Incremental increases in physiological fluid shear progressively alter pathogenic phenotypes and gene expression in multidrug resistant Salmonella.

The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant S. Typhimurium (ST313 D23580) under different fluid shear conditions relevant to its transition from the intestinal tract to the bloodstream. We report that D23580 exhibited incremental changes in transcriptomic profiles that correlated with its pathogenic phenotypes in response to these progressive increases in fluid shear. This is the first demonstration that incremental changes in fluid shear forces alter stress responses and gene expression in any ST313 strain and offers mechanistic insight into how forces encountered by bacteria during infection might impact their disease-causing ability in unexpected ways.

Biomechanical Considerations of Refreshable Braille and Tactile Graphics Toward Equitable Access: A Review.

This review highlights the biomechanical foundations of braille and tactile graphic discrimination within the context of design innovations in information access for the blind and low-vision community. Braille discrimination is a complex and poorly understood process that necessitates the coordination of motor control, mechanotransduction, and cognitive-linguistic processing. Despite substantial technological advances and multiple design attempts over the last fifty years, a low-cost, high-fidelity refreshable braille and tactile graphics display has yet to be delivered. Consequently, the blind and low-vision communities are left with limited options for information access. This is amplified by the rapid adoption of graphical user interfaces for human-computer interaction, a move that the blind and low vision community were effectively excluded from. Text-to-speech screen readers lack the ability to convey the nuances necessary for science, technology, engineering, arts, and math education and offer limited privacy for the user. Printed braille and tactile graphics are effective modalities but are time and resource-intensive, difficult to access, and lack real-time rendering. Single- and multiline refreshable braille devices either lack functionality or are extremely cost-prohibitive. Early computational models of mechanotransduction through complex digital skin tissue and the kinematics of the braille reading finger are explored as insight into device design specifications. A use-centered, convergence approach for future designs is discussed in which the design space is defined by both the end-user requirements and the available technology.

Intervertebral Disc Elastography to Relate Shear Modulus and Relaxometry in Compression and Bending.

Intervertebral disc degeneration is the most recognized cause of low back pain, characterized by the decline of tissue structure and mechanics. Image-based mechanical parameters (e.g., strain, stiffness) may provide an ideal assessment of disc function that is lost with degeneration but unfortunately remains underdeveloped. Moreover, it is unknown whether strain or stiffness of the disc may be predicted by MRI relaxometry (e.g. T1 or T2), an increasingly accepted quantitative measure of disc structure. In this study, we quantified T1 and T2 relaxation times and in-plane strains using displacement-encoded MRI within the disc under physiological levels of compression and bending. We then estimated shear modulus in orthogonal image planes and compared these values to relaxation times and strains within regions of the disc. Intratissue strain depended on the loading mode, and shear modulus in the nucleus pulposus was typically an order of magnitude lower than the annulus fibrosis, except in bending, where the apparent stiffness depended on the loading. Relative shear moduli estimated from strain data derived under compression generally did not correspond with those from bending experiments, with no correlations in the sagittal plane and only 4 of 15 regions correlated in the coronal plane, suggesting that future inverse models should incorporate multiple loading conditions. Strain imaging and strain-based estimation of material properties may serve as imaging biomarkers to distinguish healthy and diseased discs. Additionally, image-based elastography and relaxometry may be viewed as complementary measures of disc structure and function to assess degeneration in longitudinal studies.

Novel Osteochondral Biotemplate Improves Long-term Cartilage Repair Compared With Microfracture in an Ovine Model.

