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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Tissue Biomechanics
Philippe K. Zysset
Institute for Lightweight Design and Structural BiomechanicsVienna University of Technology, Austriahttp://www.ilsb.tuwien.ac.at
Einfuhrung in die Biomedizinische Technik, Wien den 9. Oktober 2009
TU Wien Ph. Zysset
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Outline
1 Introduction
2 MCF, Lamella & BSU
3 Tissue
4 µCT
5 pQCT
6 HR-QCT
TU Wien Ph. Zysset
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Outline
1 Introduction
2 MCF, Lamella & BSU
3 Tissue
4 µCT
5 pQCT
6 HR-QCT
TU Wien Ph. Zysset
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
The Bone Syndrome
TU Wien Ph. Zysset
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Motivation
Metabolic bone diseases
Fractures
Implant fixation
The three ages of a woman (G. Klimt)
TU Wien Ph. Zysset
I d i MCF L ll & BSU Ti CT QCT HR QCT
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Osteoporosis
FACTS IN AUSTRIA
750’000 patients
1 out of 3 women
1 out of 7 men12’000 hip fx a year
Chronic pain and impair.
20% mortality after 70
12’000 Euros per hip fxKoeck et al., Wiener Klin Wochen,
2001.
Hip fracture
TU Wien Ph. Zysset
I t d ti MCF L ll & BSU Ti CT QCT HR QCT
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Osteoporosis
FACTS IN AUSTRIA
750’000 patients
1 out of 3 women
1 out of 7 men12’000 hip fx a year
Chronic pain and impair.
20% mortality after 70
12’000 Euros per hip fxKoeck et al., Wiener Klin Wochen,
2001.
Bone mass as a function of age
TU Wien Ph. Zysset
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Introduction MCF Lamella & BSU Tissue µCT pQCT HR QCT
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Bone Hierarchical Organisation
The Bench Top
The mineralized collagen fibril (MCF, 200nm)
The lamella (2-7µm)The bone structural unit (BSU, 60µm)
Bone tissue, cortical shell or trabeculae (100-3000µm)
Trabecular bone (TB, mm)
Organ (cm)
The Bedside
TU Wien Ph. Zysset
Introduction MCF Lamella & BSU Tissue µCT pQCT HR QCT
8/8/2019 Biomechanik Gewebe
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Outline
1 Introduction
2 MCF, Lamella & BSU
3 Tissue
4 µCT
5 pQCT
6 HR-QCT
TU Wien Ph. Zysset
Introduction MCF Lamella & BSU Tissue µCT pQCT HR-QCT
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Mineralized Collagen Fibril
Type I collagenApatite platelets
Water
Non-collagenous proteins
Currey, Princeton Press, 2002.
TU Wien Ph. Zysset
Introduction MCF Lamella & BSU Tissue µCT pQCT HR-QCT
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR QCT
Mineralized Collagen Fibril Array
Reisinger et al., work in progress.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR QCT
Lamellar Organization
Giraud-Guille, Calcif Tissue Int, 1988.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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, µ pQ Q
Bone Structural Unit
Eriksen et al., Raven Press, 1994.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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µ p
Mineralization and Orientation
Mean degree of mineralization
Polarized light microscopy (Paul Kasili)
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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µ
Outline
1 Introduction
2 MCF, Lamella & BSU
3 Tissue
4 µCT
5 pQCT
6 HR-QCT
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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Indentation Principle
t
P
h
P
t
t
h
t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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Indentation Principle
t
P
h
P
t
t
h
t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Indentation Principle
t
P
h
P
t
t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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Indentation Principle
t
P
h
P
t
t
h
t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Indentation Principle
t
P
h
P
t
t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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Indentation Principle
t
P
h
P
t
t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Indentation Principle
t
P
h
P
t
t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Indentation Principle
t
P
h
P
t
t
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t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Indentation Principle
t
P
h
P
t
t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Indentation Principle
t
P
h
P
t
