Truestress (MPa)

(1)

Centre for Centre for Centre for

Centre for Health Health Health Health Engineering Engineering Engineering Engineering CNRS UMR 5146

St St

St Sté é é éphane Avril and coll. phane Avril and coll. phane Avril and coll. phane Avril and coll.

Mechanics of the wall of blood vessels:

computational and experimental approaches

(2)

Lille - 2011/11/22 - LML - Stéphane AVRIL

INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION

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3

The center for Health Engineering

Improving health through science and engineering.

New campus in 2013

(4)

4 laboratories

FROM FUNDAMENTAL RESEARCH TO APPLICATIONS

Chemistry, kinetics, Thermodynamics Physics of solids Mechanics

Applied mathematics Operational research, Statistic

Computer science

Rhumatology Orthopedics,

Oto-rhino –larygology Cardiovascular Phlébology Opthalmology Immunology

Logistics of health care structures

Biomechanics and Biomaterials

Image processing

Health care engineering

Toxicity of inhalated nanoparticles

50 staff in Feb. 2011:

16 faculty + 4 tech , 27 PhD students, 3 Post Docs

Research activities

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5

CNRS UMR 5146

Scientific environment

Equipex IVTV

(6)

Biomechanics and Biomaterials

- Bio-tribo-corrosion of hip prosthesis

- Synthesis and characterization of bone scaffolds

- Mechanics of soft tissues

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7

Motivations

V V V Vascular ascular ascular ascular disorders disorders disorders disorders

Atherosclerotic plaque

Hypertension

Vascular reconstruction

……

THE WALL MECHANICS IS ESSENTIAL THE WALL MECHANICS IS ESSENTIAL THE WALL MECHANICS IS ESSENTIAL THE WALL MECHANICS IS ESSENTIAL

Aneurysms

(8)

COMPUTATIONAL WORK ON ATHEROMATOUS COMPUTATIONAL WORK ON ATHEROMATOUS COMPUTATIONAL WORK ON ATHEROMATOUS COMPUTATIONAL WORK ON ATHEROMATOUS PLAQUES

PLAQUES

(9)

9

1.1/Medical problem

Stroke Carotid bifurcation

Thrombo-embolic events from a carotid plaque rupture is the main cause of strokes

Atheromatous plaque

Plaque fracture

2/ 23

(10)

1.2/Plaque localisation

Plaque in internal carotid Plaque in carotid bifurcation

Plaque

Plaque often short or/and

irregular

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11

1.2/Plaque morphology

Transversal slide of plaque

Type IV,V: atheroma with a confluent extracellular lipid core fibroatheroma

Type VI: complex plaque with possible surface defect, hemorrhage, or thrombus

Possible vulnerable plaque *

Healthy artery wall

Arterial lumen

Fibrous cap

Lipid core

* Cai et al., 2002. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 2006: 1368-1373.

4/ 23

(12)

1.3/Current clinical actions

Treatment of vulnerable plaque is necessary to prevent stroke

Diagnosis of the plaque vulnerability

Luminography Carotid endarterectomy

NASCET, ECST:

S<70%

Research of other criteria could improve the diagnosis of But only the endoluminal stenosis do not reflect

the plaque vulnerability

S

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13

Layout

• Biomechanical approach

• Plaque characteristics

• Computational model

• Results

• Conclusion

Research of other criteria could improve the diagnosis of the plaque vulnerability

6/ 23

(14)

2/Biomechanical approach

Influence of the plaque properties on

the plaque vulnerability ?

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15

2/Biomechanical approach

Virtual histology using Resonance Magnetic Imaging *

* Cai et al., 2002. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 1006: 1368-1373.