BACKGROUND: Current cartilage repair therapies do not re-create the complex mechanical interface between cartilage and bone, which is critical for long-term repair durability. New biomaterial designs that include hard tissue-soft tissue interface structures offer promise to improve clinical outcomes. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the efficacy and safety of a naturally derived osteochondral biotemplate with a novel contiguous hard tissue-soft tissue interface in an ovine model as a regenerative solution for articular cartilage defects. It was hypothesized that the osteochondral biotemplate would produce structurally superior repair tissue compared with microfracture over a 13-month period. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral biotemplates were manufactured from porcine cancellous bone. Skeletally mature sheep (N = 30) were randomly allocated to 3 groups: early healing stage (euthanasia at 4 months), 6-month treatment, and 13-month treatment. In the early healing stage group, an 8 mm-diameter by 5 mm-deep osteochondral defect was created on the medial femoral condyle and treated at the time of iatrogenic injury with an osteochondral biotemplate. The contralateral limb received the same treatment 2 months later. In the 6- and 13-month treatment groups, 1 limb received the same osteochondral procedure as the early healing stage group. In the contralateral limb, an 8 mm-diameter, full-thickness cartilage defect (1-2 mm deep) was created and treated with microfracture. Cartilage repair and integration were quantitatively and qualitatively assessed with gross inspection, histological evaluation, and magnetic resonance imaging (MRI). Wilcoxon signed-rank and McNemar tests were used to compare the treatments. RESULTS: At 6 and 13 months after treatment, the biotemplate was not present histologically. At 13 months, the biotemplate treatment demonstrated statistically higher histological scores than microfracture for integration with surrounding cartilage (biotemplate: 74 ± 31; microfracture: 28 ± 39; P = .03), type 2 collagen (biotemplate: 72 ± 33; microfracture: 40 ± 38; P = .02), total cartilage (biotemplate: 71 ± 9; microfracture: 59 ± 9; P = .01), and total integration (biotemplate: 85 ± 15; microfracture: 66 ± 20; P = .04). The osteochondral biotemplate treatment produced a notable transient nonneutrophilic inflammatory response that appeared to approach resolution at 13 months. MRI results were not statistically different between the 2 treatments. CONCLUSION: Even with the inflammatory response, after 13 months, the osteochondral biotemplate outperformed microfracture in cartilage regeneration and demonstrated superiority in integration between the repair tissue and host tissue as well as integration between the newly formed cartilage and the underlying bone. CLINICAL RELEVANCE: This work has demonstrated the clinical potential of a novel biomaterial template to regenerate the complex mechanical interface between cartilage and the subchondral bone.

Design Considerations for the Attenuation of Translational and Rotational Accelerations in American Football Helmets.

Participants in American football experience repetitive head impacts that induce negative changes in neurocognitive function over the course of a single season. This study aimed to quantify the transfer function connecting the force input to the measured output acceleration of the helmet system to provide a comparison of the impact attenuation of various modern American football helmets. Impact mitigation varied considerably between helmet models and with location for each helmet model. The current data indicate that helmet mass is a key variable driving force attenuation, however flexible helmet shells, helmet shell cutouts, and more compliant padding can improve energy absorption.

Spaceflight Analogue Culture Enhances the Host-Pathogen Interaction Between Salmonella and a 3-D Biomimetic Intestinal Co-Culture Model.

Physical forces associated with spaceflight and spaceflight analogue culture regulate a wide range of physiological responses by both bacterial and mammalian cells that can impact infection. However, our mechanistic understanding of how these environments regulate host-pathogen interactions in humans is poorly understood. Using a spaceflight analogue low fluid shear culture system, we investigated the effect of Low Shear Modeled Microgravity (LSMMG) culture on the colonization of Salmonella Typhimurium in a 3-D biomimetic model of human colonic epithelium containing macrophages. RNA-seq profiling of stationary phase wild type and Δhfq mutant bacteria alone indicated that LSMMG culture induced global changes in gene expression in both strains and that the RNA binding protein Hfq played a significant role in regulating the transcriptional response of the pathogen to LSMMG culture. However, a core set of genes important for adhesion, invasion, and motility were commonly induced in both strains. LSMMG culture enhanced the colonization (adherence, invasion and intracellular survival) of Salmonella in this advanced model of intestinal epithelium using a mechanism that was independent of Hfq. Although S. Typhimurium Δhfq mutants are normally defective for invasion when grown as conventional shaking cultures, LSMMG conditions unexpectedly enabled high levels of colonization by an isogenic Δhfq mutant. In response to infection with either the wild type or mutant, host cells upregulated transcripts involved in inflammation, tissue remodeling, and wound healing during intracellular survival. Interestingly, infection by the Δhfq mutant led to fewer transcriptional differences between LSMMG- and control-infected host cells relative to infection with the wild type strain. This is the first study to investigate the effect of LSMMG culture on the interaction between S. Typhimurium and a 3-D model of human intestinal tissue. These findings advance our understanding of how physical forces can impact the early stages of human enteric salmonellosis.

An Electromyography-Based Constitutive Law for Force Generation in Skeletal Muscle-Part II: Model Validation on the Ankle Joint Complex.

