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LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS www.labsmech.polimi.it Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica Boschetti

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Page 1: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS

www.labsmech.polimi.it

Compressive properties of intraluminal thrombus from abdominal aortic aneurysms

Federica Boschetti

Page 2: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 3: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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)

Page 4: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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)

Page 5: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

Biomechanical approach

(IDL)

CT Image Segmentation

3D Smoothing

IGES Splines

CAD model

Mesh discretisation

FEM simulation

Page 6: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 7: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 8: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

Biomechanical approach

(IDL)

CT Image Segmentation

3D Smoothing

IGES Splines

CAD model

Mesh discretisation

FEM simulation

Page 9: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 10: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 11: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

Wang et al., 2002, Di Martino, 2003

Material properties - Experimental tests

L

Biaxial tensile tests on AAA wall

Page 12: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 13: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 14: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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,

Page 15: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 16: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 17: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 18: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 19: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 20: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 21: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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

Page 22: LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS  Compressive properties of intraluminal thrombus from abdominal aortic aneurysms Federica

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