Plaque (type VI)

Plaque morphology, constitution and mechanical properties

Plaque vulnerability

8/ 23

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3/Plaque characteristics

Lipid core Fibrous cap

Healthy artery wall (media+adventice)

Plaque components

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17

3/Plaque characteristics

Stenosis severity and plaque length

Plaque length L

Stenosis severity S

• 5mm<L<20mm

No vulnerable plaque according to NASCET and ECST

• 20%<S<70%

D

0

_D

0

1 D

S = − D

1/ Medical context 1.1/Medical problem 1.2/Plaque localisation 1.2/Plaque morphology 1.3/Current clinical actions

Layout

2/Biomechanical approach

3/Plaque characteristics

4/Computational model

5/Results

5.1/Compression vs shear

5.2/Pinching effect 5.3/Experimental study 5.4/Experimental and numerical comparaison

5.5/More complex geometry

6/Conclusion

10/ 23

(18)

3/Plaque characteristics

Asymmetry

H1 H2

If

1 2

H As = H

axisymmetry

“totale” asymmetry

2

1

H

H =

2

= 0

If H

then As = 1

then As = 0

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19

4/Computational model

Development of

computational model mimicking real plaques

2D Axisymmetric model

Fluid-structure interaction is resolved using the commercial codes COMSOL

fluid structure

12/ 23

(20)

4/Computational model

Development of

computational model mimicking real plaques

Fluid-structure interaction is resolved using the commercial codes ANSYS

3D model

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21

4/Computational model

) , ( t r

v _f ^p ^{( t} ^r ^, ⁾

Fluid incompressible viscous



 



=

/

3

1050

. 005 . 0

m kg

s Pa

f f

ρ η

) , ( t r

v _f _p _{( t} _r _, ₎

14/ 23

(22)

4/Computational model

Structure components: incompressible non linear hyperelastic anisotropic (Holzapfel model)

2 6

, 4

) 1 ( 2

1 1

6 4

1

( 1 )

) 2 1 2 (

) 3 2 (

) , , ,

( = − + ∑

² ²

− + −

=

−

J

k e I k

J c I I I

i

I

k _i

κ

ϕ

Components ComponentsComponents

Components ((((kPakPakPakPa)))) ((((kPakPakPa))))kPa ((((----)))) ((((°)))) Fibrous cap

Fibrous capFibrous cap Fibrous cap

Healthy artery wall Healthy artery wallHealthy artery wall Healthy artery wall Lipid pool

Lipid poolLipid pool Lipid pool

78.9 78.978.9 78.9 10.58 10.58 10.58 10.58 0.1 0.10.1 0.1

23.7 23.7 23.7 23.7 24.53 24.5324.53 24.53 0.0 0.0 0.0 0.0

26.3 26.326.3 26.3 22.13 22.1322.13 22.13

- - - -

0 0 0 0 212121 21 - -- -

Holzapfel model:

k

1

k

₂

β c

Fibrous cap

Healthy artery wall Lipid core

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23

5/Results

According to the parametric study:

• the fibrous cap thickness

• the material property of each component

• the stenosis severity S

• the plaque length L

• the plaque asymmetry As

• the slope upstream stenosis

• the shapes irregularities

Strain and stress analysis at systole

k 1

Systole

Time

16/ 23

(24)

5.1/Compression vs shear

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25

5.2/ Pinching effect

Short and severe plaques are pinched by the blood flow. The ’’Pinching Effect’’ comes from:

• the upstream

compression applied by the global flow

• the downstream compression by the recirculation

18/ 23

T. Belzacq, S. Avril, E. Leriche, A. Delache. Modelling of fluid structure interactions in stenosed arteries: effect of plaque deformability. Computer Methods in Biomechanics and Biomedical Engineering, 2010, 13(S1)25-26.

T. Belzacq, S. Avril, E. Leriche, A. Delache. A numerical parametric study of the mechanical action of pulsatile blood flow onto axisymmetric stenosed arteries. Medical Engineering and Physics. Revised.

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5.3/Experimental study

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27

5.4/Experimental and numerical comparaison

20/ 23

Similitude between average experimental and numerical results

(28)

5.5/More complex geometry

The ’’Pinching Effect’’ is amplified by:

• the shapes irregularities (number of bumps, amplitude of the bumps)

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29

6/Conclusion

Our study demonstrates clearly the inadequacy of the stenosis severity as the only criterion in evaluating the risk of plaque fracture.

