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- Hernandez, Fidel, et al.
(författare)
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Six Degree-of-Freedom Measurements of Human Mild Traumatic Brain Injury
- 2015
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 43:8, s. 1918-1934
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Tidskriftsartikel (refereegranskat)abstract
- This preliminary study investigated whether direct measurement of head rotation improves prediction of mild traumatic brain injury (mTBI). Although many studies have implicated rotation as a primary cause of mTBI, regulatory safety standards use 3 degree-of-freedom (3DOF) translation-only kinematic criteria to predict injury. Direct 6DOF measurements of human head rotation (3DOF) and translation (3DOF) have not been previously available to examine whether additional DOFs improve injury prediction. We measured head impacts in American football, boxing, and mixed martial arts using 6DOF instrumented mouthguards, and predicted clinician-diagnosed injury using 12 existing kinematic criteria and 6 existing brain finite element (FE) criteria. Among 513 measured impacts were the first two 6DOF measurements of clinically diagnosed mTBI. For this dataset, 6DOF criteria were the most predictive of injury, more than 3DOF translation-only and 3DOF rotation-only criteria. Peak principal strain in the corpus callosum, a 6DOF FE criteria, was the strongest predictor, followed by two criteria that included rotation measurements, peak rotational acceleration magnitude and Head Impact Power (HIP). These results suggest head rotation measurements may improve injury prediction. However, more 6DOF data is needed to confirm this evaluation of existing injury criteria, and to develop new criteria that considers directional sensitivity to injury.
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| 4. |
- Laksari, Kaveh, et al.
(författare)
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Mechanistic Insights into Human Brain Impact Dynamics through Modal Analysis
- 2018
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- Although concussion is one of the greatest health challenges today, our physical understanding of the cause of injury is limited. In this Letter, we simulated football head impacts in a finite element model and extracted the most dominant modal behavior of the brain’s deformation. We showed that the brain’s deformation is most sensitive in low frequency regimes close to 30 Hz, and discovered that for most subconcussive head impacts, the dynamics of brain deformation is dominated by a single global mode. In this Letter, we show the existence of localized modes and multimodal behavior in the brain as a hyperviscoelastic medium. This dynamical phenomenon leads to strain concentration patterns, particularly in deep brain regions, which is consistent with reported concussion pathology.
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| 5. |
- Melani, Rafael D., et al.
(författare)
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The Blood Proteoform Atlas : A reference map of proteoforms in human hematopoietic cells
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6579, s. 411-
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Tidskriftsartikel (refereegranskat)abstract
- Human biology is tightly linked to proteins, yet most measurements do not precisely determine alternatively spliced sequences or posttranslational modifications. Here, we present the primary structures of similar to 30,000 unique proteoforms, nearly 10 times more than in previous studies, expressed from 1690 human genes across 21 cell types and plasma from human blood and bone marrow. The results, compiled in the Blood Proteoform Atlas (BPA), indicate that proteoforms better describe protein-level biology and are more specific indicators of differentiation than their corresponding proteins, which are more broadly expressed across cell types. We demonstrate the potential for clinical application, by interrogating the BPA in the context of liver transplantation and identifying cell and proteoform signatures that distinguish normal graft function from acute rejection and other causes of graft dysfunction.
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- Montanino, Annaclaudia, 1990-, et al.
(författare)
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Subject-specific multiscale analysis of concussion : from macroscopic loads to molecular-level damage
- 2021
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Ingår i: Brain Multiphysics. - : Elsevier BV. - 2666-5220. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Sports concussion is a form of mild traumatic brain injury (mTBI) caused by an impulsive force transmitted to the head. While concussion is recognized as a complex pathophysiological process affecting the brain at multiple scales, the causal link between external load and cellular, molecular level damage in mTBI remains elusive. The present study proposes a multiscale framework to analyze concussion and demonstrates its applicability with a real-life concussion case. The multiscale analysis starts from inputting mouth guard-recorded head kinematic into a detailed finite element (FE) head model tailored to the subject's head and white matter (WM) tract morphology. The resulting WM tract-oriented strains are then extracted and input to histology-informed micromechanical models of corpus callosum subregions with axonal detail to obtain axolemma strains at a subcellular level. By comparing axolemma strains against mechanoporation thresholds obtained via molecular dynamics (MD) simulations, axonal damage is inferred corresponding to a likelihood of concussion, in line with clinical observation. This novel multiscale framework bridges the organ-to-molecule length scales and accounts both inter- and intra-subject regional variability, providing a new way of non-invasively predicting axonal damage and real-life concussion analysis. The framework may contribute to a better understanding of the mechanistic causes behind concussion. Statement of Significance This study reports a multiscale computational framework for concussion, for the first time revealing a picture of how a global impact to the head measured on the field transfers to the cellular level of axons and finally down to the molecular level. Demonstrated with a real-life concussion case using a detailed and subject-specific head model, the results show molecular level damage corresponds to a likelihood of concussion, in line with clinical observation. An insight into the multiscale mechanical consequences is critical for a better understanding of the complex pathophysiological process affecting the brain at impact, which today are still poorly understood. Analyzing the concussive injury mechanisms the whole way from brains to molecules may also have significant clinical relevance. We show that in a typical injury scenario, the axolemma sustains large enough strains to entail pore formation in the adjoining lipid bilayer. Proration is found to occur in bilayer regions lacking ganglioside lipids, which provides important implications for the treatment of brain injury and other related neurodegenerative diseases.