Part II of this study evaluates the predictive ability of the skeletal muscle force model derived in Part I within the ankle joint complex. The model is founded in dimensional analysis and uses electromyography and the muscle force-length, force-velocity, and force-frequency curves as inputs. Seventeen subjects (eight males, nine females) performed five different exercises geared toward activating the primary muscles crossing the ankle joint. Motion capture, force plate, and electromyography data were collected during these exercises for use in the analysis. A constant, Km, was calculated for each muscle of each subject using four of the five exercises. The fifth exercise was then used to validate the results by treating the moments due to muscle forces as known and all other components in Euler's second law as unknown. While muscle forces cannot be directly validated in vivo, methods can be developed to test these values with reasonable confidence. This study compared moments about the ankle joint due to the calculated muscle forces to the sum of the moments due to all other sources and the kinematic terms in the second Newton-Euler equation of rigid body motion. Average percent errors for each subject ranged from 4.2% to 15.5% with a total average percent error across all subjects of 8.2%, while maximum percent errors for each subject ranged from 33.3% to 78.0% with an overall average maximum of 52.4%. Future work will examine sensitivity analyses to identify any potential simplifications to the model and solution process, as well as validate the model on a more complex joint system to ensure it still performs at a satisfactory level.

A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality.

Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites always mediated the statistical relationship between miRNAs and VR-based motor control ( p S o b e l p e r m ≤ 0.05; total effect > 50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes.

Metabolomic response to collegiate football participation: Pre- and Post-season analysis.

Contact sports participation has been shown to have both beneficial and detrimental effects on health, however little is known about the metabolic sequelae of these effects. We aimed to identify metabolite alterations across a collegiate American football season. Serum was collected from 23 male collegiate football athletes before the athletic season (Pre) and after the last game (Post). Samples underwent nontargeted metabolomic profiling and 1131 metabolites were included for univariate, pathway enrichment, and multivariate analyses. Significant metabolites were assessed against head acceleration events (HAEs). 200 metabolites changed from Pre to Post (P < 0.05 and Q < 0.05); 160 had known identity and mapped to one of 57 pre-defined biological pathways. There was significant enrichment of metabolites belonging to five pathways (P < 0.05): xanthine, fatty acid (acyl choline), medium chain fatty acid, primary bile acid, and glycolysis, gluconeogenesis, and pyruvate metabolism. A set of 12 metabolites was sufficient to discriminate Pre from Post status, and changes in 64 of the 200 metabolites were also associated with HAEs (P < 0.05). In summary, the identified metabolites, and candidate pathways, argue there are metabolic consequences of both physical training and head impacts with football participation. These findings additionally identify a potential set of objective biomarkers of repetitive head injury.

Normalized Brain Tissue-Level Evaluation of Volumetric Changes of Youth Athletes Participating in Collision Sports.

Observations of short-term changes in the neural health of youth athletes participating in collision sports (e.g., football and soccer) have highlighted a need to explore potential structural alterations in brain tissue volumes for these persons. Studies have shown biochemical, vascular, functional connectivity, and white matter diffusivity changes in the brain physiology of these athletes that are strongly correlated with repetitive head acceleration exposure. Here, research is presented that highlights regional anatomical volumetric measures that change longitudinally with accrued subconcussive trauma. A novel pipeline is introduced that provides simplified data analysis on standard-space template to quantify group-level longitudinal volumetric changes within these populations. For both sports, results highlight incremental relative regional volumetric changes in the subcortical cerebrospinal fluid that are strongly correlated with head exposure events greater than a 50-G threshold at the short-term post-season assessment. Moreover, longitudinal regional gray matter volumes are observed to decrease with time, only returning to baseline/pre-participation levels after sufficient (5-6 months) rest from collision-based exposure. These temporal structural volumetric alterations are significantly different from normal aging observed in sex- and age-matched controls participating in non-collision sports. Future work involves modeling repetitive head exposure thresholds with multi-modal image analysis and understanding the underlying physiological reason. A possible pathophysiological pathway is presented, highlighting the probable metabolic regulatory mechanisms. Continual participation in collision-based activities may represent a risk wherein recovery cannot occur. Even when present, the degree of the eventual recovery remains to be explored, but has strong implications for the well-being of collision-sport participants.

