an imposed contusion injury. We then assessed expression of the neuronal transcription factor, neuronal nuclei (NeuN), in ventral horns of GM (at the epicenter of injury as well as at intervals cranially and caudally), immediately post-injury. We found that minimum principal strain was most strongly correlated with loss of NeuN stain across all animals (R2 = 0.19), but varied in strength between individual animals (R2 = 0.06–0.52). Craniocaudal distribution of anatomical damage was similar to measured strain distribution. A Monte Carlo simulation was used to assess strain field error, and minimum principal strain (which ranged from 8% to 36% in GM ventral horns) exhibited a standard deviation of 2.6% attributed to the simulated error. This study is the first to measure 3D deformation of the spinal cord and relate it to patterns of ensuing tissue damage in an in vivo model. It provides a platform on which to build future studies addressing the tolerance of spinal cord tissue to mechanical deformation.

The spinal cord undergoes physical deformation during traumatic spinal cord injury (TSCI), which results in biological damage. This study demonstrates a novel approach, using magnetic resonance imaging and image registration techniques, to quantify the three-dimensional deformation of the cervical spinal cord in an in vivo rat model. Twenty-four male rats were subjected to one of two clinically relevant mechanisms of TSCI (i.e. contusion and dislocation) inside of a MR scanner using a novel apparatus, enabling imaging of the deformed spinal cords. The displacement fields demonstrated qualitative differences between injury mechanisms. Three-dimensional Lagrangian strain fields were calculated, and the results from the contusion injury mechanism were deemed most reliable. Strain field error was assessed using a Monte Carlo approach, which showed that simulated normal strain error experienced a bias, whereas shear strain error did not. In contusion injury, a large region of dorso-ventral compressive strain was observed under the impactor which extended into the ventral region of the spinal cord. High tensile lateral strains under the impactor and compressive lateral strains in the lateral white matter were also observed in contusion. The ability to directly observe and quantify in vivo spinal cord deformation informs our knowledge of the mechanics of TSCI.

Bone can be viewed as a nano-fibrous composite with complex hierarchical structures. Its deformation and fracture behaviors depend on both the local structure and the type of stress applied. In contrast to the extensive studies on bone fracture under compression and tension, there is a lack of knowledge on the fracture process under shear, a stress state often exists in hip fracture. This study investigated the mechanical behavior of human cortical bone under shear, with the focus on the relation between the fracture pattern and the microstructure. Iosipescu shear tests were performed on notched rectangular bar specimens made from human cortical bone. They were prepared at different angles (i.e. 0°, 30°, 60° and 90°) with respect to the long axis of the femoral shaft. The results showed that human cortical bone behaved as an anisotropic material under shear with the highest shear strength (~50MPa) obtained when shearing perpendicular to the Haversian systems or secondary osteons. Digital image correlation (DIC) analysis found that shear strain concentration bands had a close association with long bone axis with an average deviation of 11.8° to 18.5°. The fracture pattern was also greatly affected by the structure with the crack path generally following the direction of the long axes of osteons. More importantly, we observed unique peripheral arc-shaped microcracks within osteons, using laser scanning confocal microscopy (LSCM). They were generally long cracks that developed within a lamella without crossing the boundaries. This microcracking pattern clearly differed from that created under either compressive or tensile stress: these arc-shaped microcracks tended to be located away from the Haversian canals in early-stage damaged osteons, with ~70% developing in the outer third osteonal wall. Further study by second harmonic generation (SHG) and two-photon excitation fluorescence (TPEF) microscopy revealed a strong influence of the organization of collagen fibrils on shear microcracking. This study concluded that shear-induced microcracking of human cortical bone follows a unique pattern that is governed by the lamellar structure of the osteons.

Little is known about the internal mechanics of the in vivo spinal cord during injury. The objective of this study was to develop a method of tracking internal and surface deformation of in vivo rat spinal cord during compression using radiography. Since neural tissue is radio-translucent, radio-opaque markers were injected into the spinal cord. Two tantalum beads (260 µm) were injected into the cord (dorsal and ventral) at C5 of nine anesthetized rats. Four beads were glued to the lateral surface of the cord, caudal and cranial to the injection site. A compression plate was displaced 0.5 mm, 2 mm, and 3 mm into the spinal cord and lateral X-ray images were taken before, during, and after each compression for measuring bead displacements. Potential bead migration was monitored for by comparing displacements of the internal and glued surface beads. Dorsal beads moved significantly more than ventral beads with a range in averages of 0.57-0.71 mm and 0.31-0.35 mm respectively. Bead displacements during 0.5 mm compressions were significantly lower than 2 mm and 3 mm compressions. There was no statistically significant migration of the internal beads. The results indicate the merit of this technique for measuring in vivo spinal cord deformation. The pattern of bead displacements illustrates the complex internal and surface deformations of the spinal cord during transverse compression. This information is needed for validating physical and finite element spinal cord surrogates and to define relationships between loading parameters, internal cord deformation, and biological and functional outcomes.