Other parameters :

• the fibrous cap thickness

• the material properties

• the plaque length

• the shapes irregularities

• the slope upstream stenosis

• the plaque asymmetry

are found to have substantial effects on the fluid structure interaction (deformation, stress, flow patterns) and on the plaque vulnerability.

symptomatic plaque or

asymptomatic plaque Our parameterization

Clinical study

22/ 23

(30)

EXPERIMENTAL WORK ON ANEURISMS EXPERIMENTAL WORK ON ANEURISMS EXPERIMENTAL WORK ON ANEURISMS EXPERIMENTAL WORK ON ANEURISMS

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31

ascending aorta

descending aorta

(thoracic aorta and abdominal aorta)

arch of aorta ▶ a local dilation of the aorta

due to aortic wall weakening

a fatal medical emergency aneurysm rupture

Aortic aneurisms

(32)

Numerical Numerical simulations Numerical Numerical simulations simulations aimed simulations aimed aimed aimed at at at at supporting supporting supporting supporting the the the the surgical

surgical surgical

surgical decision decision decision decision

Towards predictive models?

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33

Experimental considerations

Usual Usual Usual Usual protocol protocol protocol protocol::::

T ru e s tr e s s ( M P a )

True strain

diastole systole

Physiological modulus

Stress – Strain curve

[Duprey et. al., In-vitro characterisation of physiological and maximum elastic modulus of ascending thoracic aortic aneurysms using uniaxial tensile testing, Eur. J. Vascular & Endovascular Surgery, 2010]

(34)

longitudinal

circumferential

σ = F/S =1.7 MPa

Vorp DA, Schiro BJ, Ehrlich MP, Juvonen TS, Ergin MA, Griffith BP. Effect of aneurysm on the tensile strength and biomechanical behaviour of the ascending thoracic aorta. Ann Thorac Surg 2003; 75(4):1210-4.

Failure properties

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35

W < 10 mJ/cm ²

Sommer G, Gasser TC, Regitnig P, Auer M., Holzapfel G.A. Dissection properties of the human aortic media: an experimental study. ASME J Biomech Eng 2008; 130:021007.

Fracture properties

(36)

A multi A multi A multi A multi- - - -layer layer layer layer material material material material

Passive Passive Passive Passive mechanical mechanical mechanical behavior mechanical behavior behavior behavior

Multi-layer

Matrix + different fibers

Arteries: a complex structure and behavior

Intima

Media

Smooth muscle cells Elastin

Elastin Elastin

Elastin fibers fibers fibers fibers Collagen Collagen Collagen

Collagen fibers fibers fibers fibers

Biologic sensor and filter

Adventitia Collagen Collagen Collagen Collagen fibers fibers fibers fibers

Anisotropy – Non linearities – Finite strains

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37

Anisotropic hyperelastic models for arteries

Hyperelasticity Hyperelasticity Hyperelasticity Hyperelasticity

Strain energy function:

2 ^nd Piola-Kirchhoff stress:

Anisotropic Anisotropic Anisotropic Anisotropic hyperelasticity hyperelasticity hyperelasticity hyperelasticity

( )

ψ = ψ E ^where ^E ⁼ ¹ ₂ ( ^{F F} ^T ^. ⁻ ^I )

= ∂ ψ S ∂

E

( ^, )

ψ = ψ E structure tensors

f

₁

f

₁

(38)

Anisotropic hyperelastic models for arteries

Fung Fung Fung Fung’’’’s s s s phenomenological phenomenological phenomenological phenomenological model model model model

Multilayered Multilayered Multilayered Multilayered Holzapfel Holzapfel Holzapfel Holzapfel’’’’s s s s histology histology histology histology- - - -based based based model based model model model

e

z

e

θ

( )

¹ ¹

(

²

⁽

ⁱ

⁾

²

)

2

k λ - 1 i = fibre1,

fibre2

k ψ = c I -3 +

2 ∑ 2k e - 1

( ¹ )

2 Q 2 2

11 θθ 22 zz 12 θθ zz

ψ = c

e − ^with Q = a E + a E + 2a E E

[Fung, Biorheology of soft tissues, Biorheology, 1973]

isotropic anisotropic matrix fiber families

f

1

f

2

α

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39

Experimental method

Testing Testing Testing Testing system system system system

1

[Genovese, A video-optical system for time-resolved whole-body measurement on vascular segments, Optics and Lasers in Engineering, 2009]