An Electromyography-Based Constitutive Law for Force Generation in Skeletal Muscle-Part I: Model Development.

This paper proposes a new method for estimating skeletal muscle forces using a model derived from dimensional analysis. It incorporates electromyography signals and muscle force-length, force-velocity, and force-frequency relationships as inputs. The purpose of this model is to provide more accurate estimates of individualized muscle forces to better predict surrounding musculoskeletal tissue and joint contact loading. The derivation begins with dimensional analysis and a selection of critical parameters that define muscle force generation. The resulting constitutive equation gives way to a unique application of inverse-dynamics, one which avoids the issue of indeterminacy when reaction moments and ligament loading are minimized in a joint. The ankle joint is used as an example for developing the equations that culminate into a system of linear equations. A muscle force model capable of being calibrated and then used to predict joint contact and surrounding tissue loading is critical in advancing biomechanics research areas like injury prevention, performance optimization, and tissue engineering, among others. This model's foundation in dimensional analysis, along with its inclusion of electromyography signals, gives promise that it will be physiologically relevant and suitable for application-based studies. A following paper, Part II, will evaluate this premise in an experimental setting.

Development of brain atlases for early-to-middle adolescent collision-sport athletes.

Human brains develop across the life span and largely vary in morphology. Adolescent collision-sport athletes undergo repetitive head impacts over years of practices and competitions, and therefore may exhibit a neuroanatomical trajectory different from healthy adolescents in general. However, an unbiased brain atlas targeting these individuals does not exist. Although standardized brain atlases facilitate spatial normalization and voxel-wise analysis at the group level, when the underlying neuroanatomy does not represent the study population, greater biases and errors can be introduced during spatial normalization, confounding subsequent voxel-wise analysis and statistical findings. In this work, targeting early-to-middle adolescent (EMA, ages 13-19) collision-sport athletes, we developed population-specific brain atlases that include templates (T1-weighted and diffusion tensor magnetic resonance imaging) and semantic labels (cortical and white matter parcellations). Compared to standardized adult or age-appropriate templates, our templates better characterized the neuroanatomy of the EMA collision-sport athletes, reduced biases introduced during spatial normalization, and exhibited higher sensitivity in diffusion tensor imaging analysis. In summary, these results suggest the population-specific brain atlases are more appropriate towards reproducible and meaningful statistical results, which better clarify mechanisms of traumatic brain injury and monitor brain health for EMA collision-sport athletes.

Brain Perfusion Bridges Virtual-Reality Spatial Behavior to TPH2 Genotype for Head Acceleration Events.

Neuroimaging demonstrates that athletes of collision sports can suffer significant changes to their brain in the absence of concussion, attributable to head acceleration event (HAE) exposure. In a sample of 24 male Division I collegiate football players, we examine the relationships between tryptophan hydroxylase 2 (TPH2), a gene involved in neurovascular function, regional cerebral blood flow (rCBF) measured by arterial spin labeling, and virtual reality (VR) motor performance, both pre-season and across a single football season. For the pre-season, TPH2 T-carriers showed lower rCBF in two left hemisphere foci (fusiform gyrus/thalamus/hippocampus and cerebellum) in association with higher (better performance) VR Reaction Time, a dynamic measure of sensory-motor reactivity and efficiency of visual-spatial processing. For TPH2 CC homozygotes, higher pre-season rCBF in these foci was associated with better performance on VR Reaction Time. A similar relationship was observed across the season, where TPH2 T-carriers showed improved VR Reaction Time associated with decreases in rCBF in the right hippocampus/amygdala, left middle temporal lobe, and left insula/putamen/pallidum. In contrast, TPH2 CC homozygotes showed improved VR Reaction Time associated with increases in rCBF in the same three clusters. These findings show that TPH2 T-carriers have an abnormal relationship between rCBF and the efficiency of visual-spatial processing that is exacerbated after a season of high-impact sports in the absence of diagnosable concussion. Such gene-environment interactions associated with behavioral changes after exposure to repetitive HAEs have been unrecognized with current clinical analytical tools and warrant further investigation. Our results demonstrate the importance of considering neurovascular factors along with traumatic axonal injury to study long-term effects of repetitive HAEs.

In vivo intervertebral disc deformation: intratissue strain patterns within adjacent discs during flexion-extension.