Background: After an acute traumatic spinal cord injury (SCI), the spinal cord is subjected to ischemia, hypoxia, and increased hydrostatic pressure which exacerbate further secondary damage and neuronal deficit. The purpose of this pilot study was to explore the use of near infrared spectroscopy (NIRS) for non-invasive and real-time monitoring of these changes within the injured spinal cord in an animal model. NIRS is a non-invasive optical technique that utilizes light in the near infrared spectrum to monitor changes in the concentration of tissue chromophores from which alterations in tissues oxygenation and perfusion can be inferred in real time. Methods: A custom-made miniaturized NIRS sensor was developed to monitor spinal cord hemodynamics and oxygenation noninvasively and in real time simultaneously with invasive, intraparenchymal monitoring in a pig model of SCI. The spinal cord around the T10 injury site was instrumented with intraparenchymal probes inserted directly into the spinal cord to measure oxygen pressure, blood flow, and hydrostatic pressure, and the same region of the spinal cord was monitored with the custom-designed extradural NIRS probe. We investigated how well the extradural NIRS probe detected intraparenchymal changes adjacent to the injury site after alterations in systemic blood pressure, global hypoxia, and traumatic injury generated by a weight-drop contusion. Results: The NIRS sensor successfully identified periods of systemic hypoxia, re-ventilation and changes in spinal cord perfusion and oxygenation during alterations of mean arterial pressure and following spinal cord injury. Conclusion: This pilot study indicates that extradural NIRS monitoring of the spinal cord is feasible as a non-invasive optical method to identify changes in spinal cord hemodynamics and oxygenation in real time. Further development of this technique would allow clinicians to monitor real-time physiologic changes within the injured spinal cord during the acute post-injury period.

Through experiments that simulated sideways falls with a mechanical hip impact simulator, we demonstrated the protective effect of hip abductor muscle forces in reducing peak stresses at the femoral neck and the corresponding risk for hip fracture. Over 90 % of hip fractures are due to falls, and an improved understanding the factors that separate injurious and non-injurious falls (via their influence on the peak stress generated at the femoral neck) may lead to improved risk assessment and prevention strategies. The purpose of this study was to measure the effect of muscle forces spanning the hip, and knee boundary conditions, on peak forces and estimated stresses at the femoral neck during simulated falls with a mechanical system. We simulated hip abductor muscle forces and knee boundary conditions with a mechanical hip impact simulator and measured forces and stresses at the femoral neck during sideways falls. Peak compressive and tensile stresses, shear force, bending moment, and axial force are each associated with hip abductor muscle forces and knee boundary conditions (p

Current neck injury criteria do not include limits for lateral bending combined with axial compression and this has been observed as a clinically relevant mechanism, particularly for rollover motor vehicle crashes. The primary objectives of this study were to evaluate the effects of lateral eccentricity (the perpendicular distance from the axial force to the centre of the spine) on peak loads, kinematics, and spinal canal occlusions of subaxial cervical spine specimens tested in dynamic axial compression (0.5 m/s). Twelve 3-vertebra human cadaver cervical spine specimens were tested in two groups: low and high eccentricity with initial eccentricities of 1 and 150% of the lateral diameter of the vertebral body. Six-axis loads inferior to the specimen, kinematics of the superior-most vertebra, and spinal canal occlusions were measured. High speed video was collected and acoustic emission (AE) sensors were used to define the time of injury. The effects of eccentricity on peak loads, kinematics, and canal occlusions were evaluated using unpaired Student t-tests. The high eccentricity group had lower peak axial forces (1544 ± 629 vs. 4296 ± 1693 N), inferior displacements (0.2 ± 1.0 vs. 6.6 ± 2.0 mm), and canal occlusions (27 ± 5 vs. 53 ± 15%) and higher peak ipsilateral bending moments (53 ± 17 vs. 3 ± 18 Nm), ipsilateral bending rotations (22 ± 3 vs. 1 ± 2°), and ipsilateral displacements (4.5 ± 1.4 vs. -1.0 ± 1.3 mm, p0.05 for all comparisons). These results provide new insights to develop prevention, recognition, and treatment strategies for compressive cervical spine injuries with lateral eccentricities.

CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a recently described animal model of traumatic brain injury (TBI) that primarily produces diffuse axonal injury (DAI) characterized by white matter inflammation and axonal damage. CHIMERA was specifically designed to reliably generate a variety of TBI severities using precise and quantifiable biomechanical inputs in a nonsurgical user-friendly platform. The objective of this study was to define the lower limit of single impact mild TBI (mTBI) using CHIMERA by characterizing the dose-response relationship between biomechanical input and neurological, behavioral, neuropathological and biochemical outcomes. Wild-type male mice were subjected to a single CHIMERA TBI using six impact energies ranging from 0.1 to 0.7 J, and post-TBI outcomes were assessed over an acute period of 14 days. Here we report that single TBI using CHIMERA induces injury dose- and time-dependent changes in behavioral and neurological deficits, axonal damage, white matter tract microgliosis and astrogliosis. Impact energies of 0.4 J or below produced no significant phenotype (subthreshold), 0.5 J led to significant changes for one or more phenotypes (threshold), and 0.6 and 0.7 J resulted in significant changes in all outcomes assessed (mTBI). We further show that linear head kinematics are the most robust predictors of duration of unconsciousness, severity of neurological deficits, white matter injury, and microgliosis following single TBI. Our data extend the validation of CHIMERA as a biofidelic animal model of DAI and establish working parameters to guide future investigations of the mechanisms underlying axonal pathology and inflammation induced by mechanical trauma.