(40)

Experimental method

Reconstruction of Reconstruction of Reconstruction of Reconstruction of displacement displacement displacement displacement field field field field

Radial displacement

→ Pre-conditionning

8 cycles pressure

→ Applying pre stretch

λ

_z

= 1.1

→ Applying pressure:

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41

Experimental method

Derivation Derivation Derivation Derivation of of of of strain strain strain strain fields fields fields fields

Circumferential Green Lagrange strain

(42)

Identification by Virtual Field Method

Assuming Assuming Assuming Assuming constitutive constitutive constitutive constitutive parameters parameters parameters parameters

ψ T

= ρ .sym     ∂ ∂     . + p

σ F F I

E

( )

¹ ¹

(

²

⁽

ⁱ

⁾

²

)

2

k λ - 1 i = fibre1,

fibre2

c k

ψ = I -3 +

2 ∑ 2k e - 1

(43)

43

Identification by Virtual Field Method

Reconstruction of Cauchy stress Reconstruction of Cauchy stress Reconstruction of Cauchy stress Reconstruction of Cauchy stress field field field field

Circumferential Cauchy stress

Axial

Cauchy stress

(44)

Identification by the Virtual Fields Method

Are stresses Are stresses Are stresses Are stresses at at at at equilibrium equilibrium equilibrium equilibrium????

The following equations should be satisfied:

(principle of virtual work)

* *

ij ij i i

V V

- σ :ε dV + T u dS = 0

∫ ∂ ∫

( ) ^* ^*

ij ij i i

V V

- σ , A :ε dV + T u dS = 0

∫ ^E ∂ ∫

Equilibrium ⇔ Actual constitutive properties

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45

Identification by Virtual Field Method

Principle Principle Principle Principle of identification of identification of identification of identification

Iterative approach until reconstructed stresses minimize cost function J:

( ) ^ij ( ) ^* ^ij ⁱ ^* ⁱ ²

virtual fields pressure states V V

J A = - σ , A :ε dV + T u dS

∂

 

 

 

∑ ∑ ∫ ^E ∫

Internal Virtual Work

( IVW )

External Virtual Work

( EVW )

(46)

Identification by Virtual Field Method

Results Results Results Results of of of of optimization optimization optimization optimization

1 1.05 1.1 1.15 1.2 1.25

0 2 4 6 8 10 12 14 15 18

20 150

15 30 45 60 75 90 120 135

105

P re s s u re [ m m H g ]

0

P re s s u re [ k P a ]

λλλλ

Circumferential elongation λλλλ

Circumferential elongation

Experimental data

Neo Hookean

«Yeoh »

Fung exponential

Best fitting parameters:

(Holzapfel model, 1 layer)

Avril S, Badel P, Duprey A., Anisotropic and hyperelastic identification of in vitro human arteries from full-field optical measurements, Journal of Biomechanics, Volume 43, Issue

Holzapfel

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47

Characterizing Characterizing Characterizing Characterizing aneurismal aneurismal aneurismal tissue up to rupture aneurismal tissue up to rupture tissue up to rupture tissue up to rupture using

using using

using full full full full- - -field - field field data field data data data

(48)

ascending aorta

descending aorta

(thoracic aorta and abdominal aorta)

arch of aorta ▶ a local dilation of the aorta

due to aortic wall weakening

a fatal medical emergency aneurysm rupture

Aortic aneurisms

(49)

49

Deformation gradient Lagrange strain

Aneurismal

aortic tissue Inflation test Optical Full-field measurement ( Full-field displacement)

Inverse procedure

Application of the special Virtual Fields Method Identification of

material parameters Constitutive model

Calculation of stress at rupture

Methodology

(50)

an excised cylindrical aneurismal aortic tissue

a square specimen removing loose connective tissue

finding an appropriate location to separate

specimen is mounted on the inflation test device

making a speckle pattern separated layers two layers are pulled each other to separate cut

adventitia media

media

adventitia

x y

diameter: 30mm

Materials

(51)

