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Mulugeta, L.

Publications and source records attributed to Mulugeta, L..

Probabilistic Modeling Of Ocular Biomechanics In VIIP: Risk Stratification

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a major health concern for long-duration space missions. Currently, it is thought that a cephalad fluid shift in microgravity causes elevated intracranial pressure (ICP) that is transmitted along the optic nerve sheath (ONS). We hypothesize that this in turn leads to alteration and remodeling of connective tissue in the posterior eye which impacts vision. Finite element (FE) analysis is a powerful tool for examining the effects of mechanical loads in complex geometries. Our goal is to build a FE analysis framework to understand the response of the lamina cribrosa and optic nerve head to elevations in ICP in VIIP. To simulate the effects of different pressures on tissues in the posterior eye, we developed a geometric model of the posterior eye and optic nerve sheath and used a Latin hypercubepartial rank correlation coef-ficient (LHSPRCC) approach to assess the influence of uncertainty in our input parameters (i.e. pressures and material properties) on the peak strains within the retina, lamina cribrosa and optic nerve. The LHSPRCC approach was repeated for three relevant ICP ranges, corresponding to upright and supine posture on earth, and microgravity [1]. At each ICP condition we used intraocular pressure (IOP) and mean arterial pressure (MAP) measurements of in-flight astronauts provided by Lifetime Surveillance of Astronaut Health Program, NASA Johnson Space Center. The lamina cribrosa, optic nerve, retinal vessel and retina were modeled as linear-elastic materials, while other tissues were modeled as a Mooney-Rivlin solid (representing ground substance, stiffness parameter c1) with embedded collagen fibers (stiffness parameters c3, c4 and c5). Geometry creationmesh generation was done in Gmsh [2], while FEBio was used for all FE simulations [3]. The LHSPRCC approach resulted in correlation coefficients in the range of 1. To assess the relative influence of the uncertainty in an input parameter on the peak strains, we ranked and then normalized these coefficients, considering that normalized values 0.5 implied a substantial influence on the range of the peak strains in the optic nerve head (ONH). IOP and ICP were found to have a major influence on the peak strains in the ONH, as did optic nerve and LC stiffness. Interestingly, the stiffness of the sclera far from the scleral canal did not have a large influence on peak strains in ONH tissues; however, the collagen fiber stiffness in the peripapillary sclera and annular ring both influenced the peak strains within the ONH. We have created a physiologically relevant model that incorporated collagen fibers to study the effects of elevated ICP. Elevated ICP resulted in strains in the optic nerve that are not predicted to occur on earth: the upright or supine conditions. We found that IOP, ICP, lamina cribrosa stiffness and optic nerve stiffness had the highest association with these extreme strains in the ONH. These extreme strains may activate mechanosensitive cells that induce tissue remodeling and are a risk factor for the development of VIIP.

biomechanics

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

gravitational physiology

Modeling the Effects of Spaceflight on the Posterior Eye in VIIP

Purpose: Visual Impairment and Intracranial Pressure (VIIP) syndrome is a new and significant health concern for long-duration space missions. Its etiology is unknown, but is thought to involve elevated intracranial pressure (ICP)that induces connective tissue changes and remodeling in the posterior eye (Alexander et al. 2012). Here we study the acute biomechanical response of the lamina cribrosa (LC) and optic nerve to elevations in ICP utilizing finite element (FE) modeling. Methods: Using the geometry of the posterior eye from previous axisymmetric FE models (Sigal et al. 2004), we added an elongated optic nerve and optic nerve sheath, including the pia and dura. Tissues were modeled as linear elastic solids. Intraocular pressure and central retinal vessel pressures were set at 15 mmHg and 55 mmHg, respectively. ICP varied from 0 mmHg (suitable for standing on earth) to 30 mmHg (representing severe intracranial hypertension, thought to occur in space flight). We focused on strains and deformations in the LC and optic nerve (within 1 mm of the LC) since we hypothesize that they may contribute to vision loss in VIIP. Results: Elevating ICP from 0 to 30 mmHg significantly altered the strain distributions in both the LC and optic nerve (Figure), notably leading to more extreme strain values in both tension and compression. Specifically, the extreme (95th percentile) tensile strains in the LC and optic nerve increased by 2.7- and 3.8-fold, respectively. Similarly, elevation of ICP led to a 2.5- and 3.3-fold increase in extreme (5th percentile) compressive strains in the LC and optic nerve, respectively. Conclusions: The elevated ICP thought to occur during spaceflight leads to large acute changes in the biomechanical environment of the LC and optic nerve, and we hypothesize that such changes can activate mechanosensitive cells and invoke tissue remodeling. These simulations provide a foundation for more comprehensive studies of microgravity effects on human vision, e.g. to guide biological studies in which cells and tissues are mechanically loaded in a ranger elevant for microgravity conditions.

