The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report

Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of changes in bone cell populations that remove and replace bone in packets within the bone region. The DAP bone model is unique in several respects. In particular in takes former models of volume fraction changes one step higher in fidelity and separates BVF into separate equations for mineralized and osteoid volume fractions governed by a mineralization rate. This more closely follows the physiology of the remodeling unit cycles where bone is first resorbed and then followed by the action of osteoblasts to lay down collagen matrix which eventually becomes mineralized. In another respect, the modules allow the functional description of the time rate of change of other parameters and variables in the model during a computational simulation. More detailed description of the model, preliminary validation results, current limitation and caveats, and planned advancements are provided in sections 2 through 5. The DAP bone model is being developed primarily as a research tool, and not as a clinical tool like QCT. Even if it transitions to a clinical tool, it is not intended to replace QCT or any other clinical tool. Moreover, the DAP bone model does not predict bone fracture. Its purpose is to provide valuable additional data via "forward prediction" simulations for during and after spaceflight missions to gain insight on, (1) mechanisms of bone demineralization in microgravity, and (2) the volumetric changes at the various bone sites in response to in-flight and post-flight exercise countermeasures. This data can then be used as input to the Keyak [8] (or equivalent) FE analysis method to gain insight on how bone strength may change during and after flight. This information can also be useful to help optimize exercise countermeasure protocols to minimize changes in bone strength during flight, and improve regain of bone strength post-flight. To achieve this goal, the bone model will be integrated with DAP's exercise countermeasure models to simulate the effect of exercise prescriptions on preserving bone. More specifically, the model will accept loading history due to muscle and joint force on bone and produce quantified remodeling within the bone region under influence of the applied stress. Furthermore, because they tend to respond differently, the bone remodeling model includes both trabecular bone and cortical bone

Evaluating Daily Load Stimulus Formulas in Relating Bone Response to Exercise

Six formulas representing what is commonly referred to as "daily load stimulus" are identified, compared and tested in their ability to relate skeletal mechanical loading to bone maintenance and osteogenic response. Particular emphasis is placed on exercise- induced skeletal loading and whether or not the formulas can adequately capture the known experimental observations of saturation of continuous cyclic loading, rest insertion between repetitions (cycles), recovery of osteogenic potential following saturation, and multiple shorter bouts versus a single long bout of exercise. To evaluate the ability of the formulas to capture these characteristics, a set of exercise scenarios with type of exercise bout, specific duration, number of repetitions, and rest insertion between repetitions is defined. The daily load values obtained from the formulas for the loading conditions of the set of scenarios is illustrated. Not all of the formulas form estimates of daily load in units of stress or in terms of strain at a skeletal site due to the loading force from a specific exercise prescription. The comparative results show that none of the formulas are able to capture all of the experimentally observed characteristics of cyclic loading. However, the enhanced formula presented by Genc et al. does capture several characteristics of cyclic loading that the others do not, namely recovery of osteogenic potential and saturation. This could be a basis for further development of mathematical formulas that more adequately approximates the amount of daily stress at a skeletal site that contributes to bone adaptation

A Computational Model for Simulating Spaceflight Induced Bone Remodeling

An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model

Mapping Bone Mineral Density Obtained by Quantitative Computed Tomography to Bone Volume Fraction

Methods for relating or mapping estimates of volumetric Bone Mineral Density (vBMD) obtained by Quantitative Computed Tomography to Bone Volume Fraction (BVF) are outlined mathematically. The methods are based on definitions of bone properties, cited experimental studies and regression relations derived from them for trabecular bone in the proximal femur. Using an experimental range of values in the intertrochanteric region obtained from male and female human subjects, age 18 to 49, the BVF values calculated from four different methods were compared to the experimental average and numerical range. The BVF values computed from the conversion method used data from two sources. One source provided pre bed rest vBMD values in the intertrochanteric region from 24 bed rest subject who participated in a 70 day study. Another source contained preflight vBMD values from 18 astronauts who spent 4 to 6 months on the ISS. To aid the use of a mapping from BMD to BVF, the discussion includes how to formulate them for purpose of computational modeling. An application of the conversions would be used to aid in modeling of time varying changes in vBMD as it relates to changes in BVF via bone remodeling and/or modeling