51

inflation device cylinder

pressure gage

in vivo loading environments

(biaxial stress state due to internal pressure) can be generated

Inflation test

(52)

camera

Instron machine protector

Undeformed Deformed

x y

tracks the gray value pattern Digital image

stereocorrelation

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53

Theory of finite deformation

Deformation gradient F

Green-Lagrange strain tensor E = 1/2(C - I) right Cauchy-Green tensor C = F ^T F

Ux Uy Uz

from the undeformed and deformed

coordinates of each measurement data point

Assumption: plane stress

homogeneous initial thickness incompressibility

Measured displacement

fields

(54)

Identification by Virtual Field Method

Principle Principle Principle Principle of identification of identification of identification of identification

Iterative approach until reconstructed stresses minimize cost function J:

( ) ^ij ( ) ^* ^ij ⁱ ^* ⁱ ²

virtual fields pressure states V V

J A = - σ , A :ε dV + T u dS

∂

 

 

 

∑ ∑ ∫ ^E ∫

Internal Virtual Work

( IVW )

External Virtual Work

( EVW )

S. Avril, P. Badel, A Duprey. Anisotropic and hyperelastic identification of in vitro human arteries from full-field measurements. Journal of Biomechanics -2010, vol 43, N°15, pp 2978-2985.

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43.74 43.74 43.74 43.74ôôôô 37.35

37.3537.35 37.35ôôôô 37.12

37.12 37.12 37.12ôôôô 23.79

23.7923.79 23.79ôôôô 40.15

40.15 40.15 40.15ôôôô 57.7

57.7 57.7 57.7ôôôô αααα

2.3701 2.3701 2.3701 2.3701 5.175

5.175 5.175 5.175 5.1182

5.1182 5.1182 5.1182 9.8838

9.88389.8838 9.8838 1.963

1.9631.963 1.963 6.7701

6.77016.7701 6.7701 k

k k k₂₂₂₂

0.1186 0.1186 0.1186 0.1186 0.126

0.126 0.126 0.126 0.1744

0.1744 0.1744 0.1744 0.3072

0.30720.3072 0.3072 0.1333

0.1333 0.1333 0.1333 0.2858

0.28580.2858 0.2858 kk

kk₁₁₁₁((((MPaMPaMPaMPa))))

36, 38 mm 36, 38 mm36, 38 mm 36, 38 mm 32, 34 mm

32, 34 mm32, 34 mm 32, 34 mm 31, 43 mm

31, 43 mm 31, 43 mm 31, 43 mm 36, 39 mm

36, 39 mm36, 39 mm 36, 39 mm diameter

diameter diameter diameter (both ends) (both ends) (both ends) (both ends)

male, 76 male, 76 male, 76 male, 76 male, 69

male, 69 male, 69 male, 69 male, 68

male, 68 male, 68 male, 68 male, 81 years old

male, 81 years old male, 81 years old male, 81 years old sex, age

sex, age sex, age sex, age

(0.62mm) (0.62mm) (0.62mm) (0.62mm) (1.06mm)

(1.06mm)(1.06mm) (1.06mm) (1.09mm)

(1.09mm) (1.09mm) (1.09mm) (1.02mm)

(1.02mm)(1.02mm) (1.02mm) (0.91mm)

(0.91mm) (0.91mm) (0.91mm) (0.64mm)

(0.64mm)(0.64mm) (0.64mm) (thickness)

(thickness) (thickness) (thickness)

Adventitia Adventitia Adventitia Adventitia Media

Media Media Media Media

Media Media Media Adventitia

Adventitia Adventitia Adventitia Type

Type Type Type

66 66 555

5 44

44 333

3 22

22 111

1 CaseCase

CaseCase

▶ k ₂ is much higher aneurismal aortic tissue is stiffer than healthy aortic tissue

▶ measured fibre orientation angle α of the media is lower than that of the adventitia Results

f

1

f

2

α

(56)

the failure of aneurismal aortic tissue is oriented along preferred

x y

Rupture is characterized by oblique tears in the circumferential direction

Characterization of rupture

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57

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

0 0.2 0.4 0.6 0.8 1 1.2

0 0.1 0.2 0.3 0.4

strain

stress (MPa)

