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1377–1387
DOI: 10.1007/s10439-010-9916-6
calibration during post-processing. Care was taken to number of pixels between 5 lines (1 mm) on the cali-
ensure that the camera lens was parallel to the Petri bration slide. Points along the intima and adventitia
dish for each shot. surfaces were then manually selected. These points
In this study, the opening angle is characterized as were then used to calculate the inner and outer arc
an angle that increases in response to a stress-relieving length as well as the cross-sectional area of the vessel
cut. In the circumferential direction, the opening angle wall. Calculating the COA and LCA from the bisecting
F0 (COA) is defined as the angle between two lines that midpoint angle method described previously can be
bisects the midpoint of the inner sector wall and extend subjected to errors when selecting the midpoint loca-
to the inner edges (Fig. 2).1 In the longitudinal direc- tion at the inner wall, particularly in sectors that are
tion, we define a closing angle w0 analogous to the not ideally circular. Since the adventitia and intima
COA. We define it as the longitudinal ‘closing’ angle surfaces are well delineated in the images, we can use
(LCA) because this angle decreases or closes in instead the arc lengths of these boundaries along with
response to a stress-relieving cut. The opening angle n0 the cross-sectional area to calculate a more consistent
for the longitudinal direction (LOA) can therefore be COA or LCA that does not depend on selecting a
defined in terms of the closing angle w0 using the fol- midpoint. The COA and LCA (in radians) along with
lowing relationship (in radians) the thickness (t) calculated from this method are given
in the following equations
n0 ¼ p w 0 ð1Þ
Lo Li 2A
Note that the magnitude of the LOA defined in this COA; LCA ¼ p ; t¼ ð2Þ
2t Lo Li
study can vary depending on the length of the longi-
tudinal section. Although a length-independent mea- where A is the wall cross-sectional area, Lo and Li are
surement, such as curvature, may be calculated, since the outer and inner arc lengths, respectively, with Lo
each longitudinal strip was the same length we present being the arc length of the adventitia in circumferential
results in terms of LOA. sectors and the intima in longitudinal sectors. The
Image processing and measurements were made measurement program was validated by measuring the
using a custom MATLAB program. A reference length inner and outer diameters of a small metal cylinder
in each image was first calibrated by measuring the with known dimensions.
In conjunction with ANOVA, we utilized Tukey’s test direction the gradient of map from pðq; #; fÞ 7!
to determine specifically which means were statistically xðr; h; zÞ is
different. Pairs of statistically significant groups were
@r r
then analyzed with Student’s t-test to calculate their ½F2 ¼ diag ; ; kz ; ð4Þ
p-value. @q q
where kz ¼ ‘=Lu is the axial stretch ratio, ‘ is the loa-
ded length of the vessel, and Lu is the unloaded length
ANALYTICAL METHODS of the vessel in the traction-free configuration.
For a straight, axisymmetric tube, neglecting vari-
Kinematic Modeling ations along axial direction, since each material point
at a given radius r has the same deformation gradient,
Consider a local neighborhood kt about a point with
bn may be thought of as a set of discontinuous cylin-
position x(r, h, z) in the loaded configuration bt. Let
ders with radius Rn, axial length Ln, and infinitesimal
this neighborhood be denoted kn in the locally stress-
thickness dRn (Fig. 3). Since each ring is infinitesimally
free (or natural) configuration bn, which has position
thin, they cannot support a residual stress; thus, each
Xn(Rn, Hn, Zn) (Fig. 3). Let the gradient of the map
cylinder is stress-free. The map from Xn ðRn ; Hn ; Zn Þ 7!
