Biomechanics of Heterogeneous Arteries & The Implications for Medical Device R&D Deborah Kilpatrick, PhD Program Manager New Ventures Group, Guidant Corporation Hemodynamics & Vascular Remodeling Symposium in Honor of Dr. Seymour Glagov
Dec 15, 2015
Biomechanics of Heterogeneous Arteries&
The Implications for Medical Device R&D
Deborah Kilpatrick, PhD
Program Manager New Ventures Group,Guidant Corporation
Hemodynamics & Vascular Remodeling Symposium in Honor of Dr. Seymour Glagov
Arterial Structure & Function
arterial medial structure
Clark & Glagov, Arterioscl 1985
Glagov et al, NEJM 1987
arterial remodeling in atherosclerosis
Complex Constitutive Behavior• nearly incompressible, viscoelastic solid with residual stresses
• characteristic soft tissue nonlinearity
Multiaxial, Finite Deformation
• up to 100% ii possible
Anisotropy• orientation of ECM proteins, SMC important
Heterogeneity • cellular and ECM composition variable with patient, age, etc.,
and DISEASE
• histology & histochemistry dependent behavior
Complex Constitutive Behavior• nearly incompressible, viscoelastic solid with residual stresses
• characteristic soft tissue nonlinearity
Multiaxial, Finite Deformation
• up to 100% ii possible
Anisotropy• orientation of ECM proteins, SMC important
Heterogeneity • cellular and ECM composition variable with patient, age, etc.,
and DISEASE
• histology & histochemistry dependent behavior
Clark & Glagov, 1985
Impact of Structure on Biomechanics
Kilpatrick, Xu, Vito, Glagov
Atherosclerosis & Heterogeneity
Virmani et al 2000
• Constitutive laws are different• Deformation behavior changes• Material symmetry is altered• Heterogeneity becomes a BIG issue
So, how do we deal with heterogeneity in terms of overall behavior?
local biaxial (R,) transmural deformationlocal biaxial (R,) transmural deformation
Arterial Biomechanics on Local Scale
X
Y
displacemt field=f(r,)
positioner
artery
chamber
CCD
1 (dynes/cm2)= 0.1 Pa
CONSTITUENT
E1(dynes/cm2)
E2(dynes/cm2)
o
LIPIDACCUMULATIONS
3.81x104
3.88x105
.182
DISEASE-FREEMEDIA TISSUE
6.15x105 2.45x106 .137
FIBROUS INTIMAL TISSUE
4.83x106 1.82x107 .082
CALCIFIC REGIONS
3.99x107 1.07x108 .053
Assumes incrompressible, isotropic, bilinear elasticity.
straino
stress E2
E1
Kilpatrick-Beattie et al, J. Biomech. Eng., 1998.Kilpatrick-Beattie et al, J. Biomech. Eng., 1998.
Tissue Component Mechanical Properties
Braunwald E.
•Disease free media•Lipid accumulations•Fibrous intima or cap•Calcific regions
0
0.2
0.4
0.6
0.8
1
y(c
m)
-0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1
x(cm)
L L
H
H
F
F
H=HEALTHY
L=LIPID
F=FIBROUS
HISTOLOGY
-0 .60 -0 .40 -0 .20 -0 .00 0.20 0.40 0.60 0.80
0.20
0.40
0.60
0.80
0
200000
600000
1000000
1400000
1800000
2200000
2600000
3000000
3400000
3800000
4000000
MAXIMUM PRINCIPAL STRESS
MAX
X(cm)
Y(c
m)
HISTOLOGY
L = lipid accumulationsH = disease-freeF = fibrous intima
dynes/cm2
Biomechanics Reflects Pathology
MMP-1
LUMENSURFACE
Kilpatrick et al, J. Mech. Med. Biol., 2002.Kilpatrick et al, J. Mech. Med. Biol., 2002.
1.0E+00
1.0E+01
1.0E+02
1.0E+03
1.0E+04
1.0E+05
1.0E+06
1.0E+07
1.0E+08
1.0E+09
1.0E+00 1.0E+01 1.0E+02 1.0E+03 1.0E+04 1.0E+05 1.0E+06 1.0E+07 1.0E+08 1.0E+09stress
(dynes/cm2)
stra
in e
nerg
y(d
ynes
/cm
2)
L
H
F
C
M M P1
LAPLACE
lipidlipidlipidlipid
Stress (dynes/cm2)
Str
ain
En
erg
y (
dy
ne
s/c
m2 )
Can therapeutic strategies be designed to selectively invoke/suppress certain responses?
Can therapeutic strategies be designed to selectively invoke/suppress certain responses?
Laplace
Histology, Histochemistry, & Biomechanics
disease-free mediadisease-free mediadisease-free mediadisease-free media
MMP-1MMP-1MMP-1MMP-1
fibrous intimafibrous intimafibrous intimafibrous intimaCaCa++++CaCa++++
Kilpatrick-Beattie et al, J. Biomech. Eng., 1998.Kilpatrick-Beattie et al,
J. Biomech. Eng., 1998.
• What happens at the tissue-device interface?
• How could artery/lesion biomechanical behavior drive device design, and vice-versa?
Impact on Medical Device R&D
Vessel/plaque Modeling
Device Application
norm
alized
Tissue Mechanical Testing
human LAD
porcine LAD
Tissue-Device Interaction R&D
Feezor et al, Proc. ASME Summer Bioeng Conf, 2001.Data on file at Guidant.
intact coronary transmural P- deformationintact coronary transmural P- deformation
Tajaddini et al, J. Biomech. Eng., 2003
HP SONOSIVUS imaging30 MHz, 30 fps
intact LAD on myocardial
bedIVUS catheter
online pressureand temperaturemonitor
Pressure pumpand saline tank
proximal & local lumen pressure monitor
thermal thermal controlcontrol
pressurepressurecontrolcontrol
environmental chamber
access via left main ostium
The Cleveland Clinic Foundation
Intact Coronary Biomechanics
Biomechanics of PTCI in CAD
lipid
lipid
Feezor et al, 2003 ASME Summer Bioeng Conf, submitted.Model developed at Guidant.
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
11.0
12.0
13.0
14.0
15.0
Fibroatheroma A Fibroatheroma B
Ave
rag
e S
ho
uld
er S
tres
s (M
Pa)
fibroatheroma A
fibroatheroma B
Feezor et al, 2003 ASME Summer Bioeng Conf, submitted.Model developed at Guidant. Data on file at Guidant.
Biomechanics Reflects Pathology (yet again!)
Model-Predicted Lesion Shoulder Stress in PTCI