I

II

I

II

I II

III IV

I II

III IV

Media ( α ^<40 ^o ⁾ Adventitia

( α ^>40 ^o ⁾

circumferential direction ( σσσσ

xx

) axial direction ( σσσσ

yy

)

Stress strain curves

( )

¹

i = fibre1,

¹₂

( ^k

²

⁽ ^{λ - 1}

ⁱ

⁾

²

)

fibre2

c k

ψ = I -3 +

2 ∑ 2k e - 1 _Ψ _{’ = (1-D)} _Ψ

Damage!

(58)

p = 0.02 MPa 0.029 MPa 0.038 MPa 0.047 MPa

Rupture mode

A B

ε x

ε xy

ε y

Modes of rupture

(59)

59

Stress parameter at rupture

) ( cos )

(

sin ² α σ ² α σ

σ _α ^R = _xx ^R + _yy ^R

1.0522 0.3483

0.4107 0.3686

0.3719 0.6257

σ σ σ

σ

^R^R^R^Rα

((((MPa MPa MPa MPa))))

1.0933 1.09331.0933 1.0933 0.2958

0.29580.2958 0.2958 0.327

0.327 0.327 0.327 0.2163

0.21630.2163 0.2163 0.3398

0.33980.3398 0.3398 1.143

1.143 1.143 1.143

σ σ

^R^R^R^R_yy_yy_yy_yy

1.0073 1.0073 1.0073 1.0073 0.4384

0.4384 0.4384 0.4384 0.5568

0.5568 0.5568 0.5568 1.1524

1.1524 1.1524 1.1524 0.417

0.417 0.417 0.417 0.4189

0.4189 0.4189 0.4189 σ

σ σ σ

^R^R^R^Rxxxxxxxx

Cauchy stress at Cauchy stress at Cauchy stress at Cauchy stress at

rupture ( rupture ( rupture ( rupture (MPa MPa MPa MPa))))

adventitia adventitiaadventitia adventitia media

mediamedia media media

mediamedia media adventitia

adventitiaadventitia adventitia

type

type type type

6 6 6 6 5

5 5 5 4

4 4 4 3

3 3 3 2

2 2 2 1

1 1 1 Case

Case Case Case

the idea: the aneurysm rupture occurs in a preferred direction Stress at rupture

J. Kim, S. Avril, A Duprey, JP Favre. Experimental characterization of rupture in human aortic aneurysms using full-field measurement technique. Biomechanics and Modeling in

Mechanobiology. In press.

(60)

▶ the failure stress in the axial direction is much higher

in the adventitia layer (about three times) compared to that in the media layer

▶ the failure in the aneurismal aortic tissue may initiate in the media layer

▶ inflation test for the whole layer

even though the media ruptured,

only small hole or no damage was found in the adventitia

▶ means that the adventitia layer plays a very important role in preventing the artery from rupture

Modes of rupture

(61)

61

Future Future Future Future work work work work

(62)

Tissue engineering

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63

In vivo imaging

MRI MRI MRI MRI measurements measurements measurements measurements

S. Avril, F. Schneider, C. Boissier, ZY Li. In vivo velocity vector imaging and time-resolved strain rate measurements in the wall of blood vessels using MRI. Journal of Biomechanics, 2010, 44(5) pp 979-983.

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Students Students Students Students: : : Ambroise Duprey, Jin Kim, Alexandre Franquet, Nicolas : Demanget, Aaron Romo, Tristan Belzacq

Colleagues Colleagues Colleagues Colleagues::::

Dr Pierre Badel (Ecole des Mines Saint-Etienne) Dr Katia Genovese (Univ. Basilicata)

Prof Jean-Pierre Favre (Univ Hospital Saint-Etienne) Dr Alexandre Delache (Saint-Etienne University) Prof Emmanuel Leriche (Lille University)

Prof Valérie Deplano (Marseille University) Institutions and Institutions and Institutions and Institutions and funding funding funding funding partners partners partners:::: partners