Spinal cord injury (SCI) researchers have predominately utilized rodents and mice for in vivo SCI modeling and experimentation. From these small animal models have come many insights into the biology of SCI, and a growing number of novel treatments that promote behavioral recovery. It has, however, been difficult to demonstrate the efficacy of such treatments in human clinical trials. A large animal SCI model that is an intermediary between rodent and human SCI may be a valuable translational research resource for pre-clinically evaluating novel therapies, prior to embarking upon lengthy and expensive clinical trials. Here, we describe the development of such a large animal model. A thoracic spinal cord injury at T10/11 was induced in Yucatan miniature pigs (20-25 kg) using a weight drop device. Varying degrees of injury severity were induced by altering the height of the weight drop (5, 10, 20, 30, 40, and 50 cm). Behavioral recovery over 12 weeks was measured using a newly developed Porcine Thoracic Injury Behavior Scale (PTIBS). This scale distinguished locomotor recovery among animals of different injury severities, with strong intra-observer and inter-observer reliability. Histological analysis of the spinal cords 12 weeks post-injury revealed that animals with the more biomechanically severe injuries had less spared white matter and gray matter and less neurofilament immunoreactivity. Additionally, the PTIBS scores correlated strongly with the extent of tissue sparing through the epicenter of injury. This large animal model of SCI may represent a useful intermediary in the testing of novel pharmacological treatments and cell transplantation strategies.

Sideways falls are largely responsible for the highly prevalent osteoporotic hip fractures in today's society. These injuries are dynamic events, therefore dynamic FE models validated with dynamic ex vivo experiments provide a more realistic simulation than simple quasi-static analysis. Drop tower experiments using cadaveric specimens were used to identify the material mapping strategy that provided the most realistic mechanical response under impact loading. The present study tested the addition of compression-tension asymmetry, tensile bone damage, and cortical-specific strain rate dependency to the material mapping strategy of fifteen dynamic FE models of the proximal femur, and found improved correlations and reduced error for whole bone stiffness (R2 = 0.54, RSME = 0.87kN/mm) and absolute maximum force (R2 = 0.56, RSME =0.57kN), and a high correlation in impulse response (R2 = 0.82, RSME =12.38kg/s). Simulations using fully bonded nodes between the rigid bottom plate and PMMA cap supporting the femoral head had higher correlations and less error than simulations using a frictionless sliding at this contact surface. Strain rates over 100/s were observed in certain elements in the femoral neck and trochanter, indicating that additional research is required to better quantify the strain rate dependencies of both trabecular and cortical bone at these strain rates. These results represent the current benchmark in dynamic FE modeling of the proximal femur in sideways falls. Future work should also investigate improvements in experimental validation techniques by developing better displacement measurements and by enhancing the biofidelity of the impact loading wherever possible.

Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

STUDY DESIGN: Quantitative in vivo ultrasound imaging study of spinal cord and dura morphology after acute experimental spinal cord injury (SCI) and decompression in a pig model. OBJECTIVE: To study the morphological changes of the spinal cord and dura immediately after surgical decompression for acute SCI. SUMMARY OF BACKGROUND DATA: Surgical decompression for traumatic SCI is currently a topic of debate. After decompression, relief of bony impingement on the thecal sac and spinal cord can be confirmed intraoperatively. However, postoperative imaging often reveals that the cord has swollen to fill the subarachnoid space. Little is known about the extent and timing of this morphological response. METHODS: Yucatan miniature pigs received sham surgery (N = 1) or a moderate (N = 6, 20 g, 2.3 m/s) or high (N = 6, 20 g, 4.7 m/s) severity weight-drop SCI followed by 8 hours of sustained compression (100 g) and 6 hours of postdecompression monitoring. Sagittal-plane ultrasound images were used to quantify spinal cord, dura, and subarachnoid space dimensions preinjury and once per hour after decompression. RESULTS: Animals with a moderate SCI exhibited a residual cord deformation of up to 0.64 mm within 10 minutes of decompression, which tended to resolve during 6 hours because of tissue relaxation and swelling. For animals with high-severity SCIs, cord swelling was immediate and resulted in occlusion of the subarachnoid space within 10 minutes to 5 hours, whereas this occurred for only half of the moderate injury group. CONCLUSION: Decompression of an acute SCI may result in residual cord deformation followed by gradual swelling or immediate swelling leading to subarachnoid occlusion. The response is dependent on initial injury severity. These observations may partly explain the lack of benefit of decompression in some patients and suggest a need to reduce cord swelling to optimize the clinical outcome after acute SCI.