Xn ðRn ; Hn ; Zn Þ 7! xðr; h; zÞ be denoted F. The natural
pðq; #; fÞ serves to ‘assemble’ the discontinuous
configuration bn is defined such that the local neigh-
stress-free cylinders into a continuous, albeit residu-
borhood about every point in the body is stress-free; in
ally stressed, tube; the gradient of this map may be
general, this configuration may be thought of as a set
defined as
of discontinuous elements. Note, bn is not experimen-
tally tractable. It is often convenient to decompose the F1 ¼ diagfKr ðqÞ; Kh ðqÞ; Kz ðqÞg; ð5Þ
map Xn ðRn ; Hn ; Zn Þ 7! xðr; h; zÞ into a map from
Xn ðRn ; Hn ; Zn Þ 7! pðq; #; fÞ and a map from where Kr (q), Kh (q), and Kz (q) are the stretch ratios of
pðq; #; fÞ 7! xðr; h; zÞ; where pðq; #; fÞ is the location of the infinitesimally thin cylinder that passes through
this material point in the traction-free (unloaded) point q in bu. If the stress-free configuration is known,
configuration bu; let the gradient of these maps be F1 then these stretch ratios may be calculated as
and F2, respectively, where q Lu
Kh ðqÞ ¼ ; Kz ðqÞ ¼ ;
F ¼ F2 F1 : ð3Þ Rn ðqÞ Ln ðqÞ
@q Rn ðqÞLn ðqÞ
For the inflation and extension of a long, straight, and Kr ðqÞ ¼ ¼ ; ð6Þ
@Rn qLu
axisymmetric tube, neglecting variations along axial
where Rn(q) and Ln(q) are the radius and axial length
of the stress-free cylinder in bn that passes through
radial location q in bu; incompressibility was assumed
in Eq. (6)3. Since Rn(q) and Ln(q) are not measurable,
experimentalists are forced to approximate the com-
ponents of Kr(q), Kh(q), and Kz(q) from experimentally
tractable quantities.
In traditional vascular mechanics, one typically
considers an experimentally measurable (nearly) stress-
free configuration bco taken as an excised arterial ring
that springs open when cut radially to relieve a large
part of the residual stress (Fig. 2; see Chuong and
Fung1). The mapping of points Xco ðR; h; ZÞ 7! pðq; #; fÞ
from bco to bu is defined as q = q(R), # = (p/Ho)H, and
f = KZ. Given this map, the deformation gradient Fc1,
has the components
@q pq
Fc1 ¼ diag ; ; Kz : ð7Þ
@R Ho R
FIGURE 3. The theoretical stress-free state consists of con-
centric cylindrical shells. Each shell is infinitesimally thin and The mean axial stretch ratio Kz is assumed to be
therefore stress-free. Circumferential and longitudinal resid- constant. That is, the changes in axial stretch with
ual strains develop as a result of radial and length incom-
patibility of the cylindrical shells as they are mapped to the radial location are ignored in this configuration and
traction-free state. the configuration bco is assumed to be a cylindrical
A Mechanical Analysis of Conduit Arteries 1381
sequence of this observation is that neither a cylindri- which may be evaluated with numerical integration
cal sector (bco) representing a radially cut ring nor a techniques.
cylindrical sector representing a curved longitudinal
strip ðb‘o Þ accurately represents a truly stress-free con-
figuration. Indeed, when both CRS and LRS are Stress Analysis
present, an experimentally tractable stress-free config- We modeled the artery to be a thick-walled cylin-
uration does not exist. Rather, a traction-free sector drical tube composed of an incompressible, orthotro-
deforms into a saddle shape (Fig. 4), which contain pic, homogeneous material undergoing an elastic
residual stresses. deformation of inflation and axial extension. We de-
Nevertheless, when the ratio of circumferential arc scribed the elastic property of the artery using a seven-
length to axial arc length is small (e.g., for a thin parameter exponential-type strain energy density
axial strip) the axial bending is only negligibly function of Chuong and Fung1 given as
affected by CRS. Thus, a thin axial strip may be used
to quantify the axial stretch Kz(q) from Eq. (6)2. c0
WðEÞ ¼ ðeQðEÞ 1Þ; ð13Þ
Similarly, as this aspect ratio becomes large (e.g., for 2
a thin radially cut ring), circumferential bending is where E ¼ 12ðFT F IÞ is the Green strain tensor, I is
only negligibly affected by LRS. Thus, a thin radially the identity tensor, and the exponential factor is given
cut ring may be used to quantify the circumferential by
stretch KH(q) (as done by Chuong and Fung1). Taken
together, we may approximate the components of Q ¼ c1 E2rr þ c2 E2hh þ c3 E2zz þ 2c4 Ehh Err þ 2c5 Ehh Ezz
F1 as þ 2c6 Ezz Err :
