As a follow-up to the work presented in Wenk et al. (2010, “Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Micromechanical Approximation,” ASME J. Biomech. Eng., 132, p. 091011), a formal sensitivity study was conducted in which several model parameters were varied. The previous work only simulated a few combinations of the parameters. In the present study, the fibrous cap thickness, longitudinal position of the region of microcalcifications, and volume fraction of microcalcifications were varied over a broader range of values. The goal of the present work is to investigate the effects of localized regions of microcalcifications on the stress field of atherosclerotic plaque caps in a section of carotid artery. More specifically, the variations in the magnitude and location of the maximum circumferential stress were assessed for a range of parameters using a global sensitivity analysis method known as Sobol' indices. The stress was calculated by performing finite element simulations of three-dimensional fluid-structure interaction models, while the sensitivity indices were computed using a Monte Carlo scheme. The results indicate that cap thickness plays a significant role in the variation in the magnitude of the maximum circumferential stress, with the sensitivity to volume fraction increasing when the region of microcalcification is located at the shoulder. However, the volume fraction played a larger role in the variation in the location of the maximum circumferential stress. This matches the finding of the previous study (Wenk et al., 2010, “Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Micromechanical Approximation,” ASME J. Biomech. Eng., 132, p. 091011), which indicates that the maximum circumferential stress always shifts to the region of microcalcification.

1.
Vengrenyuk
,
Y.
,
Carlier
,
S.
,
Xanthos
,
S.
,
Cardoso
,
L.
,
Ganatos
,
P.
,
Virmani
,
R.
,
Einav
,
S.
,
Gilchrist
,
L.
, and
Weinbaum
,
S.
, 2006, “
A Hypothesis for Vulnerable Plaque Rupture Due to Stress-Induced Debonding Around Cellular Microcalcification in Thin Fibrous Caps
,”
Proc. Natl. Acad. Sci. U.S.A.
0027-8424,
103
, pp.
14678
14683
.
2.
Bobryshev
,
Y. V.
,
Killingsworth
,
M. C.
,
Lord
,
R. S. A.
, and
Grabs
,
A. J.
, 2008, “
Matrix Vesicles in the Fibrous Cap of Atherosclerotic Plaque: Possible Contribution to Plaque Rupture
,”
J. Cell. Mol. Med.
,
12
, pp.
2073
2082
.
3.
Williamson
,
S. D.
,
Lam
,
Y.
,
Younis
,
H. F.
,
Huang
,
H.
,
Patel
,
S.
,
Mofrad
,
M. R. K.
, and
Kamm
,
R. D.
, 2003, “
On the Sensitivity of Wall Stresses in Diseased Arteries to Variable Material Properties
,”
ASME J. Biomech. Eng.
0148-0731,
125
, pp.
147
155
.
4.
Baldewsing
,
R. A.
,
de Korte
,
C. L.
,
Schaar
,
J. A.
,
Mastik
,
F.
, and
van der Steen
,
A. F. W.
, 2004, “
Finite Element Modeling and Intravascular Ultrasound Elastography of Vulnerable Plaques: Parameter Variation
,”
Ultrasonics
0041-624X,
42
, pp.
723
729
.
5.
Finet
,
G.
,
Ohayon
,
J.
, and
Rioufol
,
G.
, 2004, “
Biomechanical Interaction Between Cap Thickness, Lipid Core Composition and Blood Pressure in Vulnerable Coronary Plaque: Impact on Stability or Instability
,”
Coron. Artery Dis.
0954-6928,
15
, pp.
13
20
.
6.
Li
,
Z.
,
Howarth
,
S.
,
Tang
,
T.
, and
Gillard
,
J. H.
, 2006, “
How Critical Is Fibrous Cap Thickness on Carotid Plaque Stability?: A Flow-Plaque Interaction Model
,”
Stroke
0039-2499,
37
, pp.
1195
1199
.
7.
Tang
,
D.
,
Yang
,
C.
,
Zheng
,
J.
,
Woodard
,
P. K.
,
Saffitz
,
J. E.
,
Sicard
,
G. A.
,
Pilgram
,
T. K.
, and
Yuan
,
C.
, 2005, “
Quantifying Effects of Plaque Structure and Material Properties on Stress Distributions in Human Atherosclerotic Plaques Using 3D FSI Models
,”
ASME J. Biomech. Eng.
0148-0731,
127
, pp.
1185
1194
.
8.
Vengrenyuk
,
Y.
,
Cardoso
,
L.
, and
Weinbaum
,
S.
, 2008, “
Micro-CT Based Analysis of a New Paradigm for Vulnerable Plaque Rupture: Cellular Microcalcifications in Fibrous Cap
,”
Mol. Cell. Biomech.
,
5
, pp.
37
47
.
9.
Wenk
,
J. F.
,
Papadopoulos
,
P.
, and
Zohdi
,
T. I.
, 2010, “
Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Micromechanical Approximation
,”
ASME J. Biomech. Eng.