Acoustic emission (AE) sensors are a reliable tool in detecting fracture, however they have not been used to differentiate between compressive osseous and tensile ligamentous failures in the spine. This study evaluated the effectiveness of AE data in detecting the time of injury of ligamentum flavum (LF) and vertebral body (VB) specimens tested in tension and compression, respectively, and in differentiating between these failures. AE signals were collected while LF (n=7) and VB (n=7) specimens from human cadavers were tested in tension and compression (0.4 m/s), respectively. Times of injury (time of peak AE amplitude) were compared to those using traditional methods (VB: time of peak force, LF: visual evidence in high speed video). Peak AE signal amplitudes and frequencies (using Fourier and wavelet transformations) for the LF and VB specimens were compared. In each group, six specimens failed (VB, fracture; LF, periosteal stripping or attenuation) and one did not. Time of injury using AE signals for VB and LF specimens produced average absolute differences to traditional methods of 0.7 (SD 0.2) ms and 2.4 (SD 1.5) ms (representing 14% and 20% of the average loading time), respectively. AE signals from VB fractures had higher amplitudes and frequencies than those from LF failures (average peak amplitude 87.7 (SD 6.9) dB vs. 71.8 (SD 9.8) dB for the inferior sensor, p

Vertebral compression fracture repair aims to relieve pain and improve function by restoring vertebral structure and biomechanics, but is still associated with risks arising from polymethylmethacrylate cement extravasation. The Kiva® Vertebral Compression Fracture Treatment System, a stacked coil implant made of polyetheretherketone and delivered over a guide-wire, is a novel device designed to provide height restoration and mechanical stabilization, while improving cement containment and minimizing disruption of cancellous bone. The objective of this study was to determine whether the Kiva system is as effective as balloon kyphoplasty at restoring mechanical properties in osteoporotic vertebral compression fractures.Wedge fractures were created in the middle vertebra of fourteen osteoporotic three-vertebra spine segments and then repaired with either the Kiva or kyphoplasty procedure. Height, stiffness and displacement under compression of the spine segments were measured for four conditions: intact, fractured, augmented, and post-cyclic eccentric loading (50,000cycles, 200-500N, 30mm anterior lever arm).No significant differences were seen between the two procedures for height restoration, stiffness at high or low loads, or displacement under compression. However, the Kiva System required an average of 66% less cement than kyphoplasty to achieve these outcomes (mean 2.6 (SD 0.4) mL v. mean 7.5 (SD 0.8) mL 0; P0.01). Extravasations and excessive posterior cement flow were also significantly lower with Kiva (0/7 v. 4/7; P.05).Kiva exhibits similar biomechanical performance to balloon kyphoplasty, but may reduce the risk of extravasation through the containment mechanism of the implant design and by reducing cement volume.

Adjacent level degeneration that occurs above and/or below long fusion constructs is a documented clinical problem that is widely believed to be associated with the considerable change in stiffness caused by the fusion. Some researchers have suggested that early degeneration at spinal joints adjacent to a fusion could be treated by implanting total disc replacements at these levels. It is thought that further degeneration could be prevented through the disc replacement's design aims to reproduce normal disc heights, kinematics and tissue loading. For this reason, there is a clinical need to evaluate if a total disc replacement can maintain both the quantity of motion (i.e. range) and the quality of motion (i.e. center of rotation and coupling) at segments adjacent to a long spinal fusion. The purpose of this study was to experimentally evaluate range of motion (ROM-the intervertebral motion measured) and helical axis of motion (HAM) changes due to one- and two-level Maverick total disc replacement (TDR) adjacent to a long spinal fusion.Seven spine specimens (T8-S1) were used in this study (66 ± 19 years old, 3F/4 M). A continuous pure moment of ±5.0 Nm was applied to the specimen in flexion-extension (FE), lateral bending (LB) and axial rotation (AR), with a compressive follower preload of 400 N. The 5.0 Nm data were analyzed to evaluate the operated segment biomechanics at the level of the disc replacements. The data were also analyzed at lower moments using a modified version of Panjabi's proposed "hybrid" method to evaluate adjacent segment kinematics (intervertebral motion at the segments adjacent to the fusion) under identical overall (T8-S1) specimen rotations. The motion of each vertebra was monitored with an optoelectronic camera system. The biomechanical test was completed for (1) the intact condition and repeated after each surgical technique was applied to the specimen, (2) capsulotomy at L4-L5 and L5-S1, (3) T8-L4 fusion and capsulotomy at L4-L5 and L5-S1, (4) Maverick at L4-L5, and (5) Maverick at L5-S1. The capsulotomy was performed to allow measurement of facet joint loads in a companion study. Paired t tests were used to determine if differences in the kinematic parameters measured were significant. Holm-Sidak corrections for multiple comparisons were applied where appropriate.Under the 5.0 Nm loads, L4-L5 ROMs tended to decrease in all directions following L4-L5 Maverick replacement (mean = 22 %, compared to the fused condition). Two-level Maverick implantation also tended to reduce L4-S1 ROM (mean 18, 7 and 31 % in FE, LB and AR, respectively, compared to the fused condition without TDR). Following TDR replacement, the HAM location tended to shift posteriorly in FE (at L5-S1), anteriorly in AR, and inferiorly in LB. However, although the above-mentioned trends were observed, neither one- nor two-level TDR replacement showed statistically significant ROM or HAM change in any of the three directions. At the identical T8-S1 posture identified by the modified hybrid analysis, the L4-L5 and L5-S1 levels underwent significant larger motions, relative to the overall specimen rotation, after fusion. In the hybrid analysis, there were no significant differences between the ROM after fusion with intact natural discs at L4-L5 and L5-S1 and the motions at those levels with one or two TDRs implanted.The present results demonstrated that one or two Maverick discs implanted subjacent to a long thoracolumbar fusion preserved considerable and intact-like ranges of motion and maintained motion patterns similar to the intact specimen, in this ex vivo study with applied pure moments and compressive follower preload. The hybrid analysis demonstrated that, after fusion, the TDR-implanted levels are required to undergo large rotations, relative to those necessary before fusion, in order to achieve the same motion between T8 and S1. Additional clinical and biomechanical research is necessary to determine if such a kinematic demand would be made on these levels clinically and the biomechanical performance of these implants if it were.