1382 R. WANG AND R. L. GLEASON JR.
RESULTS
280
120
240
90
200
60
160
30
120
80
0
1 2 3 4 5 6 1 2 3 4 5 6 7 8
Section Number Section Number
240
180
200
150
160
120
120
90
80
60
40
0 30
-40 0
1 2 3 4 5 6
1 2 3 4 5 6 7 8
Section Number
Section Number
FIGURE 6. COA (panel a) and LOA (panel b) of the LAD
shown against the section number as individual data points FIGURE 7. COA (panel a) and LOA (panel b) in the CCA shown
and the mean 6 SD (dashed line with error bars). The mean of against the section number. Figures show individual data
the COA appears to have a parabolic trend, but no signifi- points along with the mean 6 SD (dashed line with error bars).
cance when statistically analyzed. Analysis of the LOA reveals The COA appears to have a parabolic trend, but no significance
one significant section, number 6, compared to section 1. The when analyzed statistically. Individual data points reveal a
mean LOA appears to have an increasing trend. * p £ 0.05 minimum COA for each vessel that is significantly different
compared to section 1. from the surrounding sections. However, the section number
of the minimum value varies between vessels. ANOVA reveals
statistically significant relationship between LOA and section
number. Further analyses using Tukey’s and t-test show that
Stress Analysis Results the LOA of higher section numbers are statistically greater than
lower ones. * p £ 0.05 compared to sections 1, 2, and 3.
The inner and outer radii of the CCA in the trac- ** p £ 0.001 compared to sections 1, 2, 3, and 4.
tion-free configuration were qi = 2.18 mm and
qa = 3.46 mm, respectively. The segment length was
Lu = 10.1 mm. The inner radius of the circumferential during the biaxial mechanical test. The longitudinal
stress-free sector was Ri = 4.43 mm and the inner stress-free measurements were taken on strips cut distal
radius of the longitudinal stress-free sector was to the ring. All stress-free configuration measurements
Si = 5.34 mm. COA and LCA were measured to be were taken after mechanical testing.
Fo = 79.4 and wo = 117.9 respectively, correspond- The stretch ratios without LRS (i.e., diagonal
ing to approximately sections 6–7 (see Fig. 7). The components of the deformation gradient Fc1) agree with
thickness of this segment was larger than the nominal results by Choung and Fung,1 where the axial stretch
CCA thickness shown in Fig. 8b. The mean circum- ratio is K = 1. In their Fig. 2a the circumferential
ferential ðKH Þ and axial ðKz Þ stretch ratios were stretch ratio changes from a compressive state to a
assumed to be 1. The traction-free and circumferential tensile state at the mid-wall (see our Fig. 9a). Inclusion
stress-free measurements were made on a ring cut of LRS dramatically altered the stretch ratios as
from the location where diameter was being measured calculated via Eq. (5) with Eqs. (6) and (11) (Fig. 9b).
1384 R. WANG AND R. L. GLEASON JR.
1.3
0.8 λz
1.2
Stretch Ratio, λ
0.7
1.1
0.6 1
0.9
0.5
0.8
0.4
0.7
0.3 0.6
0.2 0.5
1 2 3 4 5 6 1 1.1 1.2 1.3 1.4 1.5 1.6
λθ
1.3
λz
1.4
Stretch Ratio, λ
1.2
1.1
1.2
1
1 0.9
0.8
0.8
0.7
0.6 0.6
0.5
0.4 1 1.1 1.2 1.3 1.4 1.5 1.6
1 2 3 4 5 6 7 8
Normalized Radius (R/Ri)
Section Number
FIGURE 9. Distributions of stretch ratios through the arterial
FIGURE 8. Changes in wall thickness for LAD (panel a) and
wall in the unloaded state without (panel a) and with (panel b)
CCA (panel b) shown against the section number. Individual
LRS plotted against normalized radius. Accounting for LRS
data points are presented as well as the mean 6 SD (dashed
dramatically changes the axial stretch ratio by altering the
line with error bars). ANOVA reveals that the thicknesses from
inner portion of the wall to be under compressive stretch and
both vessels are statistically significant to the section number
outer wall to be under tensile stretch.