gravitational physiology

Lumped Parameter Models of the Central Nervous System for VIIP Research

INTRODUCTION: Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit, such as to Mars and asteroids, expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome [1]. It has been hypothesized that the headward shift of cerebral spinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn induces VIIP syndrome through biomechanical pathways [1, 2]. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the realted IWS abstracts submitted by Nelson et al., Feola et al. and Ethier et al. METHODS: We have developed a nine compartment CNS model (Figure 1) capable of both time-dependent and steady state fluid transport simulations, based on the works of Stevens et al. [3]. The breakdown of compartments within the model includes: vascular (3), CSF (2), brain (1) and extracranial (3). The boundary pressure in the Central Arteries [A] node is prescribed using an oscillating pressure function PA(t) simulating the carotid pulsatile pressure wave as developed by Linninger et al. [4]. For each time step, pressures are integrated through time using an adaptive-timestep 4th and 5th order Runga-Kutta solver. Once pressures are found, constitutive equations are used to solve for flowrates (Q) between each compartment. In addition to fluid flow between the different compartments, compliance (C) interactions between neighboring compartments are represented. We are also developing a second CNS model based on the works of Linninger et al. [4] which takes a more granular approach to represent the interactions of the intracranial and spinal compartments with the inclusion of arteries, arterioles, capillaries, venules, veins, venous sinus, and ventricles. The flow through the arteries, veins and CSF compartments are governed by continuity, momentum and distensibility balance equations. Furthermore, unlike the Stevens et al. approach, the Monro-Kellie doctrine of constant cranial volume and the bi-phasic nature of the brain parenchyma are implemented. These features appear to be more consistent with the physiologic and anatomical behavior of the CNS, and follow a modeling philosophy similar to the lumped parameter eye model that is intended to be integrated with the CNS model. However, Linninger’s approach has never been implemented to include hydrostatic gradient and microgravity simulation capabilities. Therefore, we aim at implement this modeling approach for spaceflight simulations and assess its overall applicability to VIIP research. OBJECTIVES: We will present verification and validation test results for both models, as well as head-to-head comparison to explore their strengths and limitations with respect to mathematical implementation and physiological significance for VIIP research. In doing so, we hope to provide some guidance to the HRP research community on how to appropriately leverage lumped parameter models for space biomedical research.

Vera, J.

Computational Modeling Using OpenSim to Simulate a Squat Exercise Motion

Long duration space travel to destinations such as Mars or an asteroid will expose astronauts to extended periods of reduced gravity. Astronauts will use an exercise regime for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Since the area available in the spacecraft for an exercise device is limited and gravity is not present to aid loading, compact resistance exercise device prototypes are being developed. Since it is difficult to rigorously test these proposed devices in space flight, computational modeling provides an estimation of the muscle forces, joint torques and joint loads during exercise to gain insight on the efficacy to protect the musculoskeletal health of astronauts.

Human Factors Engineering

Numerical Modeling of Ophthalmic Response to Space

To investigate ophthalmic changes in spaceflight, we would like to predict the impact of blood dysregulation and elevated intracranial pressure (ICP) on Intraocular Pressure (IOP). Unlike other physiological systems, there are very few lumped parameter models of the eye. The eye model described here is novel in its inclusion of the human choroid and retrobulbar subarachnoid space (rSAS), which are key elements in investigating the impact of increased ICP and ocular blood volume. Some ingenuity was required in modeling the blood and rSAS compartments due to the lack of quantitative data on essential hydrodynamic quantities, such as net choroidal volume and blood flowrate, inlet and exit pressures, and material properties, such as compliances between compartments.

intracranial pressure

An Integrated Model of the Cardiovascular and Central Nervous Systems for Analysis of Microgravity Induced Fluid Redistribution

A recognized side effect of prolonged microgravity exposure is visual impairment and intracranial pressure (VIIP) syndrome. The medical understanding of this phenomenon is at present preliminary, although it is hypothesized that the headward shift of bodily fluids in microgravity may be a contributor. Computational models can be used to provide insight into the origins of VIIP. In order to further investigate this phenomenon, NASAs Digital Astronaut Project (DAP) is developing an integrated computational model of the human body which is divided into the eye, the cerebrovascular system, and the cardiovascular system. This presentation will focus on the development and testing of the computational model of an integrated model of the cardiovascular system (CVS) and central nervous system (CNS) that simulates the behavior of pressures, volumes, and flows within these two physiological systems.