Ethiopia’s response to climate change and gender

The Ministry of Finance Climate Resilient Green Economy Facility invited the Climate and Development Knowledge Network (CDKN) to conduct an assessment of the integration of gender considerations into planning, budgeting, monitoring and evaluation (M&E) and project execution. Consultations focused on two lead federal organizations responsible for coordinating climate change actions in Ethiopia: the Environment, Forest and Climate Change Commission (EFCCC), and the Ministry of Finance (MoF). The study focused on gender-responsive budgeting in the implementation of climate change policy. To assess the status of gender mainstreaming within various departments in the EFCCC and MoF, interviews were held with key informants.Ministry of Foreign Affairs of the Netherland

Computational Models of the Eye and their Applications in Long Duration Space Flight

Astronauts are exposed to cephalad fluid shift, increased carbon dioxide levels and other environmental factors during space flight. As a result of these conditions, it is believed that they are at risk of developing increased intracranial pressure (ICP) and intraocular pressure (IOP), which in turn may cause papilledema and other disorders of the eye that can lead to temporary or permanent changes in vision. However, the mechanisms behind this risk are not fully understood. Ground analog and flight studies pose challenges because there are limited non-invasive methods that can be used to study the eye and intracranial space. Therefore it is proposed that computational models can be applied to help address this gap by providing a low cost method for studying the effects of IOP, ICP and various properties of the eye on these diseases. The information presented by the authors provides a summary of several models found in literature that could potentially be augmented and applied to inform research. Specifically, finite element models of the optic nerve head, sclera and other structures of the eye can be readily adapted as potential building blocks. These models may also be integrated with a brain/cerebrospinal fluid (CSF) model which will take into account the interaction between the CSF fluid and its pressure on the optic nerve. This integration can enable the study of the effects of microgravity on the interaction between the vasculature system and CSF system and can determine the effects of these changes on the optic nerve, and in turn the eye. Ultimately, it can help pinpoint the influences of long-term exposure to microgravity on vision and inform the future research into countermeasure development. In addition to spaceflight, these models can provide deeper understanding of the mechanisms of glaucoma, papilledema and other eye disorders observed in terrestrial conditions

Can We Trust Computational Modeling for Medical Applications?

Operations in extreme environments such as spaceflight pose human health risks that are currently not well understood and potentially unanticipated. In addition, there are limited clinical and research data to inform development and implementation of therapeutics for these unique health risks. In this light, NASA's Human Research Program (HRP) is leveraging biomedical computational models and simulations (M&S) to help inform, predict, assess and mitigate spaceflight health and performance risks, and enhance countermeasure development. To ensure that these M&S can be applied with confidence to the space environment, it is imperative to incorporate a rigorous verification, validation and credibility assessment (VV&C) processes to ensure that the computational tools are sufficiently reliable to answer questions within their intended use domain. In this presentation, we will discuss how NASA's Integrated Medical Model (IMM) and Digital Astronaut Project (DAP) have successfully adapted NASA's Standard for Models and Simulations, NASA-STD-7009 (7009) to achieve this goal. These VV&C methods are also being leveraged by organization such as the Food and Drug Administration (FDA), National Institute of Health (NIH) and the American Society of Mechanical Engineers (ASME) to establish new M&S VV&C standards and guidelines for healthcare applications. Similarly, we hope to provide some insight to the greater aerospace medicine community on how to develop and implement M&S with sufficient confidence to augment medical research and operations

Modeling and Simulation of Visual Impairment and Intracranial Pressure (VIIP) in Space

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Models of the Eye: Relevance to Microgravity Induced Visual Impairment and Intracranial Pressure

No abstract availabl

Credibility Assessment of Deterministic Computational Models and Simulations for Space Biomedical Research and Operations

Human missions beyond low earth orbit to destinations, such as to Mars and asteroids will expose astronauts to novel operational conditions that may pose health risks that are currently not well understood and perhaps unanticipated. In addition, there are limited clinical and research data to inform development and implementation of health risk countermeasures for these missions. Consequently, NASA's Digital Astronaut Project (DAP) is working to develop and implement computational models and simulations (M&S) to help predict and assess spaceflight health and performance risks, and enhance countermeasure development. In order to effectively accomplish these goals, the DAP evaluates its models and simulations via a rigorous verification, validation and credibility assessment process to ensure that the computational tools are sufficiently reliable to both inform research intended to mitigate potential risk as well as guide countermeasure development. In doing so, DAP works closely with end-users, such as space life science researchers, to establish appropriate M&S credibility thresholds. We will present and demonstrate the process the DAP uses to vet computational M&S for space biomedical analysis using real M&S examples. We will also provide recommendations on how the larger space biomedical community can employ these concepts to enhance the credibility of their M&S codes