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Myers, J. G.

Publications and source records attributed to Myers, J. G..

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2018

Cross-Cutting Computational Modeling Project: Integrative Modeling Approach

A wide range of computational models and analyses have been applied to spaceflight risk assessment and countermeasure development. The benefits of using computational modeling to enhance Human Research Program (HRP) goals include the ability to mathematically represent physiological systems, integrate multiple, discrete experimental measures, span multiple temporal and spatial scales, determine important factors within the system and provide estimates of unmeasurable quantities. In the area of application, computational models provide a means of developing simulations to test hypotheses, determining key factors of the system to aid experimental design and bridging gaps in sparse data by mathematically simulating large populations. Specifically, computational models and their supporting analysis tools have the proven potential to integrate analyses of risk factors to enhance mission planning and preparation capabilities and to inform spacecraft design and countermeasure development. Appropriately applied, computational models may allow intelligent, unbiased physiological parameter assessment to enable hypothesis testing and model based design of experiments. HRP recently formed the Computational Modeling Project (CMP), managed out of Glenn Research Center, as a cross-cutting activity aimed at leveraging the growing power and acceptance of computational modeling in informing clinical, physiological, and biological studies. This presentation will provide an overview of the challenges and opportunities in implementing various forms of computational models in support of the HRPs path to risk reduction.

biomechanics↗
NASA NTRS2017

Computational Modeling of Space Physiology for Informing Spaceflight Countermeasure Design and Predictions of Efficacy

MOTIVATION: Spaceflight countermeasures mitigate the harmful effects of the space environment on astronaut health and performance. Exercise has historically been used as a countermeasure to physical deconditioning, and additional countermeasures including lower body negative pressure, blood flow occlusion and artificial gravity are being researched as countermeasures to spaceflight-induced fluid shifts. The NASA Digital Astronaut Project uses computational models of physiological systems to inform countermeasure design and to predict countermeasure efficacy.OVERVIEW: Computational modeling supports the development of the exercise devices that will be flown on NASAs new exploration crew vehicles. Biomechanical modeling is used to inform design requirements to ensure that exercises can be properly performed within the volume allocated for exercise and to determine whether the limited mass, volume and power requirements of the devices will affect biomechanical outcomes. Models of muscle atrophy and bone remodeling can predict device efficacy for protecting musculoskeletal health during long-duration missions. A lumped-parameter whole-body model of the fluids within the body, which includes the blood within the cardiovascular system, the cerebral spinal fluid, interstitial fluid and lymphatic system fluid, estimates compartmental changes in pressure and volume due to gravitational changes. These models simulate fluid shift countermeasure effects and predict the associated changes in tissue strain in areas of physiological interest to aid in predicting countermeasure effectiveness. SIGNIFICANCE: Development and testing of spaceflight countermeasure prototypes are resource-intensive efforts. Computational modeling can supplement this process by performing simulations that reduce the amount of necessary experimental testing. Outcomes of the simulations are often important for the definition of design requirements and the identification of factors essential in ensuring countermeasure efficacy.

biomedical data↗
NASA NTRS2017

Modeling Microgravity Induced Fluid Redistribution Autoregulatory and Hydrostatic Enhancements

Space flight induces a marked cephalad (headward) redistribution of blood and interstitial fluid potentially resulting in a loss of venous tone and reduction in heart muscle efficiency upon introduction into the microgravity environment. Using various types of computational models, we are investigating how this fluid redistribution may induce intracranial pressure changes, relevant to reported reductions in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome. Methods: We utilize a lumped parameter cardiovascular system (CVS) model, augmented by compartments comprising the cerebral spinal fluid (CSF) space, as the primary tool to describe how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. Models of ocular fluid pressures and biomechanics then accept the output of the above model as boundary condition input to allow more detailed, local analysis (see IWS Abstract by Ethier et al.). Recently, we enhanced the capabilities our previously reported CVS model through the implementation of robust autoregulatory mechanisms and a more fundamental approach to the implementation of hydrostatic mechanisms. Modifying the approach of Blanco et al., we implemented auto-regulation in a quasi-static manner, as an averaged effect across the span of one heartbeat. This approach reduced the higher frequency perturbations from the regulatory mechanism and was intended to allow longer simulation times (days) than models that implement within-beat regulatory mechanisms (minutes). A more fundamental approach to hydrostatics was implemented by a quasi-1D approach, in which compartment descriptions include compartment length, orientation and relative position, allowed for modeling of body orientation, relative body positioning and, in the future, alternative gravity environments. At this time the inclusion of hydrostatic mechanisms supplies additional capabilities to train and validate the CVS model with terrestrial data. Results and Conclusions: With the implementation of auto-regulation and hydrostatic modeling capabilities, the model performs as expected in the maintaining the CA (Central Artery) compartment pressure when simulating orientations ranging from supine to standing. The model appears to generally overpredict heart rate and thus cardiac output, possibly indicating sensitivity to the nominal heart rate, which is used as an initial set point of the regulation mechanisms. Despite this sensitivity, the model performs consistently for many hours of simulation time, indicating the success of our quasi-static implementation approach.

