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Gleason, R.

Publications and source records attributed to Gleason, R..

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.↗

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↗

Finite Element Modeling Techniques for Analysis of VIIP

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.

eye (anatomy)↗

Numerical Modeling of Ocular Dysfunction in Space

Upon introduction to microgravity, the near-loss of hydrostatic pressure causes a marked cephalic (headward) shift of fluid in an astronaut's body. The fluid shift, along with other factors of spaceflight, induces a cascade of interdependent physiological responses which occur at varying time scales. Long-duration missions carry an increased risk for the development of the 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. In the cases of VIIP found to date, the initial onset of symptoms occurred after several weeks to several months of spaceflight, by which time the gross bodily fluid distribution is well established. We are developing a suite of numerical models to simulate the effects of fluid shift on the cardiovascular, central nervous and ocular systems. These models calculate the modified mean volumes, flow rates and pressures that are characteristic of the altered quasi-homeostatic state in microgravity, including intracranial and intraocular pressures. The results of the lumped models provide initial and boundary data to a 3D finite element biomechanics simulation of the globe, optic nerve head and retrobulbar subarachnoid space. The integrated set of models will be used to investigate the evolution of the biomechanical stress state in the ocular tissues due to long-term exposure to microgravity.

intraocular pressure↗

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↗