t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Indentation Principle
t
P
h
P
t
t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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Indentation Principle
t
P
h
P
t
t
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t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
8/8/2019 Biomechanik Gewebe
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Indentation Principle
t
P
h
P
t
t
h
t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
I d i P i i l
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Indentation Principle
t
P
h
P
t
t
h
t
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
I d i P i i l
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Indentation Principle
t
P
h
P
t
t
h
t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
I d t ti P i i l
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Indentation Principle
t
P
h
P
t
t
h
t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
I d t ti P i i l
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Indentation Principle
t
P
h
P
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t
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
I d t ti P i i l
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Indentation Principle
t
P
h
P
t
t
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t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Indentation Principle
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Indentation Principle
t
P
h
P
t
t
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t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Indentation Principle
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Indentation Principle
t
P
h
P
t
t
h
t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Indentation Principle
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Indentation Principle
t
P
h
P
t
t
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t
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Indentation of Isotropic Materials
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Indentation of Isotropic Materials
dP
dh
hmax
Pmax
0.5 1.0 1.5h
2
4
6
8
10P
Oliver and Pharr (1992)
R E =
√π dP
dh(hmax )
2 A(hmax )
=E s
1− ν 2s +
E t
1− ν 2t
I E =
E s
1
−ν 2s
Oliver & Pharr, J Mater Res, 1992.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Indentation in Anisotropic Materials
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Indentation in Anisotropic Materials
I E (S, a3) =
4π 2π
0
B−1(t(γ ), S) : [a3 ⊗ a3]
(a1/a2) cos2 γ + (a2/a1) sin2 γ dγ
Swadener & Pharr, Phil Mag, 2001.
M min max
m1
-10
0
10m2
-20
-10
0
10
20
m3
-10
0
10
m1
m1
m2
m3
m1
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Human Vertebral Shell
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Human Vertebral Shell
0
10
10
0
10
20
0
20
32.6
50.2
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Human Vertebral Endplate
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Human Vertebral Endplate
20
10
0
10
20
20
10
0
10
20
10
0
10
31.8
39.5
Mazza et al., unpublished.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Trabecular tissue
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Trabecular tissue
10
0
10
10
0
10
20
10
0
10
20
39.
43.5
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Outline
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Outline
1 Introduction
2 MCF, Lamella & BSU
3 Tissue
4 µCT
5 pQCT
6 HR-QCT
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Trabecular Bone Morphometry
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Trabecular Bone Morphometry
Volume fraction BV/TVArea density BS/TV
Trabecular thickness TbTh
Trabecular separation TbSp
Trabecular number TbNbConnectivity density Conn.Dens.
Structure Model Index SMI
Individual plates and rods
Odgaard & Gundersen, Bone, 1993.Hildebrand & Ruegsegger, Comput Method Biomech, 1997.Hildebrand et al., J Bone Miner Res, 1999.Stauber et al., J Bone Miner Res, 2006.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Fabric
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Fabric
M =
3i =1
mi Mi =
3i =1
mi (mi ⊗mi )
Harrigan & Mann, J Mater Sci, 1984.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Fabric-based Elasticity
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y
C(ρ, M) =3
i =1
1
ǫ0ρk m2l i
Mi ⊗Mi
−3
i < j =1
ν 0ǫ0ρk ml
i ml j
(Mi ⊗M j + M j ⊗Mi )
+
3i < j =1
1
2µ0ρk ml i m
l j
(Mi ⊗M j + M j ⊗Mi )
ǫ0, µ0 and ν 0 are elastic constants of an asymptotic cubic material withρ = 1,m1 = m2 = m3 = 1 and k , l are exponents.