Vertebral body fractures are the most common type of osteoporotic fractures.1,2 These fractures represent a growing public health concern because the incidence is projected to increase as the population ages.3 Vertebral fractures are associated with substantial increases in back pain, functional limitation, disability, and mortality.4,5 Falls are a major contributing factor to the occurrence of osteoporotic fractures6; 41% of vertebral fractures in older men are associated with falls from standing height or lower.7 The most common vertebral fracture site for older men is the lumbosacral spine, which represents 56% of all cases.7 Falls from standing height or lower also account for between 8% and 26% of spinal cord injuries,7,8 and more than two-thirds of these injuries occur in older adults.8 The risk of vertebral fracture in a backward fall depends, by definition, on a “factor of safety.” This factor of safety is defined as the ratio of the force that will typically result in failure under a loading configuration similar to that applied in the fall (i.e., tolerance) divided by the peak-applied force. Previous studies have measured the force applied to the buttocks in subinjurious backward falls in human subjects.9 The compressive force required to cause fracture of lumbar vertebrae has been determined by testing isolated cadaver spine segments.10–17 However, the peak forces occurring at the lumbosacral spine during a backward fall are not known, and this is a barrier to the development of injury prevention strategies. An intervention that has been suggested to reduce the incidence of fall-related fractures is the use of compliant or low-stiffness flooring.9,18,19 In a previous experimental study conducted by a subset of this study’s authors, human subjects fell from standing onto floors of various stiffnesses.9 Impact forces at the buttocks decreased with decreases in floor stiffness; however, the effect on spine forces was not addressed. To determine the effect of floor stiffness on spine forces experimentally, direct measurement of spinal component loads would be necessary; however, these are difficult to measure even during benign activities in vivo.10,11 Numerical models have been used to study the loads generated in the human spine during various activities,12–15 and this method has also been used to study spinal forces during trauma.16–18 Some of the previous models have been complex, have simulated multiple degrees of freedom at each joint, and have incorporated anatomic details such as the rib cage, lumbar muscles, viscera, facet joints, and intervertebral discs.12,14–16 Axial spine forces are related to fracture risk19–23; therefore, they are of primary interest in this study. It was our objective to develop an appropriate model to allow examination of the effect of floor stiffness on axial loading at various levels of the spine during a fall. We had access to a unique set of data to incorporate into our model. These human subject-specific data from our previous experimental study provided a level of verification for the present computational model.9 No previous mathematical modelling or experimental studies have examined spine forces resulting from a backward fall onto the buttocks. Accordingly, the specific objectives in this study were (1) to develop and verify a lumped-parameter model to predict intervertebral forces at several levels of the lumbosacral spine during backward falls from standing, (2) to evaluate the effect of floor stiffness on these forces, and (3) to examine how these compare with the axial force associated with fracture of the spine.

The relationship between bony spinal column and spinal cord injury during an injury event is not well understood. While several studies have measured spinal canal occlusion during axial impact, there has been limited work done to quantify the spinal cord compression or deformation during simulated injury. Because the cord is a viscoelastic solid it may provide resistance to bone fragments, ligaments or other elements that move into the canal and impinge it during column injury. This would differentiate the measurement of cord compression from the measurement of occlusion of an empty canal. In the present study, a novel method of visualizing and quantifying spinal cord deformation during dynamic head-first impact of ex vivo human cervical spine specimens (N=6) was developed. A radiodense, biofidelic surrogate spinal cord was imaged in the spinal canal using high speed cineradiography at 1000 frames per second. The dorsal-ventral diameter of the cord was measured at 1.5mm increments along its length for each frame of the radiographic footage. The resulting cord deformations were used to determine the theoretical neurological outcome of the impact based on published in vivo ferret studies. The corresponding probability of recovery for the spinal cord deformations in these tests ranged between 8% for atlantoaxial dislocation injury and 95% for mid-cervical spine hyperextension injury (based on the ferret data). Clinically relevant spinal column fracture patterns were produced in this study. Language: en