0148-0731,
132
, p.
091011
.
10.
Wendelhag
,
I.
,
Wiklund
,
O.
, and
Wikstrand
,
J.
, 1996, “
On Quantifying Plaque Size and Intima-Media Thickness in Carotid and Femoral Arteries
,”
Arterioscler., Thromb., Vasc. Biol.
1079-5642,
16
, pp.
843
850
.
11.
Moreno
,
P. R.
,
Lodder
,
R. A.
,
Purushothaman
,
K. R.
,
Charash
,
W. E.
,
O’Connor
,
W. N.
, and
Muller
,
J. E.
, 2002, “
Detection of Lipid Pool, Thin Fibrous Cap, and Inflammatory Cells in Human Aortic Atherosclerotic Plaques by Near-Infrared Spectroscopy
,”
Circulation
0009-7322,
105
, pp.
923
927
.
12.
Virmani
,
R.
,
Burke
,
A. P.
,
Farb
,
A.
, and
Kolodgie
,
F. D.
, 2006, “
Pathology of the Vulnerable Plaque
,”
J. Am. Coll. Cardiol.
0735-1097,
47
, pp.
C13
C18
.
13.
Huang
,
H.
,
Virmani
,
R.
,
Younis
,
H.
,
Burke
,
A. P.
,
Kamm
,
R. D.
, and
Lee
,
R. T.
, 2001, “
The Impact of Calcification on the Biomechanical Stability of Atherosclerotic Plaques
,”
Circulation
0009-7322,
103
, pp.
1051
1056
.
14.
Hashin
,
Z.
, and
Shtrikman
,
S.
, 1962, “
On Some Variational Principles in Anisotropic and Nonhomogeneous Elasticity
,”
J. Mech. Phys. Solids
0022-5096,
10
, pp.
335
342
.
15.
Hashin
,
Z.
, and
Shtrikman
,
S.
, 1963, “
A Variational Approach to the Theory of the Elastic Behaviour of Multiphase Materials
,”
J. Mech. Phys. Solids
0022-5096,
11
, pp.
127
140
.
16.
Sobol'
,
I. M.
, 1993, “
Sensitivity Estimates for Nonlinear Mathematical Models
,”
Mathematical Modelling and Computational Experiments
,
1
(
4
), pp.
407
414
.
17.
Saltelli
,
A.
,
Chan
,
K.
, and
Scott
,
E. M.
, 2000,
Sensitivity Analysis
,
Wiley
,
Chichester
.
18.
Archer
,
G. E. B.
,
Saltelli
,
A.
, and
Sobol'
,
I. M.
, 1997, “
Sensitivity Measures, Anova-Like Techniques and the Use of Bootstrap
,”
J. Stat. Comput. Simul.
0094-9655,
58
, pp.
99
120
.
19.
Homma
,
T.
, and
Saltelli
,
A.
, 1996, “
Importance Measures in Global Sensitivity Analysis of Nonlinear Models
,”
Reliab. Eng. Syst. Saf.
0951-8320,
52
, pp.
1
17
.
20.
Holzapfel
,
G. A.
,
Sommer
,
G.
, and
Regitnig
,
P.
, 2004, “
Anisotropic Mechanical Properties of Tissue Components in Human Atherosclerotic Plaques
,”
ASME J. Biomech. Eng.
0148-0731,
126
, pp.
657
665
.
21.
Kolodgie
,
F. D.
,
Nakazawa
,
G.
,
Sangiorgi
,
G.
,
Ladich
,
E.
,
Burke
,
A. P.
, and
Virmani
,
R.
, 2007, “
Pathology of Atherosclerosis and Stenting
,”
Neuroimaging Clin. N. Am.
1052-5149,
17
, pp.
285
301
.
22.
Bluestein
,
D.
,
Alemu
,
Y.
,
Avrahami
,
I.
,
Gharib
,
M.
,
Dumont
,
K.
,
Ricotta
,
J. J.
, and
Einav
,
S.
, 2008, “
Influence of Microcalcifications on Vulnerable Plaque Mechanics Using FSI Modeling
,”
J. Biomech.
0021-9290,
41
, pp.
1111
1118
.
23.
Li
,
Z.
,
Howarth
,
S.
,
Tang
,
T.
,
U-King-Im
,
J.
, and
Gillard
,
J. H.
, 2007, “
Does Calcium Deposition Play a Role in the Stability of Atheroma? Location May Be the Key
,”
Cerebrovasc Dis.
1015-9770,
24
, pp.
452
459
.
24.
Roijers
,
R. B.
,
Dutta
,
R. K.
,
Cleutjens
,
J. P. M.
,
Mutsaers
,
P. H. A.
,
de Goeij
,
J. J. M.
, and
van der Vusse
,
G. J.
, 2008, “
Early Calcification in Human Coronary Arteries as Determined With a Proton Microprobe
,”
Anal. Chem.
0003-2700,
80
, pp.
55
61
.
You do not currently have access to this content.