The biomechanical function of the intervertebral disc (IVD) is a critical indicator of tissue health and pathology. The mechanical responses (displacements, strain) of the IVD to physiologic movement can be spatially complex and depend on tissue architecture, consisting of distinct compositional regions and integrity; however, IVD biomechanics are predominately uncharacterized in vivo. Here, we measured voxel-level displacement and strain patterns in adjacent IVDs in vivo by coupling magnetic resonance imaging (MRI) with cyclic motion of the cervical spine. Across adjacent disc segments, cervical flexion-extension of 10° resulted in first principal and maximum shear strains approaching 10%. Intratissue spatial analysis of the cervical IVDs, not possible with conventional techniques, revealed elevated maximum shear strains located in the posterior disc (nucleus pulposus) regions. IVD structure, based on relaxometric patterns of T2 and T1ρ images, did not correlate spatially with functional metrics of strain. Our approach enables a comprehensive IVD biomechanical analysis of voxel-level, intratissue strain patterns in adjacent discs in vivo, which are largely independent of MRI relaxometry. The spatial mapping of IVD biomechanics in vivo provides a functional assessment of adjacent IVDs in subjects, and provides foundational biomarkers for elastography, differentiation of disease state, and evaluation of treatment efficacy.

Distribution of Head Acceleration Events Varies by Position and Play Type in North American Football.

OBJECTIVE: The goal of this pilot study was to evaluate the number of head acceleration events (HAEs) based on position, play type, and starting stance. DESIGN: Prospective cohort study. SETTING: Postcollegiate skill development camp during practice sessions and 1 exhibition game. PARTICIPANTS: Seventy-eight male adult North American football athletes. INDEPENDENT VARIABLES: A position was assigned to each participant, and plays in the exhibition game were separated by play type for analysis. During the exhibition game, video data were used to determine the effects of the starting position ("up" in a 2-point stance or "down" in a 3- or 4-point stance) on the HAEs experienced by players on the offensive line. MAIN OUTCOME MEASURES: Peak linear acceleration and number of HAEs greater than 20 g (g = 9.81 m/s2) were measured using an xPatch (X2 Biosystems, Seattle, WA). RESULTS: Four hundred thirty-seven HAEs were recorded during practices and 272 recorded during the exhibition game; 98 and 52 HAEs, the greatest number of HAEs by position in the game, were experienced by the offensive and defensive linemen, respectively. Linebackers and tight ends experienced high percentages of HAEs above 60 g. Offensive line players in a down stance had a higher likelihood of sustaining a HAE than players in an up stance regardless of the type of play (run vs pass). CONCLUSIONS: Changing the stance of players on the offensive line and reducing the number of full-contact practices will lower HAEs.

Factors affecting peak impact force during soccer headers and implications for the mitigation of head injuries.

It has been documented that up to 22% of all soccer injuries are concussions. This is in part due to players purposely using their head to direct the ball during play. To provide a more complete understanding of head trauma in soccer athletes, this study characterized the effects of four soccer ball characteristics (size, inflation pressure, mass, velocity) on the resulting peak impact force as it relates to the potential for incurring neurophysiological changes. A total of six hundred trials were performed on size 4 and 5 soccer balls as well as a novel lightweight soccer ball. Impact force was measured with a force plate and ball velocity was determined using motion capture. These data were used, in conjunction with dimensional analysis to relate impact force to ball size, mass, velocity, and pressure. Reasonable reductions in allowable ball parameters resulted in a 19.7% decrease in peak impact force. Adjustments to ball parameters could reduce a high cumulative peak translational acceleration soccer athlete down into a previously defined safer low loading range. In addition, it was noted that water absorption by soccer balls can result in masses that substantially increase impact force and quickly surpass the NCAA weight limit for game play. Additional research is required to determine whether varying soccer ball characteristics will enable soccer players to avoid persistent neurophysiological deficits or what additional interventions may be necessary and the legal implications of these data are discussed.

The Effect of Increasing Fracture Site Stiffness on Bone-Pin Interface Stress and Foot Contact Pressure within the Equine Distal Limb Transfixation Cast: A Finite Element Analysis.