To evaluate a prototype sagittal plane surrogate neck model designed to provide a biofidelic response to head-first impacts with a straightened cervical posture.Published biomechanical studies were used in the design to define the range of motion (ROM) and stiffness in both flexion-extension rotation and axial compression. The neck was tested in a series of head-first impacts on a drop tower to investigate the temporal aspects of the kinetic axial force response for the head and neck. A separate series of flexion-extension tests was conducted in a spinal motion simulator to assess its ROM and bending stiffness.In impacts with a 104 N axial preload, the surrogate head and neck displayed a bimodal response to force development in agreement with published studies of cadaveric head-first impacts. In bending without an axial preload, the neck had an ROM and bending stiffness representative of cadaveric human spines and it included a large neutral zone, but with the incremental addition of axial preload these metrics were somewhat reduced.The model appears suitable for studying the scenario of sagittal plane, aligned column impacts. Further design refinements are required to provide biofidelity in both sagittal bending and head-first impacts using a single level of axial preload. This would be necessary to study impact scenarios where considerable sagittal plane neck rotation occurs at impact. The model has identified some key concepts that must be considered for continued design and improvement of a dedicated dummy neck for head-first impacts.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To determine the effect of age and sex on the three-dimensional kinematics of the cervical spine. SUMMARY OF BACKGROUND DATA: Spine kinematics information has important implications for biomechanical model development, anthropomorphic test device development, injury prevention, surgical treatment, and safety equipment design. There is a paucity of data of this type available for children, and it is unknown whether cervical spine kinematics of the pediatric population is different than that of adults. The helical axis of motion (HAM) of the spine provides unique information about the quantity and quality (coupling etc.) of the measured motion. METHODS: Ninety subjects were recruited and divided into 6 groups based on sex and age (young children aged 4-10 years, older children aged 11-17 years, adults aged 25+ years). Subjects actively moved their head in axial rotation, lateral bending, and flexion/extension. An optoelectronic motion analysis system recorded the position of infrared markers placed on the first thoracic vertebrae (T1) and on tight-fitting headgear worn by the subjects. HAM parameters were calculated for the head motion with respect to T1. RESULTS: HAM location in axial rotation and flexion/extension was more anterior in young females compared to adult females. Young females had a more anterior HAM location in flexion/extension compared to young males, indicating an effect of sex. For females, the HAM locations of adults were superior to those of children in flexion/extension and lateral bending whereas in males the HAM locations of adults were inferior to those of children. Age-related differences in HAM orientation were also observed in axial rotation and lateral bending. CONCLUSION.: Cervical spine kinematics vary with age and sex. The variation in spine mechanics based on age and sex found in the present study may indicate general trends that would grow stronger in even younger children (age Language: en

To prevent spinal cord injury, optimize treatments for it, and better understand spinal cord pathologies such as spondylotic myelopathy, the interaction between the spinal column and the spinal cord during injury and pathology must be understood. The spinal cord is a complex and very soft tissue that changes properties rapidly after death and is difficult to model. Our objective was to develop a physical surrogate spinal cord with material properties closely corresponding to the in vivo human spinal cord that would be suitable for studying spinal cord injury under a variety of injurious conditions. Appropriate target material properties were identified from published studies and several candidate surrogate materials were screened, under uniaxial tension, in a materials testing machine. QM Skin 30, a silicone elastomer, was identified as the most appropriate material. Spinal cords manufactured from QM Skin 30 were tested under uniaxial tension and transverse compression. Rectangular specimens of QM Skin 30 were also tested under uniform compression. QM Skin 30 produced surrogate cords with a Young's modulus in tension and compression approximately matching values reported for in vivo animal spinal cords (0.25 and 0.20 MPa, respectively). The tensile and compressive Young's modulus and the behavior of the surrogate cord simulated the nonlinear behavior of the in vivo spinal cord.

Study design An ex vivo biomechanical study using porcine spinal segments. Objective To produce a biomechanical model of both spondylolysis and spondylolisthesis using an accelerated cyclic loading model with intermittent impulse loads. Summary of background data Only a few models of spondylolisthesis appropriate for biomechanical testing have been presented previously. Past modeling attempts have largely required nonphysiologic gross fracture of the pars before testing and have resulted in nonphysiologic endplate fracture. In these tests no clinically relevant spondylolisthesis was seen at the end of testing. A reproducible, clinically relevant model of both spondylolysis and spondylolisthesis would allow study of these disease processes, and facilitate the development and evaluation of advanced spinal implants optimized specifically for these pathologies. Methods Five porcine lumbar functional spinal units were tested (2 L4-L5, 3 L6-S1) after small notches had been created in the pars and after the disc had specific collagen fibers in the anterior anulus sectioned. Specimens were loaded with a constant cranial-caudal compressive force of 300 N and the application of cyclic anterior shear loads between 300 and 600 N with intermittent impulse loads to 1500 N until pars fracture occurred. Elevated cyclic loading then continued between 500 and 800 N. Results All specimens displayed bilateral pars fracture with the fractures passing through the points of notching and no damage to endplates or facet joints. Clinically-relevant Grade II spondylolisthesis was achieved in all 5 specimens. The mean slip at the conclusion of testing was 33%. Conclusion Cyclic shear loading with intermittent impulse loads can reliably create fracture in the pars interarticularis in ex vivo porcine spine segments. Subsequent cyclic anterior motion of the superior vertebra results in clinically-relevant spondylolysis and spondylolisthesis.