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| 7. |
- Montanino, Annaclaudia, 1990-, et al.
(författare)
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Subject-specific multiscale analysis of concussion: from ma-croscopic loads to molecular-level damage
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sports concussions are a form of mild TBI caused by an impulsive force transmitted tothe head. Concussion is recognized as a complex pathophysiological process affecting thebrain at multiple scales. However, neuroimaging evidence of brain damage is currentlylacking. In the present study, a multiscale computational approach that could serve asbrain damage evidence was proposed. To outline the applicability of this framework a realconcussion case associated with an alteration of consciousness was studied. In particular,mouthguard-recorded head kinematic was input into a detailed finite element head modeltailored on the subject’s head and white matter tract morphology. Resulting tissue strainswere extracted and projected to obtain tract-oriented strains. These were then input intomicroscale axonal level models representative of the corpus callosum’s subregions to obtainaxonal membrane maximal deformations. By comparing membrane deformations againstpreviously established thresholds, axonal damage could be inferred in the superior genuand anterior midbody. This study is to be seen as a novel exploratory method for theanalysis of concussion and highlights the need for further model personalization effort aswell as characterization of brain tissue composition to better understand the mechanisticcauses behind concussion.
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| 8. |
- Wu, Lyndia C., et al.
(författare)
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Bandwidth and sample rate requirements for wearable head impact sensors
- 2016
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Ingår i: Journal of Biomechanics. - : Elsevier. - 0021-9290 .- 1873-2380. ; 49:13, s. 2918-2924
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Tidskriftsartikel (refereegranskat)abstract
- Wearable inertial sensors measure human head impact kinematics important to the on-going development and validation of head injury criteria. However, sensor specifications have not been scientifically justified in the context of the anticipated field impact dynamics. The objective of our study is to determine the minimum bandwidth and sample rate required to capture the impact frequency response relevant to injury. We used high-bandwidth head impact data as ground-truth measurements, and investigated the attenuation of various injury criteria at lower bandwidths. Given a 10% attenuation threshold, we determined the minimum bandwidths required to study injury criteria based on skull kinematics and brain deformation in three different model systems: helmeted cadaver (no neck), unhelmeted cadaver (no neck), and helmeted dummy impacts (with neck). We found that higher bandwidths are required for unhelmeted impacts in general and for studying strain rate injury criteria. Minimum gyroscope bandwidths of 300 Hz in helmeted sports and 500 Hz in unhelmeted sports are necessary to study strain rate based injury criteria. A minimum accelerometer bandwidth of 500 Hz in unhelmeted sports is necessary to study most injury criteria. Current devices typically sample at 1000 Hz, with gyroscope bandwidths below 200 Hz, which are not always sufficient according to these requirements. With hard contact test conditions, the identified requirements may be higher than most soft contacts on the field, but should be satisfied to capture the worst contact, and often higher risk, scenarios relative to the specific sport or activity. Our findings will help establish standard guidelines for sensor choice and design in traumatic brain injury research.
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| 9. |
- Zhou, Zhou, 1990-, et al.
(författare)
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The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus During Head Impacts
- 2022
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Hippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.
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| 10. |
- Zhou, Zhou, et al.
(författare)
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White matter tract-oriented deformation is dependent on real-time axonal fiber orientation
- 2021
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 38, s. 1730-1745-
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic axonal injury (TAI) is a critical public health issue with its pathogenesis remaining largely elusive. Finite element (FE) head models are promising tools to bridge the gap between mechanical insult, localized brain response, and resultant injury. In particular, the FE-derived deformation along the direction of white matter (WM) tracts (i.e., tract-oriented strain) has been shown to be an appropriate predictor for TAI. However, the evolution of fiber orientation in time during the impact and its potential influence on the tract-oriented strain remains unknown. To address this question, the present study leveraged an embedded element approach to track real-time fiber orientation during impacts. A new scheme to calculate the tract-oriented strain was proposed by projecting the strain tensors from pre-computed simulations along the temporal fiber direction instead of its static counterpart directly obtained from diffuse tensor imaging. The results revealed that incorporating the real-time fiber orientation not only altered the direction but also amplified the magnitude of the tract-oriented strain, resulting in a generally more extended distribution and a larger volume ratio of WM exposed to high deformation along fiber tracts. These effects were exacerbated with the impact severities characterized by the acceleration magnitudes. Results of this study provide insights into how best to incorporate fiber orientation in head injury models and derive the WM tract-oriented deformation from computational simulations
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