Computational Modeling and Simulation of Microgravity Induced Visual Impairment and

Intracranial Pressure (VIIP)

HRP Investigators’ Workshop Galveston, TX

February 13, 2013

Lealem Mulugeta1, Lauren Best2, Jerry G. Myers2 and E.S. Nelson2 1Universities Space Research Association, Houston, Texas

2NASA Glenn Research Center, Cleveland, OH

Focus Area for Modeling and Simulation of VIIP

HRP IWS - Galveston, TX - February 13, 2013

Changes in visual acuity

Intraocular Pressure

(Adapted from Google Body – http://bodybrowser.googlelabs.com)

Optic disc edema

Intracranial Hemodynamics

Intracranial Pressure

Cerebrospinal Fluid Flow

Intracranial Compliance

Cardiovascular System

Guiding Knowledge Gap Questions VIIP1: What is the etiology of visual acuity and ocular structural and functional changes seen in-flight and postflight? CV7: How are fluids redistributed in flight?

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M&S Approach • Integration of lumped-parameter

models for whole body and eye to study ICP and IOP in mg

• Detailed model of the eye and surrounding tissues to investigate biomechanical stress and anatomical changes due to long-term mg exposure

Potential Causal Factors in VIIP

The causal chain linking microgravity and VIIP is at present unknown, but key factors DAP will consider include:

• Cephalad fluid shift

• Hydrodynamic forces governed by ICP and blood/CSF flow in the intracranial space

• Quasi-static and dynamic biomechanical responses of the corneo-retino-scleral shell, the optic nerve head (ONH) and its surrounding tissues to changes in ICP, IOP and fluid flow; and

• Tissue properties such as scleral deformation and remodeling characteristics

CEPHALAD FLUID SHIFT

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Overarching Modeling Approach

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NOTE: The above modeling tasks will be coordinated to complement NRA award tasks on “Computational Models of Cephalad Fluid Shifts”

Eye FEM (FY14+)

Ophthalmic changes

Lumped-Parameter (LP) of

CVS, CNS, LS & eye

(FY13+)

CFD/FSI model of Intracranial and Spinal

System (CNS) (Timeline TBD)

CSF and vascular Pressure

CSF and vascular pressure

Non-linear/ viscoelastic & collagen fibril behavior

High fidelity tissue model

(FY13+) Non-linear/ viscoelastic and collagen fibril behavior

Chronic simulations and parametric studies

Tissue compliance sensitivity analysis

Lumped-Parameter (LP) Modeling to Capture Cephalad Fluid Shift

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• Lumped-parameter (LP) whole-body and eye models for time-dependent pressure/flow of blood and CSF in CVS, CNS, the eye and subarachnoid space (SAS) posterior to the eye – Mean ICP and IOP after fluid redistribution has stabilized in space – Heartbeat-dependent fluctuations for peak ICP after fluid redistribution, as well

as during exercise and valsalva maneuver

• LP models drive spatially resolved models for detailed analysis of ocular biomechanics and anatomical changes

LP representation of fluid distribution in 1g and mg Relationship among LP and spatially resolved models

See poster #1084 by Nelson et al., “Computational Modeling of Cephalad Fluid Shift for Application to Microgravity-Induced Visual Impairment” for details.

Sources of inspiration for LP Modeling

• Hybrid model will be developed progressively by adapting methods from – Heldt, Lakin and Stevens: CVS and CNS

systems modeling for spaceflight conditions

– Lakin and Stevens: blood-brain barrier and heritage for microgravity ICP prediction simulations

– Linninger: higher fidelity representation of the flow dynamics and brain tissue properties, and representation of very small compartments

– Kiel et al.: LP model of globe, choroid, and aqueous humor dynamics, with translaminar pressure gradient and blood/aqueous flows

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(Lakin et al., 2007)

Linninger et al. (2009)

Spatially Resolved Modeling of the Eye and Retrobulbar SAS (RB-SAS)

• Include corneo/scleral shell, choroid layer and retina, ONH, and RB-SAS • Coupled with LP or CFD/FSI model to investigate fluid/structure interaction driven by

applied pressure at base of RB-SAS • High fidelity tissue modeling algorithm to investigate non-linear/viscoelastic and

collagen fibril response (e.g. possible scleral remodeling) • Minimal experimental or M&S research regarding the RB-SAS

RB-SAS

ON ON ON

- Killer et al. (2003)

Trabeculae (small beams/pillars)

OPTIC NERVE

Septae (sheets) and pillars

OPTIC NERVE

DURA

Norman et al. (2011) Furlani et al. (2012) 7

Sigal et al. (2004) Sigal & Ethier (2009)

CFD/FSI Modeling of the Spinal and Intracranial Compartments

Sweetman et al. (2011)

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CFD/FSI (spatially resolved) modeling methods can be useful for detailed investigations of the intracranial and spinal compartments answer questions relating to: • CSF and vascular flow dynamics • Mechanisms of dynamic and adaptive

response of anatomical structures Scope and questions have to be well defined to ensure for meaningful and high impact outcomes LP models will be used for hypothesis testing and generating appropriate boundary conditions to establish CFD/FSI simulations to answer well defined questions

Sweetman & Linninger (2010) (Vaičaitis et al. 2011)

Timeline TBD

Verification and Validation

• All models and simulations (M&S) will be verified and validated in accordance to NASA-STD-7009

• Obtain data from LSAH/LSDA to develop and validate M&S

• Establish collaborative data sharing agreement with current and future NASA and NSBRI funded VIIP investigators

• Work closely with VIIP Project Scientist and subject matter experts for technical review of M&S

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What we could do with the models

FE model of globe/

choroid/RB-SAS

Tissue remodeling algorithm

Integrated LP model of

CVS/CNS/LS

LP model of globe/choroid/ aqueous space

• Mean ICP after weeks in mg • Peak ICP during

exercise/valsalva in mg

• Visual acuity change • Ocular hypotony/hypertony • Reversible ONS distension,

globe deformation • Biomechanical effects of

venous congestion, choroidal engorgement

• IOP as a function of ICP, blood/aqueous humor flow

• Effect of venous congestion on IOP

• Persistent anatomical changes (globe flattening, ONS distension)

• Effect of mission duration 10

Questions