Thoracolumbar burst fracture is one of the most common and most studied injuries of the spine. Radiography and quantitative discomanometry have previously demonstrated that intervertebral discs adjacent to a burst fracture were disrupted; however, there have been conflicting data on the properties of the next-adjacent discs. Also, no data exists on the localization of injury within each disc. The objective of this study is to use an in vitro biomechanical design to examine the flexibility differences of intervertebral discs adjacent and next-adjacent to burst fracture vertebrae. Ten cadaveric thoracolumbar (T11–L3) spines with L1 burst fracture included adjacent (T12–L1, L1–L2) and next-adjacent (T11–T12, L2–L3) intervertebral discs. The bending flexibilities (μm/N) of each disc under 50 N of compression were determined at 25 points: the center point, along with the combinations of three radii (1 cm, 2 cm, 3 cm) and eight angles. The overall flexibility of each disc and the presence of any regional differences were then evaluated. Across all radii, the T11μT12 disc was statistically less flexible than the other three discs (p < 0.01). The difference between the flexibilities of the average anterior region and the average posterior region was significant at many 2-cm and all 3-cm radii; this difference was greater in the T12–L1 disc than in any of the other three discs. Thus, the upper next-adjacent intervertebral disc (T11–T12) was not as susceptible to mechanical disruption as were the other three discs. The anterior region of each disc may also have a higher propensity for mechanical disruption than the posterior region, especially at larger radii.

STUDY DESIGN Nucleus pressure was measured within porcine intervertebral discs (IVDs) with a novel in-fiber Bragg grating (FBG) sensor (0.4 mm diameter) and a strain gauge (SG) sensor (2.45 mm). OBJECTIVE To validate the accuracy of a new FBG pressure sensor designed for minimally invasive measurements of nucleus pressure. SUMMARY OF BACKGROUND DATA Although its clinical utility is controversial, it is possible that the predictive accuracy of discography can be improved with IVD pressure measurements. These measurements are typically obtained using needle-mounted SG sensors inserted into the nucleus. However, by virtue of their size, SG sensors alter disc mechanics, injure anulus fibers, and can potentially initiate or accelerate degenerative changes thereby limiting their utility particularly clinically. METHODS Six functional spinal units were loaded in compression from 0 N to 500 N and back to 0 N; nucleus pressure was measured using the FBG and SG sensors at various locations along anterior and anterolateral axes. RESULTS On average maximum IVD pressures measured using the FBG and SG sensors were within 9.39% of each other. However, differences between maximum measured pressures from the FBG and SG sensors were larger (22.2%) when the SG sensor interfered with vertebral endplates (P < 0.05). The insertion of the FBG sensor did not result in visible damage to the anulus, whereas insertion of the SG sensor resulted in large perforations in the anulus through which nucleus material was visible. CONCLUSION The new FBG sensor is smaller and less invasive than any previously reported disc pressure sensor and gave results consistent with previous disc pressure studies and the SG sensor. There is significant potential to use this sensor during discography while avoiding the controversy associated with disc injury as a result of sensor insertion.

Background Proximal humerus fractures are a common fragility fracture that significantly affects the independence of older adults. The outcomes of these fractures are frequently disappointing and previous systematic reviews are unable to guide clinical practice. Through an integrated knowledge user collaboration, we sought to map the breadth of literature available to guide the management of proximal humerus fractures. Methods We utilized a scoping review technique because of its novel ability to map research activity and identify knowledge gaps in fields with diverse treatments. Through multiple electronic database searches, we identified a comprehensive body of proximal humerus fracture literature that was classified into eight research themes. Meta-data from each study were abstracted and descriptive statistics were used to summarize the results. Results 1,051 studies met our inclusion criteria with the majority of research being performed in Europe (64%). The included literature consists primarily of surgical treatment studies (67%) and biomechanical fracture models (10%). Nearly half of all clinical studies are uncontrolled case series of a single treatment (48%). Non-randomized comparative studies represented 12% of the literature and only 3% of the studies were randomized controlled trials. Finally, studies with a primary outcome examining the effectiveness of non-operative treatment or using a prognostic study design were also uncommon (4% and 6%, respectively). Conclusions The current study provides a comprehensive summary of the existing proximal humerus fracture literature using a thematic framework developed by a multi-disciplinary collaboration. Several knowledge gaps have been identified and have generated a roadmap for future research priorities. Electronic supplementary material The online version of this article (doi:10.1186/s12891-015-0564-8) contains supplementary material, which is available to authorized users.

