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Modeling the Effects of Spaceflight on the Posterior Eye in VIIP
C. R. ETHIER, A.J. FEOLA, J. RAYKIN, L. MULUGETA, R. GLEASON, J.G . MYERS, E.S. NELSON, AND B. SAMUELS
W W W. E T H I E R L A B . G AT E C H . E D U
https://ntrs.nasa.gov/search.jsp?R=20150011647 2018-05-24T18:25:30+00:00Z
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Slide 2
Commercial Relationships Disclosure
No relationships to disclose for any co-author
2
Funding support
o NASA Grant NNX13AP91G
o Georgia Research Alliance
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Slide 3
VIIP Syndrome Permanent changes in visual function/ocular anatomy after long-duration space flighto 41.7% incidence in U.S. astronauts
o Choroidal folds, papilledema, globe flattening, optic nerve dura distention/kinking
Kramer et al. Radiology, 2012.
Normal Astronaut with VIIP
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Slide 4
Hypothesis
Increased intracranial pressure (ICP) due to cephalad fluid shift
leads to:
o Connective tissue remodeling in the posterior eye/optic nerve sheath
o Mechanical loading/insult to ONH cells and tissues, and eventual vision loss
humanresearchroadmap.nasa.gov
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Slide 5
Goal
Study the biomechanical response of the optic nerve sheath and posterior eye to changes in ICP
o Account for different ICP “cases”o Terrestrial supine
o Terrestrial standing
o Microgravity (presumed elevated ICP)
o Account for variations of ICP within these cases
o Account for variations in tissue properties
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MethodsCOMPUTATIONAL (FINITE ELEMENT) MODEL
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Slide 7
ScleraRetinaPeripapillary
Sclera
DuraMater
PiaMater
CentralRetinalVessel
Axis of Rotation
OpticNerve
Lamina Cribrosa
Model Geometry
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Slide 8
Name Abbreviation Units BaselineStandard Deviation
Low High
Pressures
Intraocular Pressure IOP mmHg 15 1.85 10 19
Intracranial Pressure ICP mmHg
Upright 0 2.0 -4 4
Supine 10 2.0 6 14
Elevated 20 2.5 15 25
Mean Arterial Pressure MAP mmHg 86 7.96 60 112
Biomechanical Properties
Sclera Young’s modulus SC MPa 5 1 9
Peripapillary Sclera Young’s modulus ppSC MPa 5 1 9
Lamina Cribrosa Young’s modulus LC MPa 0.5 0.1 0.9
Pia Mater Young’s modulus Pia MPa 5 1 9
Dura Mater Young’s modulus Dura MPa 1 0.2 2
Optic Nerve Young’s modulus ON MPa 0.05 0.01 0.09
Retina Young’s modulus Ret MPa 0.05 0.01 0.09
Retinal Vessel Young’s modulus RV MPa 0.3 0.2 0.4
Neural Poisson’s ratio Poisson’s - 0.45 0.4 0.49
Model Inputs
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Slide 9
Latin hypercube samplingEfficiently simulates variation in input parameters (Monte Carlo)
Intracranial Pressure (mmHg)
Mean Arterial Pressure (mmHg)
Intraocular Pressure (mmHg)
12 14 16 18
60 80 100
-5 5 15 25
Upright Supine Elevated
0 5 10ONH Material Properties(SC, ppSC, LC, Pia, Dura, ON,
Ret, RV and Poisson’s)
Upright Supine Elevated
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Slide 10
Outcome measure
Strain in ONH tissueso Physical quantity that represents stretching of
cells and tissues
o Local cells are mechanoresponsive
o Strain drives connective tissue remodeling in many other tissues, e.g. artery walls
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ResultsCOMPUTATIONAL (FINITE ELEMENT) MODEL
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Slide 12
ICP: 0 mmHg ICP: 10 mmHg ICP: 20 mmHg
1st Principal Strain
(Stretch)
3rd Principal Strain
(Compression)
2.0%
-2.0%
Effect of ICP: Baseline case
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Slide 13
Average strains: Baseline case
Tissue Region: Lamina Cribrosa Optic Nerve Retina
Strain Type: Tension Compression Tension Compression Tension Compression
ICP = 0 mmHg 0.57% -0.86% 0.61% -0.85% 0.35% -0.48%
ICP = 10 mmHg 0.78% -1.11% 0.78% -1.21% 0.63% -0.83%
ICP = 20 mmHg 0.97% -1.35% 0.96% -1.56% 0.91% -1.21%
Regions of Interest: Retina
Lamina Cribrosa
Optic Nerve
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Slide 14
Lamina Cribrosa Strain Histograms
TensionCompression
0
300
600
900
-1.00% -0.50% 0.00% 0.50% 1.00%
Pro
bab
ility
Den
sity
Est
imat
e
Strain
1st Principal Strain3rd Principal Strain
5th Percentile
95th Percentile
Denote 5th and 95th
percentile values as “Peak strains”
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Slide 15
Distribution within population
0% 5%1% 2% 3% 4%
Use Latin Hypercube Sampling
Peak strain in LC
Histogram
Cumulative Distribution
100%
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Slide 16
0
0.2
0.4
0.6
0.8
1
-4% -2% 0% 2% 4%
Cu
mu
lati
ve P
rob
abili
tyUpright ICPSupine ICPElevated ICP
“Peak” Strains in Lamina Cribrosa
TensionCompression
0
0.2
0.4
0.6
0.8
1
-4% -2% 0% 2% 4%
Cu
mu
lati
ve P
rob
abili
ty
0
0.2
0.4
0.6
0.8
1
-4% -2% 0% 2% 4%
Cu
mu
lati
ve P
rob
abili
ty
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Slide 17
0
0.2
0.4
0.6
0.8
1
-4% -2% 0% 2% 4%
Cu
mu
lati
ve P
rob
abili
tyUpright ICPSupine ICPElevated ICP
“Peak” Strains in Retina
TensionCompression
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Slide 18
0
0.2
0.4
0.6
0.8
1
-4% -2% 0% 2% 4%
Cu
mu
lati
ve P
rob
abili
tyUpright ICPSupine ICPElevated ICP
“Peak” Strains in Optic Nerve
5%
20%
TensionCompression
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Slide 19
“Out of this World Strains”
Tissue Region: Lamina Cribrosa Optic Nerve Retina
Strain Type: Tension Compression Tension Compression Tension Compression
Supine 8% 5% 20% 6% 10% 13%
Percentage of individuals with elevated ICP experiencing strains larger than those experienced under terrestrial conditions (standing or supine)
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Optic Nerve SheathEXPERIMENTAL MEASUREMENTS
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Slide 21
Collagen orientation in duraSHG microscopy images of dura
0 mm Hg 10 mm Hg
Nerve Axis Nerve Axis
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Slide 22
Optic nerve has slack
Liu et al., BJO, 1992
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Slide 23
What is state of ON stretch?
Perform craniotomy
Expose orbit
Remove periorbital tissue
covering the optic nerve
Place markers on the optic
nerve
Transect nerve and record
axial retraction
Expose optic nerve, transect, observe retraction (or not)
http://www.dcfirst.com/pig_anatomy_poster.html
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Slide 24
Optic nerve retraction
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Slide 25
Summary
ICP affects strains in ONH tissues:◦ Average strain values are low
◦ Simulation of “population” shows that 5-20% of individuals will experience ICP-induced strains in space that are more extreme than those on earth
Uncertainties/Limitations◦ Optic nerve appears to be under tension (?!)
◦ Some tissue properties still not well understood
◦ Pathophysiology of vision loss and connection with strain not established
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Slide 26
BME at Georgia Tech/Emory