Alterations in the Magnetoencephalography Default Mode Effective Connectivity following Concussion.

BACKGROUND AND PURPOSE: Magnetoencephalography is sensitive to functional connectivity changes associated with concussion. However, the directional influences between functionally related regions remain unexplored. In this study, we therefore evaluated concussion-related magnetoencephalography-based effective connectivity changes within resting-state default mode network regions. MATERIALS AND METHODS: Resting-state magnetoencephalography was acquired for 8 high school football players with concussion at 3 time points (preseason, postconcussion, postseason), as well as 8 high school football players without concussion and 8 age-matched controls at 2 time points (preseason, postseason). Time-series from the default mode network regions were extracted, and effective connectivity between them was computed for 5 different frequency bands. The default mode network regions were grouped into anterior and posterior default mode networks. The combined posterior-to-anterior and anterior-to-posterior effective connectivity values were averaged to generate 2 sets of values for each subject. The effective connectivity values were compared using a repeated measures ANOVA across time points for the concussed, nonconcussed, and control groups, separately. RESULTS: A significant increase in posterior-to-anterior effective connectivity from preseason to postconcussion (corrected P value = .013) and a significant decrease in posterior-to-anterior effective connectivity from postconcussion to postseason (corrected P value = .028) were observed in the concussed group. Changes in effective connectivity were only significant within the delta band. Anterior-to-posterior connectivity demonstrated no significant change. Effective connectivity in the nonconcussed group and controls did not show significant differences. CONCLUSIONS: The unidirectional increase in effective connectivity postconcussion may elucidate compensatory processes, invoking use of posterior regions to aid the function of susceptible anterior regions following brain injury. These findings support the potential value of magnetoencephalography in exploring directional changes of the brain network following concussion.

Prevalence and Incidence of Microhemorrhages in Adolescent Football Players.

BACKGROUND AND PURPOSE: SWI is an advanced imaging modality that is especially useful in cerebral microhemorrhage detection. Such microhemorrhages have been identified in adult contact sport athletes, and the sequelae of these focal bleeds are thought to contribute to neurodegeneration. The purpose of this study was to utilize SWI to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are significantly greater than those of adolescent noncontact athletes. MATERIALS AND METHODS: Preseason and postseason SWI was performed and evaluated on 78 adolescent football players. SWI was also performed on 27 adolescent athletes who reported no contact sport history. Two separate one-tailed Fisher exact tests were performed to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are greater than those of noncontact athlete controls. RESULTS: Microhemorrhages were observed in 12 football players. No microhemorrhages were observed in any controls. Adolescent football players demonstrated a significantly greater prevalence of microhemorrhages than adolescent noncontact controls (P = .02). Although 2 football players developed new microhemorrhages during the season, microhemorrhage incidence during 1 football season was not statistically greater in the football population than in noncontact control athletes (P = .55). CONCLUSIONS: Adolescent football players have a greater prevalence of microhemorrhages compared with adolescent athletes who have never engaged in contact sports. While microhemorrhage incidence during 1 season is not significantly greater in adolescent football players compared to adolescent controls, there is a temporal association between playing football and the appearance of new microhemorrhages.

Development of Subject-Specific Proximal Femur Finite Element Models Of Older Adults with Obesity to Evaluate the Effects of Weight Loss on Bone Strength.

STUDY BACKGROUND: Recommendation of intentional weight loss in older adults remains controversial, due in part to the loss of bone mineral density (BMD) known to accompany weight loss. While finite element (FE) models have been used to assess bone strength, these methods have not been used to study the effects of weight loss. The purpose of this study is to develop subject-specific FE models of the proximal femur and study the effect of intentional weight loss on bone strength. METHODS: Computed tomography (CT) scans of the proximal femur of 25 overweight and obese (mean BMI=29.7 ± 4.0 kg/m2), older adults (mean age=65.6 ± 4.1 years) undergoing an 18-month intentional weight loss intervention were obtained at baseline and post-intervention. Measures of volumetric BMD (vBMD) and variable cortical thickness were derived from each subject CT scan and directly mapped to baseline and post-intervention models. Subject-specific FE models were developed using morphing techniques. Bone strength was estimated through simulation of a single-limb stance and sideways fall configuration. RESULTS: After weight loss intervention, there were significant decreases from baseline to 18 months in vBMD (total hip: -0.024 ± 0.013 g/cm3; femoral neck: -0.012 ± 0.014 g/cm3), cortical thickness (total hip: -0.044 ± 0.032 mm; femoral neck: -0.026 ± 0.039 mm), and estimated strength (stance: -0.15 ± 0.12 kN; fall: -0.04 ± 0.06 kN). Adjusting for baseline bone measures, body mass, and gender, correlations were found between weight change and change in total hip and femoral neck cortical thickness (all p<0.05). For every 1 kilogram of body mass lost cortical thickness in the total hip and femoral neck decreased by 0.003 mm and 0.004 mm, respectively. No significant correlations were present for the vBMD or strength data. CONCLUSION: The developed subject-specific FE models could be used to better understand the effects of intentional weight loss on bone health.

