A significant number of astronauts who have participated in long-duration spaceflight missions (~6 months) aboard the International Space Station have returned with permanent changes in their visual acuity. Space medicine experts have suggested that the large displacement of body fluid toward the head caused by microgravity exposure may be partly responsible for these changes via biomechanical pathways. The DAP is developing computational simulations to inform research by testing potential pathways by which gravitational unloading could cause changes to the structure of the eye. Identifying critical parameters and features along the causal chain of biomechanical response can then be used to guide therapeutics development.

1. 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

2. 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?
2
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

3. 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
HRP IWS - Galveston, TX - February 13, 2013 3

4. Overarching Modeling Approach
4
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

5. Lumped-Parameter (LP) Modeling to
Capture Cephalad Fluid Shift
5
• 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.

6. 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
HRP IWS - Galveston, TX - February 13, 2013 6
(Lakin et al., 2007)
Linninger et al. (2009)

7. 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)

8. CFD/FSI Modeling of the Spinal and
Intracranial Compartments
Sweetman et al. (2011)
8
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

9. 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
HRP IWS - Galveston, TX - February 13, 2013 9

10. 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

11. Questions