Visualization and analysis of the rodent spinal cord subject to experimental spinal cord injury (SCI) has almost completely been limited to naked-eye observations, and a single measure of gross spinal cord motion due to injury. This study introduces a novel method which utilizes MRI to quantify the deformation of the rodent spinal cord due to imposed, clinically-relevant injuries - specifically, cervical contusion and dislocation mechanisms. The image registration methods were developed using the Advanced Normalization Tools package, which incorporate rigid, affine and deformable registration steps. The proposed method is validated against a fiducial-based, 'gold-standard' measure of spinal cord tissue motion. The validation analysis yielded accuracy (and precision) values of 62 μm (49 μm), 73 μm (79 μm) and 112 μm (110 μm), for the medio-lateral, dorso-ventral and cranio-caudal directions, respectively. The internal morphological change of the spinal cord has never before been quantified, experimentally. This study demonstrates the capability of this method and its potential for future application to in vivo rodent models of SCI.

Contributing to slow advance of finite element (FE) simulations for hip fracture risk prediction, into clinical practice, could be a lack of consensus in the biomechanics community on how to map properties to the models. Thus, the aim of the present study was first, to systematically quantify the influence of the modulus-density relationship (E-ρ) and the material mapping method (MMM) on the predicted mechanical response of the proximal femur in a side-ways fall (SWF) loading configuration and second, to perform a model-to-model comparison of the predicted mechanical response within the femoral neck for all the specimens tested in the present study, using three different modelling techniques that have yielded good validation outcome in terms of surface strain prediction and whole bone response according to the literature. We found the outcome to be highly dependent on both the E-ρ relationship and the MMM. In addition, we found that the three modelling techniques that have resulted in good validation outcome in the literature yielded different principal strain prediction both on the surface as well as internally in the femoral neck region of the specimens modelled in the present study. We conclude that there exists a need to carry out a more comprehensive validation study for the SWF loading mode to identify which combination of MMMs and E-ρ relationship leads to the best match for whole bone and local mechanical response. The MMMs tested in the present study have been made publicly available at https://simtk.org/home/mitk-gem.

Whole-body vibration has been identified as a potential stressor to spinal cord injury (SCI) patients during pre-hospital transportation. However, the effect that such vibration has on the acutely injured spinal cord is largely unknown, particularly in the frequency domain of 5 Hz in which resonance of the spine occurs. The objective of the study was to investigate the consequences of resonance vibration on the injured spinal cord. Using our previously characterized porcine model of SCI, we subjected animals to resonance vibration (5.7±0.46 Hz) or no vibration for a period of 1.5 or 3.0 h. Locomotor function was assessed weekly and cerebrospinal fluid (CSF) samples were collected to assess different inflammatory and injury severity markers. Spinal cords were evaluated histologically to quantify preserved white and gray matter. No significant differences were found between groups for CSF levels of monocyte chemotactic protein-1, interleukin 6 (IL-6) and lL-8. Glial fibrillary acidic protein levels were lower in the resonance vibration group, compared with the non-vibrated control group. Spared white matter tissue was increased within the vibrated group at 7 d post-injury but this difference was not apparent at the 12-week time-point. No significant difference was observed in locomotor recovery following resonance vibration of the spine. Here, we demonstrate that exposure to resonance vibration for 1.5 or 3 h following SCI in our porcine model is not detrimental to the functional or histological outcomes. Our observation that a 3.0-h period of vibration at resonance frequency induces modest histological improvement at one week post-injury warrants further study.

Experimental data suggest that lumbar torsion contributes to lumbar disc degenerative changes, such as instability, spondylolisthesis and spinal canal stenosis. However, some basic mechanical characteristics of the lumbar spine under torsional loading have not yet been reported in detail. For example, the function of the facet joints under combined mechanical loads such as torsion with superimposed flexion or extension postures is an area of interest about which little biomechanical data have been reported. In this study, the kinematic response to axial torsion with superimposed axial compression (200 N), compression-flexion (3 and 6 Nm) and compression-extension (3 and 6 Nm) was investigated in 10 cadaveric lumbar functional spinal units. Range of motion (ROM), and helical axes of motion (HAM), were analyzed. There was no difference in ROM between no preload, pure compressive and flexion-compression preload conditions. The ROM was significantly reduced by both extension-compression preload conditions (11% reduction for 3 Nm and 19% reduction for 6 Nm of extension) compared to the pure compressive preload. For no preload, the average HAM position in the transverse plane of the intervertebral disc was near the posteriormost part of the disc and located laterally on the side contralateral to the applied torsional moment. In the transverse plane, the HAM position showed a discrete trend towards the posterior part of the specimens during extension. Kinematic data were visualized using computer animation techniques and CT-based reconstructions of the respective specimens. This information may be used for identifying and characterizing physiologic and pathologic motion and for specifying conservative and surgical treatment concepts and, thus, may find application to identifying indications for spinal fusion or in evaluating the effect of future semi-flexible instrumentation.