A paradigm for human body finite element model integration from a set of regional models.

Computational modeling offers versatility, scalability, and cost advantages to researchers in the trauma and injury biomechanics communities. The Global Human Body Models Consortium (GHBMC) is a group of government, industry, and academic researchers developing human body models (HBMs) that aim to become the standard tool to meet this growing research need. The objective of this study is to present the methods used to develop the average seated male occupant model (M50, weight = 78 kg, height = 175 cm) from five separately validated body region models (BRMs). BRMs include the head, neck, thorax, abdomen, and a combined pelvis and lower extremity model. Modeling domains were split at the atlanto-occipital joint, C7-T1 boundary, diaphragm, abdominal cavity (peritoneum/retroperitoneum), and the acetabulum respectively. BRM meshes are based on a custom CAD model of the seated male built from a multi-modality imaging protocol of a volunteer subject found in literature.[1] Various meshing techniques were used to integrate the full body model (FBM) including 1-D beam and discrete element connections (e.g. ligamentous structures), 2D shell nodal connections (e.g. inferior vena cava to right atrium), 3D hexahedral nodal connections (e.g. soft tissue envelope connections between regions), and contact definitions varying from tied (muscle insertions) to sliding (liver and diaphragm contact). The model was developed in a general-purpose finite element code, LS-Dyna (LTSC, Livermore, CA) R4.2.1., and consists of 1.95 million elements and 1.3 million nodes. The element breakdown by type is 41% hexahedral, 33.7% tetrahedral, 19.5% quad shells and 5% tria shell. The integration methodology presented highlights the viability of using a collaborative development paradigm for the construction of HBMs, and will be used as template for expanding the suite of GHBMC models.

Development of a full body CAD dataset for computational modeling: a multi-modality approach.

The objective of this study was to develop full body CAD geometry of a seated 50th percentile male. Model development was based on medical image data acquired for this study, in conjunction with extensive data from the open literature. An individual (height, 174.9 cm, weight, 78.6 ± 0.77 kg, and age 26 years) was enrolled in the study for a period of 4 months. 72 scans across three imaging modalities (CT, MRI, and upright MRI) were collected. The whole-body dataset contains 15,622 images. Over 300 individual components representing human anatomy were generated through segmentation. While the enrolled individual served as a template, segmented data were verified against, or augmented with, data from over 75 literature sources on the average morphology of the human body. Non-Uniform Rational B-Spline (NURBS) surfaces with tangential (G1) continuity were constructed over all the segmented data. The sagittally symmetric model consists of 418 individual components representing bones, muscles, organs, blood vessels, ligaments, tendons, cartilaginous structures, and skin. Length, surface area, and volumes of components germane to crash injury prediction are presented. The total volume (75.7 × 103 cm(3)) and surface area (1.86 × 102 cm(2)) of the model closely agree with the literature data. The geometry is intended for subsequent use in nonlinear dynamics solvers, and serves as the foundation of a global effort to develop the next-generation computational human body model for injury prediction and prevention.

Reducing chest injuries in automobile collisions: rib fracture timing and implications for thoracic injury criteria.