biomechanics↗
NASA NTRS2017

Integrated Model of the Eye/Optic Nerve Head Biomechanical Environment

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Previously, it has been suggested that ocular changes observed in VIIP syndrome are related to the cephalad fluid shift that results in altered fluid pressures [1]. We are investigating the impact of changes in intracranial pressure (ICP) using a combination of numerical models, which simulate the effects of various environment conditions, including finite element (FE) models of the posterior eye. The specific interest is to understand how altered pressures due to gravitational changes affect the biomechanical environment of tissues of the posterior eye and optic nerve sheath. METHODS: Additional description of the numerical modeling is provided in the IWS abstract by Nelson et al. In brief, to simulate the effects of a cephalad fluid shift on the cardiovascular and ocular systems, we utilized a lumped-parameter compartment model of these systems. The outputs of this lumped-parameter model then inform boundary conditions (pressures) for a finite element model of the optic nerve head (Figure 1). As an example, we show here a simulation of postural change from supine to 15 degree head-down tilt (HDT), with primary outcomes being the predicted change in strains at the optic nerve head (ONH) region, specifically in the lamina cribrosa (LC), retrolaminar optic nerve, and prelaminar neural tissue (PLNT). The strain field can be decomposed into three orthogonal components, denoted as the first, second and third principal strains. We compare the peak tensile (first principal) and compressive (third principal) strains, since elevated strain alters cell phenotype and induces tissue remodeling. RESULTS AND CONCLUSIONS: Our lumped-parameter model predicted an IOP increase of c. 7 mmHg after 21 minutes of 15 degree HDT, which agreed with previous reports of IOP in HDT [1]. The corresponding FEM simulations predicted a relative increase in the magnitudes of the peak tensile and compressive strains in the lamina cribrosa of 42 and 43, respectively (Fig. 2). The corresponding changes in the optic nerve strains were 17 and 39, while in the PLNT they were 47 and 43. These magnitudes of relative elevations in peak strains may induce a phenotypic response in resident mechano-responsive resident cells [2]. This approach may be expanded to investigate other environmental changes (e.g. parabolic flight). Through our VIIP SCHOLAR project, we will validate and improve these integrated models by measuring patient-specific changes in optic nerve sheath geometry in patients with idiopathic intracranial hypertension before and after lumbar puncture and CSF removal.

biomechanics↗
NASA NTRS2016

Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology

The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.

biomechanics↗
NASA NTRS2016

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↗
NASA NTRS2016

Architecture for Integrated Medical Model Dynamic Probabilistic Risk Assessment

Probabilistic Risk Assessment (PRA) is a modeling tool used to predict potential outcomes of a complex system based on a statistical understanding of many initiating events. Utilizing a Monte Carlo method, thousands of instances of the model are considered and outcomes are collected. PRA is considered static, utilizing probabilities alone to calculate outcomes. Dynamic Probabilistic Risk Assessment (dPRA) is an advanced concept where modeling predicts the outcomes of a complex system based not only on the probabilities of many initiating events, but also on a progression of dependencies brought about by progressing down a time line. Events are placed in a single time line, adding each event to a queue, as managed by a planner. Progression down the time line is guided by rules, as managed by a scheduler. The recently developed Integrated Medical Model (IMM) summarizes astronaut health as governed by the probabilities of medical events and mitigation strategies. Managing the software architecture process provides a systematic means of creating, documenting, and communicating a software design early in the development process. The software architecture process begins with establishing requirements and the design is then derived from the requirements.