(p < 0.005 for LAD) and (p < 0.0005 for CCA). Further analyses
show statistically thinner sections with higher section num-
bers. For LAD, * p £ 0.05 and ** p £ 0.001 compared to sec- TABLE 1. Material parameters calculated through regres-
tion 1. For CCA, *p £ 0.05 compared to section 1. sion analysis.
c (kPa) c1 c2 c3 c4 c5 c6 % Error
Most notably, the longitudinal stretch ratio changes
from a constant to a varying distribution in which the LRS 93.367 1.075 0.452 0.612 0.491 0.248 0.416 3.27
inner-wall is in compressive stretch and the outer-wall +LRS 137.930 1.019 0.350 0.518 0.463 0.232 0.438 3.49
in tensile stretch. This agrees intuitively with the
observed bending of a longitudinal sector into a gradient by 3-fold. In the longitudinal direction,
straight beam, which would require that the top of the analysis without LRS resulted in Dtzz = 28.82 kPa
beam (adventitia) be under tension and the bottom (Fig.10a dashed line) and analysis with LRS resulted in
(intima) be under compression. Dtzz = 163.27 kPa (Fig.10b dashed line), increasing the
Material parameters solved by our regression anal- gradient approximately 5.7-fold.
ysis without including LRS (LRS) and with LRS
(+LRS) are presented in Table 1. The stress gradients
Dthh and Dtzz (the maximum stress minus the minimum DISCUSSION
stress) were calculated for each analysis. For the cir-
cumferential direction without LRS Dthh = 73.58 kPa Numerous studies have demonstrated well that
(Fig.10a dotted line) and inclusion of LRS resulted in vascular cells possess the remarkable ability to sense
Dthh = 23.88 kPa (Fig.10b dotted line), reducing the and respond to changes in their local mechanical
A Mechanical Analysis of Conduit Arteries 1385
150 tz
section number. The LAD exhibited more complex
120 residual deformations apart from the longitudinal and
90 circumferential bending. As seen in certain longitudi-
nal sectors in Fig. 5a, although these sectors are nearly
60
circular, some possess a twist. Twists were also
30 observed in the circumferential sectors. This indicates a
0 residual shear deformation in some LAD sections. The
-30
variability in the COA was too large to observe any
1 1.1 1.2 1.3 1.4 1.5 1.6 statistical significance. As a result, we were not able to
Normalized Radius (R/R i) extract any relationship between the LOA and COA.
In the carotid arteries, the LOA increased with the
Panel (b) section number. We were not able to see any statisti-
210
tr
cally significance for the COA. Observed individually,
180 tθ we realized each vessel had a point of lowest COA that
Cauchy Stress (kPa)
Panel (b)
180 intima may be neglected. In several additional porcine
CCA, we removed the adventitial layer and measured
150 the COA and LOA. Both the COA and LOA were
comparable to the experimental findings of vessels with
120
the adventitia intact; this finding is comparable to
90
reports elsewhere for the COA.5,9,10 Thus, it appears
that both COA and LOA exist in the media (which may
60 be nearly homogeneous) and are not solely a function
of kinematic and material differences between the
30 media and adventitia. In addition, the experimental and
computational approaches presented herein could eas-
0
ily be extended to multi-layered vessels.
1 2 3 4 5 6 7 8 9 10 11 12 The existence of residual strains in the traction-free
Normalized Section Number state is a consequence of tissue development, growth,
FIGURE 11. Normalizing the section number based on the and remodeling which occur in the physiologically
smallest COA for the each CCA reveals a more apparent trend loaded state. It has been argued that cells grow and
between the COA and LOA to the location. ANOVA reveals remodel to restore the mechanical environment in the
statistical significance for COA and LOA between normalized
sections 1–11 (p £ 0.0005). Further analysis on the COA data local neighborhood in which they live.11 The conse-
shows that normalized sections 1–5 and 6–11 are statistically quence of this hypothesis is that the stresses (or perhaps
greater than section 7, * p £ 0.05. Normalized sections 1–5 are the strains) in the physiologically loaded configuration
statistically greater than normalized section 6, p £ 0.05.