Space Adaptation Syndrome

Development of the NASA Digital Astronaut Project Muscle Model

This abstract describes development work performed on the NASA Digital Astronaut Project Muscle Model. Muscle atrophy is a known physiological response to exposure to a low gravity environment. The DAP muscle model computationally predicts the change in muscle structure and function vs. time in a reduced gravity environment. The spaceflight muscle model can then be used in biomechanical models of exercise countermeasures and spaceflight tasks to: 1) develop site specific bone loading input to the DAP bone adaptation model over the course of a mission; 2) predict astronaut performance of spaceflight tasks; 3) inform effectiveness of new exercise countermeasures concepts.

Mathematical Models

Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

Mulugeta, L.

Verification, Validation and Credibility Assessment of a Computational Model of the Advanced Resistive Exercise Device (ARED)

The Advanced Resistive Exercise Device (ARED) is the resistive exercise device used by astronauts on the International Space Station (ISS) to mitigate bone loss and muscle atrophy due to extended exposure to microgravity (micro g). The Digital Astronaut Project (DAP) has developed a multi-body dynamics model of biomechanics models for use in spaceflight exercise physiology research and operations. In an effort to advance model maturity and credibility of the ARED model, the DAP performed verification, validation and credibility (VV and C) assessment of the analyses of the model in accordance to NASA-STD-7009 'Standards for Models and Simulations'.

Werner, C. R.

A Framework for Modelling Connective Tissue Changes in VIIP Syndrome

Insertion of astronauts into microgravity induces a cascade of physiological adaptations, notably including a cephalad fluid shift. Longer-duration flights carry an increased risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. The slow onset of changes in VIIP, their chronic nature, and the similarity of certain clinical features of VIIP to ophthalmic findings in patients with raised intracranial pressure strongly suggest that: (i) biomechanical factors play a role in VIIP, and (ii) connective tissue remodeling must be accounted for if we wish to understand the pathology of VIIP. Our goal is to elucidate the pathophysiology of VIIP and suggest countermeasures based on biomechanical modeling of ocular tissues, suitably informed by experimental data, and followed by validation and verification. We specifically seek to understand the quasi-homeostatic state that evolves over weeks to months in space, during which ocular tissue remodeling occurs. This effort is informed by three bodies of work: (i) modeling of cephalad fluid shifts; (ii) modeling of ophthalmic tissue biomechanics in glaucoma; and (iii) modeling of connective tissue changes in response to biomechanical loading.

microgravity

The Digital Astronaut Project Bone Remodeling Model

One of the main objectives is to provide a tool to help HHC address Bone Gap Osteo 4: We don't know the contribution of each risk factor on bone loss and recovery of bone strength and which factors are the best targets for countermeasure application; and Osteo7: We need to identify options for mitigation of early onset osteoporosis before, during, and after spaceflight.

Pennline, J. A.

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the development of the Adams ARED module including its capabilities, limitations, and assumptions. Preliminary results, validation activities, and a practical application of the module to inform the relative effect of the flywheels on exercise will be discussed.

Humphreys, B. T.

Musculoskeletal Modeling Component of the NASA Digital Astronaut Project

The NASA Digital Astronaut Project s (DAP) objective is to provide computational tools that support research of the physiological response to low gravity environments and analyses of how changes cause health and safety risks to the astronauts and to the success of the mission. The spaceflight risk associated with muscle atrophy is impaired performance due to reduced muscle mass, strength and endurance. Risks of early onset of osteoporosis and bone fracture are among the spaceflight risks associated with loss of bone mineral density. METHODS: Tools under development include a neuromuscular model, a biomechanical model and a bone remodeling model. The neuromuscular model will include models of neuromuscular drive, muscle atrophy, fiber morphology and metabolic processes as a function of time in space. Human movement will be modeled with the biomechanical model, using muscle and bone model parameters at various states. The bone remodeling model will allow analysis of bone turnover, loss and adaptation. A comprehensive trade study was completed to identify the current state of the art in musculoskeletal modeling. The DAP musculoskeletal models will be developed using a combination of existing commercial software and academic research codes identified in the study, which will be modified for use in human spaceflight research. These individual models are highly dependent upon each other and will be integrated together once they reach sufficient levels of maturity. ANALYSES: The analyses performed with these models will include comparison of different countermeasure exercises for optimizing effectiveness and comparison of task requirements and the state of strength and endurance of a crew member at a particular time in a mission. DISCUSSION: The DAP musculoskeletal model has the potential to complement research conducted on spaceflight induced changes to the musculoskeletal system. It can help with hypothesis formation, identification of causative mechanisms and supplementing small data samples.

Lewandowski, B. E.