Probability Theory↗
NASA NTRS2016

Sensitivity Analysis of the Integrated Medical Model for ISS Programs

Sensitivity analysis estimates the relative contribution of the uncertainty in input values to the uncertainty of model outputs. Partial Rank Correlation Coefficient (PRCC) and Standardized Rank Regression Coefficient (SRRC) are methods of conducting sensitivity analysis on nonlinear simulation models like the Integrated Medical Model (IMM). The PRCC method estimates the sensitivity using partial correlation of the ranks of the generated input values to each generated output value. The partial part is so named because adjustments are made for the linear effects of all the other input values in the calculation of correlation between a particular input and each output. In SRRC, standardized regression-based coefficients measure the sensitivity of each input, adjusted for all the other inputs, on each output. Because the relative ranking of each of the inputs and outputs is used, as opposed to the values themselves, both methods accommodate the nonlinear relationship of the underlying model. As part of the IMM v4.0 validation study, simulations are available that predict 33 person-missions on ISS and 111 person-missions on STS. These simulated data predictions feed the sensitivity analysis procedures. The inputs to the sensitivity procedures include the number occurrences of each of the one hundred IMM medical conditions generated over the simulations and the associated IMM outputs: total quality time lost (QTL), number of evacuations (EVAC), and number of loss of crew lives (LOCL). The IMM team will report the results of using PRCC and SRRC on IMM v4.0 predictions of the ISS and STS missions created as part of the external validation study. Tornado plots will assist in the visualization of the condition-related input sensitivities to each of the main outcomes. The outcomes of this sensitivity analysis will drive review focus by identifying conditions where changes in uncertainty could drive changes in overall model output uncertainty. These efforts are an integral part of the overall verification, validation, and credibility review of IMM v4.0.

medical equipment↗
NASA NTRS2016

Integrated Medical Model (IMM) Optimization Version 4.0 Functional Improvements

The IMMs ability to assess mission outcome risk levels relative to available resources provides a unique capability to provide guidance on optimal operational medical kit and vehicle resources. Post-processing optimization allows IMM to optimize essential resources to improve a specific model outcome such as maximization of the Crew Health Index (CHI), or minimization of the probability of evacuation (EVAC) or the loss of crew life (LOCL). Mass and or volume constrain the optimized resource set. The IMMs probabilistic simulation uses input data on one hundred medical conditions to simulate medical events that may occur in spaceflight, the resources required to treat those events, and the resulting impact to the mission based on specific crew and mission characteristics. Because IMM version 4.0 provides for partial treatment for medical events, IMM Optimization 4.0 scores resources at the individual resource unit increment level as opposed to the full condition-specific treatment set level, as done in version 3.0. This allows the inclusion of as many resources as possible in the event that an entire set of resources called out for treatment cannot satisfy the constraints. IMM Optimization version 4.0 adds capabilities that increase efficiency by creating multiple resource sets based on differing constraints and priorities, CHI, EVAC, or LOCL. It also provides sets of resources that improve mission-related IMM v4.0 outputs with improved performance compared to the prior optimization. The new optimization represents much improved fidelity that will improve the utility of the IMM 4.0 for decision support.

risk assessment↗
NASA NTRS2016

Microgravity-Driven Optic Nerve/Sheath Biomechanics Simulations

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Current thinking suggests that the ocular changes observed in VIIP syndrome are related to cephalad fluid shifts resulting in altered fluid pressures [1]. In particular, we hypothesize that increased intracranial pressure (ICP) drives connective tissue remodeling of the posterior eye and optic nerve sheath (ONS). We describe here finite element (FE) modeling designed to understand how altered pressures, particularly altered ICP, affect the tissues of the posterior eye and optic nerve sheath (ONS) in VIIP. METHODS: Additional description of the modeling methodology is provided in the companion IWS abstract by Feola et al. In brief, a geometric model of the posterior eye and optic nerve, including the ONS, was created and the effects of fluid pressures on tissue deformations were simulated. We considered three ICP scenarios: an elevated ICP assumed to occur in chronic microgravity, and ICP in the upright and supine positions on earth. Within each scenario we used Latin hypercube sampling (LHS) to consider a range of ICPs, ONH tissue mechanical properties, intraocular pressures (IOPs) and mean arterial pressures (MAPs). The outcome measures were biomechanical strains in the lamina cribrosa, optic nerve and retina; here we focus on peak values of these strains, since elevated strain alters cell phenotype and induce tissue remodeling. In 3D, the strain field can be decomposed into three orthogonal components, denoted as first, second and third principal strains. RESULTS AND CONCLUSIONS: For baseline material properties, increasing ICP from 0 to 20 mmHg significantly changed strains within the posterior eye and ONS (Fig. 1), indicating that elevated ICP affects ocular tissue biomechanics. Notably, strains in the lamina cribrosa and retina became less extreme as ICP increased; however, within the optic nerve, the occurrence of such extreme strains greatly increased as ICP was elevated (Fig. 2). In particular, c. 48 of simulations in the elevated ICP condition showed peak strains in the optic nerve that exceeded the strains expected on earth. Such extreme strains are likely important, since they represent a larger signal for mechano-responsive resident cells [2]. The models predicted little to no anterior motion of the prelaminar neural tissue (optic nerve swelling, or papilledema, secondary to axoplasmic stasis), typically seen with elevated ICP. Specialized FE models to capture axoplasmic stasis would be required to study papilledema. These results suggest that the most notable effect of elevated ICP may occur via direct optic nerve loading, rather than through connective tissue deformation. These FE models can inform the design of future studies designed to bridge the gap between biomechanics and pathophysiological function in VIIP.

