Development and Validation of Subject-Specific 3D Human Head Models Based on a Nonlinear Visco-Hyperelastic Constitutive Framework

Computational models of the human head are promising tools for the study and prediction of traumatic brain injuries (TBIs). Most available head models are developed using inputs (i.e., head geometry, material properties, and boundary conditions) derived from ex-vivo experiments on cadavers or animals and employ linear viscoelasticity (LVE)-based constitutive models, which leads to high uncertainty and poor accuracy in capturing the nonlinear response of brain tissue under impulsive loading conditions. To resolve these issues, a framework for the development of fully subject-specific 3D human head models is proposed, in which model inputs are derived from the same living human subject using a comprehensive in-vivo brain imaging protocol, and the viscous dissipation-based visco-hyperelastic constitutive modeling framework is employed. Specifically, brain tissue material properties are derived from in-vivo magnetic resonance elastography (MRE), and full-field strain-response of brain under rapid rotational acceleration is obtained from tagged MRI, which is used for model validation. The constitutive model comprises the Ogden hyperelastic strain energy density and the Upadhyay-Subhash-Spearot viscous dissipation potential. The simulated strain-response is compared with experimental data and with predictions from subject-specific models employing two commonly used LVE-based constitutive models, using a rigorous validation procedure that evaluates agreement in spatial strain distribution, temporal strain evolution, and differences in maximum values of peak and average strain. Results show that the head model developed in this work reasonably captures 3D brain dynamics, and when compared to LVE-based models, provides improvements in the prediction of peak strains and temporal strain evolution.

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A Subject-Specific Musculoskeletal Modeling Framework to Predict In Vivo Mechanics of Total Knee Arthroplasty

Journal of Biomechanical Engineering ◽

10.1115/1.4029258 ◽

2015 ◽

Vol 137 (2) ◽

Cited By ~ 123

Author(s):

Marco A. Marra ◽

Valentine Vanheule ◽

René Fluit ◽

Bart H. F. J. M. Koopman ◽

John Rasmussen ◽

...

Keyword(s):

Knee Kinematics ◽

Contact Forces ◽

Grand Challenge ◽

Modeling Framework ◽

Trial Simulation ◽

Subject Specific ◽

Joint Contact ◽

Total Knee ◽

The Right

Musculoskeletal (MS) models should be able to integrate patient-specific MS architecture and undergo thorough validation prior to their introduction into clinical practice. We present a methodology to develop subject-specific models able to simultaneously predict muscle, ligament, and knee joint contact forces along with secondary knee kinematics. The MS architecture of a generic cadaver-based model was scaled using an advanced morphing technique to the subject-specific morphology of a patient implanted with an instrumented total knee arthroplasty (TKA) available in the fifth “grand challenge competition to predict in vivo knee loads” dataset. We implemented two separate knee models, one employing traditional hinge constraints, which was solved using an inverse dynamics technique, and another one using an 11-degree-of-freedom (DOF) representation of the tibiofemoral (TF) and patellofemoral (PF) joints, which was solved using a combined inverse dynamic and quasi-static analysis, called force-dependent kinematics (FDK). TF joint forces for one gait and one right-turn trial and secondary knee kinematics for one unloaded leg-swing trial were predicted and evaluated using experimental data available in the grand challenge dataset. Total compressive TF contact forces were predicted by both hinge and FDK knee models with a root-mean-square error (RMSE) and a coefficient of determination (R2) smaller than 0.3 body weight (BW) and equal to 0.9 in the gait trial simulation and smaller than 0.4 BW and larger than 0.8 in the right-turn trial simulation, respectively. Total, medial, and lateral TF joint contact force predictions were highly similar, regardless of the type of knee model used. Medial (respectively lateral) TF forces were over- (respectively, under-) predicted with a magnitude error of M < 0.2 (respectively > −0.4) in the gait trial, and under- (respectively, over-) predicted with a magnitude error of M > −0.4 (respectively < 0.3) in the right-turn trial. Secondary knee kinematics from the unloaded leg-swing trial were overall better approximated using the FDK model (average Sprague and Geers' combined error C = 0.06) than when using a hinged knee model (C = 0.34). The proposed modeling approach allows detailed subject-specific scaling and personalization and does not contain any nonphysiological parameters. This modeling framework has potential applications in aiding the clinical decision-making in orthopedics procedures and as a tool for virtual implant design.

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Subject-Specific Finite Element Modelling of the Human Hand Complex: Muscle-Driven Simulations and Experimental Validation

Annals of Biomedical Engineering ◽

10.1007/s10439-019-02439-2 ◽

2019 ◽

Vol 48 (4) ◽

pp. 1181-1195 ◽

Cited By ~ 1

Author(s):

Yuyang Wei ◽

Zhenmin Zou ◽

Guowu Wei ◽

Lei Ren ◽

Zhihui Qian

Keyword(s):

Finite Element ◽

Contact Pressure ◽

Material Properties ◽

Finite Element Modelling ◽

Human Hand ◽

Fe Model ◽

Muscle Forces ◽

Element Modelling ◽

Subject Specific

AbstractThis paper aims to develop and validate a subject-specific framework for modelling the human hand. This was achieved by combining medical image-based finite element modelling, individualized muscle force and kinematic measurements. Firstly, a subject-specific human hand finite element (FE) model was developed. The geometries of the phalanges, carpal bones, wrist bones, ligaments, tendons, subcutaneous tissue and skin were all included. The material properties were derived from in-vivo and in-vitro experiment results available in the literature. The boundary and loading conditions were defined based on the kinematic data and muscle forces of a specific subject captured from the in-vivo grasping tests. The predicted contact pressure and contact area were in good agreement with the in-vivo test results of the same subject, with the relative errors for the contact pressures all being below 20%. Finally, sensitivity analysis was performed to investigate the effects of important modelling parameters on the predictions. The results showed that contact pressure and area were sensitive to the material properties and muscle forces. This FE human hand model can be used to make a detailed and quantitative evaluation into biomechanical and neurophysiological aspects of human hand contact during daily perception and manipulation. The findings can be applied to the design of the bionic hands or neuro-prosthetics in the future.

