laboratory of biological structure mechanics compressive properties of intraluminal thrombus from...
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LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS
www.labsmech.polimi.it
Compressive properties of intraluminal thrombus from abdominal aortic aneurysms
Federica Boschetti
Introduction
Abdominal aortic aneurysm (AAA) is the15th leading cause of death in the U.S. (Al-Omran et al., 2004, NCFH, 2000)
Unless treated, rupture of AAA is associated with an emergency postoperative mortality rate of 47% (Resch et al., 2001)
Current method for determining risk of rupture is not reliable (Darling et al., 1977, Lederle et al., 2002)
The presence of an ILT is a common finding in AAAs and may potentially play an important, though as yet unknown, role in the progression of the disease (Vorp, 1997).
5.5 cm5.5 cm
Measurement of MMPs
lost of elastin early aortic expansion
collagen breakdown late expansion and rupture Dobrin et al, 1984
Biological approach
MMP-2 and MMP-9 are specific to elastase
MMP-1 and MMP-8 are specific to collagenase
MMPs are endogenous proteases implicated in aneurysm pathobiology
MMP-8 and MMP-9 are increased at the site of AAA rupture (Wilson et al, 2006)
Biomechanical approach
Strength
Stress(RPI)Index Potential Rupture
AAA rupture is an event marked by catastrophic mechanical failure of the diseased aortic wall tissue
Mechanical failure of a material occurs when the acting stress exceeds the material’s strength
Predictive realistic model: geometry + material properties (AAA+ILT) + physiologic loads
stress strength
Numerical model
Statistical model (thickness,curvature,family hystory, age, sex)
Biomechanical approach
(IDL)
CT Image Segmentation
3D Smoothing
IGES Splines
CAD model
Mesh discretisation
FEM simulation
Biomechanical approach
(IDL)
CT Image Segmentation
A BA B
AAA lumen ILT
Intervertebral disc
AAA lumen ILT
Intervertebral disc
3D Smoothing
IGES Splines
CAD model
Mesh discretisation
FEM simulation
Biomechanical approach
(IDL)
CT Image Segmentation
3D Smoothing
Mesh discretisation
FEM simulation
A B CA B C
A B CA B C
IGES Splines
CAD model
Biomechanical approach
(IDL)
CT Image Segmentation
3D Smoothing
IGES Splines
CAD model
Mesh discretisation
FEM simulation
Biomechanical approach
(IDL)
CT Image Segmentation
3D Smoothing
IGES Splines
CAD model
Mesh discretisation
FEM simulation
strength AAA wall
stress AAA wallRPI
Material properties ??
FEM model
• Structural model
• Fluid-dynamic model
• Fluid-structure interaction model
Material properties - Experimental tests
Experimental set-up
AAA specimen
E.S. Di Martino J Vasc Surg. 2006 Mar;43(3):570-6
Uniaxial tensile tests on AAA wall
Wang et al., 2002, Di Martino, 2003
Material properties - Experimental tests
L
Biaxial tensile tests on AAA wall
Material properties - Experimental tests
Biaxial tensile tests on ILT
Luminal layer isolated (2mm ave thickness) Tested biaxially
Wang et al., 2002, Di Martino, 2003
Compressive properties are missing
Aim: to evaluate the mechanical properties of ILT under compressive loads
ILT from O.R. cylindrical plugs liquid N2
on the day of testing: 3 slices from each plug (luminal, medial, abluminal)
all mechanical tests performed in a bath of physiologic solution
Material properties - Experimental tests
Compression tests on ILT
R.Spirito, Centro Cardiologico Monzino, Milano
Elastic Modulus E (from uc stress-relaxation)
Aggregate Modulus Ha (from cc stress-relaxation)
Permeability K (from permeation - Darcy)
Porosity (from wet to dry weight)
Methods: Material properties - Experimental tests
Compression tests on ILT – choice of the constitutive model
Measured parameters
ILT soft hydrated tissue (fibrin, cells, 90% water) biphasic theory
Solid phase
Isotropic
Elastic
Uncompressible
Fluid phase
Inviscid
Uncompressible
K,
Compression tests on ILT – stress-strain data
Methods: Material properties - Experimental tests
Testing machine: Enduratec Elf 3200, 22N load cell
v = 0.1m/s
Stress-Strain
0
100
200
300
400
500
600
700
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5 0.55 0.6 0.65 0.7 0.75 0.8
strain
mm
Hg
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
MP
a
luminalmedialabluminal
0
)(
E
step wise stress relaxation test
Strain=40%-45%-50%-55%
stepwise unconfined compression
-0.5
-0.4
-0.3
-0.2
-0.1
0
0 5000 10000 15000 20000 25000 30000 35000
time (s)
forc
e (N
)
Compression tests on ILT: unconfined compression
Methods: Material properties - Experimental tests
ΔU
radial flow
axial flow
Compression tests on ILT: confined compression
0
)(
Ha
step wise stress relaxation test
Strain=40%-45%-50%-55%
stepwise unconfined compression
-0.5
-0.4
-0.3
-0.2
-0.1
0
0 5000 10000 15000 20000 25000 30000 35000
time (s)
forc
e (N
)
Methods: Material properties - Experimental tests
Measurement of the volume flow
through thrombus
Application of a constant load to
the fluid
Measurement of the resulting
pressure
hka Pj
P
h
P
h
Darcy law
Permeation tests on ILT
Methods: Material properties - Experimental tests
Biochemical analysis
Homogenization in 0.05 mol/L Tris-HCl, pH 7.6, containing proteases inhibitors.
Centrifugation at 16000 rpm for 15 minutes at 4°C MMP-9 levels assessed by Elisa assay (Quantikine MMP9, R&D system)
Methods: Biochemical analysis
M.Camera and R.Ballerio, Centro Cardiologico Monzino, Milano
Results
Aggregate Modulus
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
0.45 0.50 0.55
strain
KP
a
luminal
medial
abluminal
0
20
40
60
80
100
120
luminal medial abluminal
MM
P9
(n
g/m
g p
rote
in)
0
200
400
600
800
1000
luminal medial abluminal
MM
P9
(% o
ver
ablu
min
alco
nte
nt)
Permeability
0
2E-14
4E-14
6E-14
8E-14
1E-13
1.2E-13
luminal medial abluminal
m4/
N-s
luminal
medial
abluminal
data from 3 patients
Elastic Modulus
0.0010.0020.0030.0040.0050.0060.0070.0080.0090.00
0.45 0.50 0.55
strain
E (
KP
a)
luminal
medial
abluminal
Conclusions
ILT is a non-homogeneous material: the compression and biochemical properties vary widely across the thickness
Stratification of the material properties may be related to ILT formation, which
occur in time by successive layers.
Work in progress and future developments:
more tests
comparison between ruptured and non ruptured
search for correlations
fluid-structure interaction
remodeling law implementation
pressure gaugepressure gauge
capillarycapillary
PE filterPE filter
samplesample O-RingO-Ring
lower lower cylindercylinder
upper upper cylindercylinder
Permeation tests on ILT
Methods: Material properties - Experimental tests