OBJECTIVE: The aim of this study was to determine how increasing stiffness of fracture site tissues distal to the pins in an equine distal limb transfixation cast influences stress at the bone-pin interface, within the bones distal to the transcortical pins, and contact pressure between the foot and the cast. STUDY DESIGN: A transfixation cast finite element model was used to compare the bone-pin interface stress, pin stress, bone stress distal to the pins and contact pressure between the foot and the cast, using six stiffness values for a composite tissue block representing progressive stages of fracture healing. RESULTS: Increasing stiffness of the composite tissue block resulted in a decrease in the maximum stresses at the bone-pin interface, an increase in stresses distal to the transcortical pins and a decrease in the maximum pin stresses. As the composite tissue block stiffness was increased, contact pressure between the bottom of the composite tissue block and the cast increased and the stress patterns surrounding the pin holes became less focal. CONCLUSION: The findings of this study illustrate that with good foot to cast contact within a transfixation cast, increases in tissue stiffness due to progressive fracture healing are expected to reduce bone-pin interface stresses, and increase fracture site loading and stress. Increasing the contact pressure between the foot and the cast could reduce transfixation casting complications such as pin loosening, pin hole fracture and poor fracture healing, if these results transfer to ex vivo and in vivo settings.

Characterizing near-infrared spectroscopy signal under hypercapnia.

Vasoactive stress tests (i.e. hypercapnia, elevated partial pressure of arterial CO2 [PaCO2 ]) are commonly used in functional MRI (fMRI), to induce cerebral blood flow changes and expose hidden perfusion deficits in the brain. Compared with fMRI, near-infrared spectroscopy (NIRS) is an alternative low-cost, real-time, and non-invasive tool, which can be applied in out-of-hospital settings. To develop and optimize vasoactive stress tests for NIRS, several hypercapnia-induced tasks were tested using concurrent-NIRS/fMRI on healthy subjects. The results indicated that the cerebral and extracerebral reactivity to elevated PaCO2 depended on the rate of the CO2 increase. A steep increase resulted in different cerebral and extracerebral reactivities, leading to unpredictable NIRS measurements compared with fMRI. However, a ramped increase, induced by ramped-CO2 inhalation or breath-holding tasks, induced synchronized cerebral, and extracerebral reactivities, resulting in consistent NIRS and fMRI measurements. These results demonstrate that only tasks that increase PaCO2 gradually can produce reliable NIRS results.

Finite deformation elastography of articular cartilage and biomaterials based on imaging and topology optimization.

Tissues and engineered biomaterials exhibit exquisite local variation in stiffness that defines their function. Conventional elastography quantifies stiffness in soft (e.g. brain, liver) tissue, but robust quantification in stiff (e.g. musculoskeletal) tissues is challenging due to dissipation of high frequency shear waves. We describe new development of finite deformation elastography that utilizes magnetic resonance imaging of low frequency, physiological-level (large magnitude) displacements, coupled to an iterative topology optimization routine to investigate stiffness heterogeneity, including spatial gradients and inclusions. We reconstruct 2D and 3D stiffness distributions in bilayer agarose hydrogels and silicon materials that exhibit heterogeneous displacement/strain responses. We map stiffness in porcine and sheep articular cartilage deep within the bony articular joint space in situ for the first time. Elevated cartilage stiffness localized to the superficial zone is further related to collagen fiber compaction and loss of water content during cyclic loading, as assessed by independent T2 measurements. We additionally describe technical challenges needed to achieve in vivo elastography measurements. Our results introduce new functional imaging biomarkers, which can be assessed nondestructively, with clinical potential to diagnose and track progression of disease in early stages, including osteoarthritis or tissue degeneration.

Mitigating the Consequences of Subconcussive Head Injuries.

Subconcussive head injury represents a pathophysiology that spans the expertise of both clinical neurology and biomechanical engineering. From both viewpoints, the terms injury and damage, presented without qualifiers, are synonymously taken to mean a tissue alteration that may be recoverable. For clinicians, concussion is evolving from a purely clinical diagnosis to one that requires objective measurement, to be achieved by biomedical engineers. Subconcussive injury is defined as subclinical pathophysiology in which underlying cellular- or tissue-level damage (here, to the brain) is not severe enough to present readily observable symptoms. Our concern is not whether an individual has a (clinically diagnosed) concussion, but rather, how much accumulative damage an individual can tolerate before they will experience long-term deficit(s) in neurological health. This concern leads us to look for the history of damage-inducing events, while evaluating multiple approaches for avoiding injury through reduction or prevention of the associated mechanically induced damage.