The purpose of this study was to quantify the biomechanical response of the human thorax during dynamic shoulder belt loading representative of that seen in a severe automotive collision. Two post-mortem human surrogates (PMHSs) (one male and one female) were instrumented with 26 single-axis strain gages on the ribs, sternum, and clavicle. The thorax of each PMHS was placed on a custom spine support bracket designed to support the thorax on either side of the spinous process, thereby allowing free motion at the costovertebral joints. In addition, the support bracket raised the thorax above the flat base plate, which could otherwise constrain the deformation and motion of the posterior region of the rib cage. The thorax of each PMHS was then loaded using a custom table-top belt loading system that generated thoracic displacement rates representative of a severe automotive collision, 1.3 m/s for the male PMHS and 1.0 m/s for the female PMHS. The rib fracture timing data, determined by analyzing the strain gage time histories, showed that severe thoracic injury (AIS = 3) occurred at 16% chest compression for the male and 12% chest compression for the female. However, these values are well below the current thoracic injury criteria of 29% chest compression for the male and 23% chest compression for the female. This data illustrates that serious thoracic injury (AIS = 3) occurs at lower chest compressions than the current ATD thoracic injury criteria. Overall, this study provides critical data that can be used in the design and validation of advanced ATDs and finite element models, as well as the establishment of improved, more stringent thoracic injury criteria.

Rib fracture timing in dynamic belt tests with human cadavers.

The purpose of this article is to present data from dynamic belt loading tests on the thorax of human cadavers where the exact timing of all rib fractures is known. To quantify rib fracture timing, a total of 47 strain gages were placed throughout the thorax of two human cadavers (one male, one female). To simulate thoracic loading observed in a severe car crash, a custom table-top belt loading device was developed. The belt loading pulse was configured to result in approximately 40% chest compression during a 150 ms load and unload cycle. The time histories of each strain gage were analyzed to determine the time of each rib fracture which was then directly compared with the reaction loads and chest displacements at that exact time, thereby creating a noncensored data set. In both cadavers, all rib fractures occurred within the first 35% compression of the thorax. As a general trend, fractures on the left side of the thorax, where the passenger belt passed over the abdomen, occurred first followed by fractures to the upper ribs on the right side of the thorax. By utilizing this technique, the exact timing of each injury level can be characterized relative to the mechanical parameters. For example, using rib fractures as the parameter for Abbreviated Injury Scale (AIS) scores in the female test, it was shown that AIS 1 injury occurred at a chest compression of 21.1%, AIS 2 at 21.6%, AIS 3 at 22.0%, and AIS 4 at 33.3%.

Retrospective identification of subject anthropometry using computed tomography of the leg.

Lower extremity injuries from car crashes are associated with decreased quality of life. To better evaluate the forces seen by the lower extremity during car crashes accurate models of the lower extremities must be created. This effort is motivated by a need to identify CT scans of a 5th female and a 50th and 95th male leg for use in finite element model development. Our goal is to outline a method for obtaining retrospective data on skeletal anthropometry and relate this data to the population when subject anthropometry is unavailable. Landmark data was collected from axial slices of lower extremity CT scans without skeletal pathology and CT scout films. The two methods used to collect data were compared and published data was used to create normal distribution curves for the leg lengths of males and females across the adult population. Knowledge of how lower extremity geometry quantitatively relates to subject height was also used to find patient scans representing lower extremity lengths of the 5th female, and 50th and 95th percentile male standard models. From the data collected on the two methods we found that CT 3-D reconstructions are superior for assessing length compared to using CT scouts. This methodology is useful for mining the large database of clinical patient scans retrospectively to create models that can predict injury in humans of all shapes and sizes.

Hsp104 is a highly conserved protein with two essential nucleotide-binding sites.

Most eukaryotic cells produce proteins with relative molecular masses in the range of 100,000 to 110,000 after exposure to high temperatures. These proteins have been studied only in yeast and mammalian cells. In Saccharomyces cerevisiae, heat-shock protein hsp104 is vital for tolerance to heat, ethanol and other stresses. The mammalian hsp110 protein is nucleolar and redistributes with growth state, nutritional conditions and heat shock. The relationships between hsp110, hsp104 and the high molecular mass heat-shock proteins of other organisms were unknown. We report here that hsp104 is a member of the highly conserved ClpA/ClpB protein family first identified in Escherichia coli and that additional heat-inducible members of this family are present in Schizosaccharomyces pombe and in mammals. Mutagenesis of two putative nucleotide-binding sites in hsp104 indicates that both are essential for function in thermotolerance.