biomechanics↗
NASA NTRS2016

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↗
NASA NTRS2016

Qualitative Validation of the IMM Model for ISS and STS Programs

To validate and further improve the Integrated Medical Model (IMM), medical event data were obtained from 32 ISS and 122 STS person-missions. Using the crew characteristics from these observed missions, IMM v4.0 was used to forecast medical events and medical resource utilization. The IMM medical condition incidence values were compared to the actual observed medical event incidence values, and the IMM forecasted medical resource utilization was compared to actual observed medical resource utilization. Qualitative comparisons of these parameters were conducted for both the ISS and STS programs. The results of these analyses will provide validation of IMM v4.0 and reveal areas of the model requiring adjustments to improve the overall accuracy of IMM outputs. This validation effort should result in enhanced credibility of the IMM and improved confidence in the use of IMM as a decision support tool for human space flight.

risk assessment↗
NASA NTRS2016

Quantitative Validation of the Integrated Medical Model (IMM) for ISS Missions

Lifetime Surveillance of Astronaut Health (LSAH) provided observed medical event data on 33 ISS and 111 STS person-missions for use in further improving and validating the Integrated Medical Model (IMM). Using only the crew characteristics from these observed missions, the newest development version, IMM v4.0, will simulate these missions to predict medical events and outcomes. Comparing IMM predictions to the actual observed medical event counts will provide external validation and identify areas of possible improvement. In an effort to improve the power of detecting differences in this validation study, the total over each program ISS and STS will serve as the main quantitative comparison objective, specifically the following parameters: total medical events (TME), probability of loss of crew life (LOCL), and probability of evacuation (EVAC). Scatter plots of observed versus median predicted TMEs (with error bars reflecting the simulation intervals) will graphically display comparisons while linear regression will serve as the statistical test of agreement. Two scatter plots will be analyzed 1) where each point reflects a mission and 2) where each point reflects a condition-specific total number of occurrences. The coefficient of determination (R2) resulting from a linear regression with no intercept bias (intercept fixed at zero) will serve as an overall metric of agreement between IMM and the real world system (RWS). In an effort to identify as many possible discrepancies as possible for further inspection, the -level for all statistical tests comparing IMM predictions to observed data will be set to 0.1. This less stringent criterion, along with the multiple testing being conducted, should detect all perceived differences including many false positive signals resulting from random variation. The results of these analyses will reveal areas of the model requiring adjustment to improve overall IMM output, which will thereby provide better decision support for mission critical applications.

validation↗
NASA NTRS2015

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↗
NASA NTRS2015

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.↗
NASA NTRS2015

Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

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 in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

Bone Remodeling↗
NASA NTRS2015

Integrated Medical Model (IMM) 4.0 Enhanced Functionalities

The Integrated Medical Model is a probabilistic simulation model that uses input data on 100 medical conditions to simulate expected medical events, the resources required to treat, and the resulting impact to the mission for specific crew and mission characteristics. The newest development version of IMM, IMM v4.0, adds capabilities that remove some of the conservative assumptions that underlie the current operational version, IMM v3. While IMM v3 provides the framework to simulate whether a medical event occurred, IMMv4 also simulates when the event occurred during a mission timeline. This allows for more accurate estimation of mission time lost and resource utilization. In addition to the mission timeline, IMMv4.0 features two enhancements that address IMM v3 assumptions regarding medical event treatment. Medical events in IMMv3 are assigned the untreated outcome if any resource required to treat the event was unavailable. IMMv4 allows for partially treated outcomes that are proportional to the amount of required resources available, thus removing the dichotomous treatment assumption. An additional capability IMMv4 is to use an alternative medical resource when the primary resource assigned to the condition is depleted, more accurately reflecting the real-world system. The additional capabilities defining IMM v4.0the mission timeline, partial treatment, and alternate drug result in more realistic predicted mission outcomes. The primary model outcomes of IMM v4.0 for the ISS6 mission, including mission time lost, probability of evacuation, and probability of loss of crew life, are be compared to those produced by the current operational version of IMM to showcase enhanced prediction capabilities.

Spae Adaptation Syndrome↗