Zysset & Curnier, Mech Mater, 1995.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Fabric-based Elasticity
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y
S
S
SS
SS
S
SSS
S
SS
S S
S S
S
S
S
S
SS
S
RRR
R RRRR
RR
RR
R
RR
T
T
TT
TTT
T
T T
TTTT
TT
TT
T
T
TT
T
T
TTTT
TT
TT
T T
T
TTT
TT T
T
T
T
T
TT
F
FF
FF
F
F F
FFF F
FF
FF
F
F
F
FFFFF
FFadj. R2
0.942
10 20 50 100 200 500 1000 200010
20
50
100
200
500
1000
2000
Experimental stiffness MPa
P r e d i c t e d s t i f f n
e s s
M P a
O Multiaxial
O Torsion
O Tension
O Compression
Rincon-Kohli and Zysset, Biomech Model Mechan, 2009.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
FE Models: Voxel versus Smooth Surface
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Voxel
Segmentation
Cubic elements (voxels)
Smooth Surface
Segmentation + surface
Tetrahedral elements
Pahr, unpublished.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Validation Experiment
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p
MicroCT at 20 µm
Mechanical testing
NanoindentationVoxel-based FEA
Sub-region FEA
Chevalier et al., J Biomech, 2007.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Mechanical Test & FE
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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Nanoindentation (dry)
MeanSD21.11.0 GPa
0 1 2 3 4 5 6 70
5
10
15
20
25
30
Samples
T i s s u e M o d u l u s G P
a
FE versus Experiments (dry)
R20.978
BVTV: 932
0 500 1000 1500 2000 2500 3000 35000
500
1000
1500
2000
2500
3000
3500
Experimental Modulus MPa
F E M o d u l u s M
P a
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Sensitivity Analysis
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Outline
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1 Introduction
2 MCF, Lamella & BSU
3 Tissue
4 µCT
5 pQCT
6 HR-QCT
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
pQCT Resolution
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Experimental Colles’ Fracture
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Varga et al., J Biomech, in press.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Experimental Colles’ Fracture
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Experimental Colles’ Fracture
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
pQCT of a 9mm Slice
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
FE Model of a 9mm Slice
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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adj.R20.689
0 50 100 150 200 250 3000
2000
4000
6000
8000
10000
vBMD mgcc
U l t i m a t e f o r c e
N
adj.R20.219
0.0 0.1 0.2 0.3 0.4 0.50
2000
4000
6000
8000
10000
CtTh mm
U l t i m a t e f o r c e
N
adj.R20.946
0 50 100 150 200 250 3000
2000
4000
6000
8000
10000
microFE stiffness kNmm
U l t i m a t e f o r c e
N
adj.R20.935
0 2000 4000 6000 8000 10 0000
2000
4000
6000
8000
10000
FE ultimate force N
U l t i m a t e f o r c e
N
Varga et al., unpublished
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
QCT Resolution
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Sub-study of the EUROFORS Clinical Trial
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Multicenter
44 post-menopausal women(68±6.7 y.o.)
Teriparatide 20µg/day
DXA L1-L4
HRQCT T12
0,6,12,24 months
Graeff et al., J Bone Mineral Res, online.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Voxel-Based Finite Element Modeling
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Model parameters:
Cubic elements of 1.3mm
Top and bottom PMMA layers
Density-based mat. properties
Homogeneous I-S architectureAxial loading
Output variables:
Stiffness:=load/displacementStrength:=maximum load
Distribution of damage Chevalier et al., ComputMethod Biomech, 2007.
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissueµ
CT pQCT HR-QCT
Results
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0.0 0.2 0.4 0.6 0.8 1.0
0
500
1000
1500
2000
2500
3000
3500
Displacement mm
F o r c
e N
Baseline
6 Mo
12 Mo
24 Mo
TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissueµ
CT pQCT HR-QCT
Results
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Increase of strength in %
6 12 2450
0
50
100
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Results
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Acknowledgments
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TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT
Acknowledgments
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AO Foundation, Switzerland - AO Research Institute, Switzerland - CAE, Austria -
Celtis, Austria - Eli Lilly & Company, Europe - ESRF, France - ETH Lausanne,Switzerland - ETHZurich, Switzerland - FWF, Austria - Inselspital Bern, Switzerland -
Institut fur Unfallchirurgische Forschung und Biomechanik, Germany - Kuros
Biosurgery, Switzerland - Laboratoire d’Imagerie Parametrique, France - Ludwig
Boltzmann Institut fur Experimentelle und Klinische Traumatologie, Austria - Ludwig
Boltzmann Institut fur Osteologie, Austria - Ludwig-Maximilians Universitat Munchen,
Germany - Max-Planck-Institut fur Kolloid und Grenzflachen Forschung, Germany -
Med Uni Wien, Austria - Paracelsus Medizinische Universitat, Austria - Politecnico di
Milano, Italy - Sanofi-Aventis, USA - Technical University Prague, Czech Republic -
Technische Universitat Hamburg-Harburg, Germany - Universitat Bern, Switzerland -
Universitatsklinik Schleswig-Holstein, Germany - Universitatsmedizin Berlin, Germany
- University of Leeds, Great Britain, Veterinarmedizinische Universitat Wien, Austria -
VINforce, Austria
TU Wien Ph. Zysset