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Subject-Specific p-FE Analysis of the Proximal Femur Utilizing Micromechanics-Based Material Properties

International Journal for Multiscale Computational Engineering ◽

10.1615/intjmultcompeng.v6.i5.70 ◽

2008 ◽

Vol 6 (5) ◽

pp. 483-498 ◽

Cited By ~ 23

Author(s):

Zohar Yosibash ◽

Nir Trabelsi ◽

Christian Hellmich

Keyword(s):

Proximal Femur ◽

Material Properties ◽

Fe Analysis ◽

Subject Specific

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Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain

Current Drug Delivery ◽

10.2174/1567201816666190619122456 ◽

2019 ◽

Vol 16 (7) ◽

pp. 637-644 ◽

Cited By ~ 4

Author(s):

Hadas Han ◽

Sara Eyal ◽

Emma Portnoy ◽

Aniv Mann ◽

Miriam Shmuel ◽

...

Keyword(s):

Brain Tissue ◽

Ex Vivo ◽

In Vivo Studies ◽

Nanoparticle Distribution ◽

Spontaneous Seizures ◽

Systemic Distribution ◽

Hippocampal Ca1 ◽

Pilocarpine Model

Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.

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Protein Kinase A Distribution in Meningioma

Cancers ◽

10.3390/cancers11111686 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1686 ◽

Cited By ~ 1

Author(s):

Caretta ◽

Denaro ◽

D’Avella ◽

Mucignat-Caretta

Keyword(s):

Brain Tissue ◽

Catalytic Subunit ◽

Therapeutic Interventions ◽

Normal Brain ◽

Local Concentration ◽

Correlation Pattern ◽

Catalytic Subunits ◽

Tissue Specimens ◽

Pka Catalytic Subunit

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions.

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An experimental method for evaluating constitutive models of myocardium in in vivo hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.2.h853 ◽

1994 ◽

Vol 267 (2) ◽

pp. H853-H863 ◽

Cited By ~ 5

Author(s):

L. L. Creswell ◽

M. J. Moulton ◽

S. G. Wyers ◽

J. S. Pirolo ◽

D. S. Fishman ◽

...

Keyword(s):

Experimental Method ◽

Diastolic Pressure ◽

Constitutive Models ◽

Fe Analysis ◽

Small Displacement ◽

Ventricular Wall ◽

Canine Heart ◽

Unknown Parameters ◽

Tissue Tagging

A new experimental method for the evaluation of myocardial constitutive models combines magnetic resonance (MR) radiofrequency (RF) tissue-tagging techniques with iterative two-dimensional (2-D) nonlinear finite element (FE) analysis. For demonstration, a nonlinear isotropic constitutive model for passive diastolic expansion in the in vivo canine heart is evaluated. A 2-D early diastolic FE mesh was constructed with loading parameters for the ventricular chambers taken from mean early diastolic-to-late diastolic pressure changes measured during MR imaging. FE solution was performed for regional, intramyocardial ventricular wall strains using small-strain, small-displacement theory. Corresponding regional ventricular wall strains were computed independently using MR images that incorporated RF tissue tagging. Two unknown parameters were determined for an exponential strain energy function that maximized agreement between observed (from MR) and predicted (from FE analysis) regional wall strains. Extension of this methodology will provide a framework in which to evaluate the quality of myocardial constitutive models of arbitrary complexity on a regional basis.

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Predicting chromosome damage in astronauts participating in international space station missions

Scientific Reports ◽

10.1038/s41598-021-84242-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alan Feiveson ◽

Kerry George ◽

Mark Shavers ◽

Maria Moreno-Villanueva ◽

Ye Zhang ◽

...

Keyword(s):

International Space Station ◽

Dose Response ◽

Ex Vivo ◽

Space Station ◽

Space Radiation ◽

Blood Samples ◽

International Space ◽

Significant Difference ◽

Subject Specific

AbstractSpace radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose–response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose–response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.

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In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.5.1091 ◽

1999 ◽

Vol 43 (5) ◽

pp. 1091-1097 ◽

Cited By ~ 7

Author(s):

Hideki Kita ◽

Hirotami Matsuo ◽

Hitomi Takanaga ◽

Junichi Kawakami ◽

Koujirou Yamamoto ◽

...

Keyword(s):

Brain Tissue ◽

Threshold Concentration ◽

Current Response ◽

Drug Induced ◽

Inhibition Ratio ◽

New Quinolones ◽

The Central Nervous System ◽

Anti Inflammatory

ABSTRACT We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the γ-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 μM) > FRP (0.3 μM) > FLB (0.2 μM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

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