Analysis on the LOA shows that higher sections (starting would be uniform throughout the tissue. Indeed, our
from normalized section 7) are statistically greater than lower findings suggest that the circumferential stress is nearly
sections, * p £ 0.05. This appears to show that as the COA uniform across the vessel wall under physiological
decrease towards the lowest point, the LOA increase simul-
taneously; possibly as a compensation mechanism to main- loading. The axial stress, however, is highly non-uni-
tain the circumferential stress gradient. Figure shows form across the wall. Limitations of the assumption
individual data points along with the mean 6 SD (dashed line that the material is homogeneous aside, these results
with error bars). Section 12 was not included in the analysis
since it has only a sample size of 1. suggest that the smooth muscle cells, which are oriented
in the circumferential direction, preferentially restore
tractions in the circumferential direction, compared to
had a sample size of 1. Normalizing the LOA revealed the axial direction. The non-uniform axial stress results
that the higher sections starting from section 6 were in high tension in the adventitia layer. For the carotids,
statistically significant from the lower sections. The which do not have much perivascular support, a tensile
most important relationship to observe is that as the adventitia in the axial direction may be favorable in
COA nears the lowest value (between normalized sec- stabilizing the artery from buckling during physiologi-
tions 6–7), the LOA begins to increase. Our thickness cal loading. This, however, does not explain why the
measurements indicate that the wall is thinner at higher coronary arteries, which are sufficiently embedded in
section numbers (Fig. 8b), therefore a decrease in COA perivascular support, also possess LRS. We believe that
along with a decrease in thickness, would result in the residual deformations of the coronary arteries have
A Mechanical Analysis of Conduit Arteries 1387
4
additional complexities due to the twisting of the lon- Fung, Y.-C., and S. Lui. Change of residual strains in
gitudinal strips observed experimentally. These specu- arteries due to hypertrophy caused by aortic constriction.
Circ. Res. 65:1340–1349, 1989.
lations, however, warrant further investigation. 5
Greenwald, S. E., J. E. Moore, A. I. Rachev, T. P. C.
In conclusion, we present evidence that circumfer- Kane, and J.-J. Meister. Experimental investigation of the
ential and longitudinal residual strains coexist at many distribution of residual stress in the artery wall. J. Biomech.
locations in porcine carotid and coronary arteries and Eng. 119:438–444, 1997.
6
that incorporation of these residual strains in stress Han, H. C., and D. N. Ku. Contractile responses in arteries
subjected to hypertensive pressure in seven-day organ
analysis significantly affects the predicted stress distri-
culture. Ann. Biomed. Eng. 29:467–475, 2001.
bution across the wall. We hope this study provides a 7
Holzapfel, G. A., G. Sommer, M. Auger, P. Regitnig, and
deeper breadth of understanding for the residual stress R. W. Ogden. Layer-specific 3D residual deformations of
states of an artery. human aortas with non-atherosclerotic intimal thickening.
Ann. Biomed. Eng. 35(4):530–545, 2007.
8
Humphrey, J. D. Cardiovascular Solid Mechanics: Cells,
Tissues, and Organs. New York: Springer-Verlag, 2001.
ACKNOWLEDGMENTS 9
Rachev, A. I., and S. E. Greenwald. Residual strains in
conduit arteries. J. Biomech. 36:661–670, 2003.
This research was supported by the National Insti- 10
Taber, L. A., and J. D. Humphrey. Stress-modulated
tute of Health Grant number R21-HL085822. The growth, residual stress, and vascular heterogeneity. J.
authors would like to thank Dr. Alexander Rachev for Biomech. Eng. 123:528–535, 2001.
11
his thoughtful discussions and insightful comments. Takamizawa, K., and K. Hayashi. Strain energy density
function and uniform strain hypothesis for arterial
mechanics. J. Biomech. 20:7–17, 1987.
12
Vaishnav, R. N., and J. Vossoughi. Residual stress
and strain in aortic segments. J. Biomech. 20:235–239,
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