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

Georgia Tech-University of Chicago

Prof. Ray Vito Prof. Sy 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

Farb, et al, Circ 1999

Stent Struts

Clinical Relevance to Coronary PTCI

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

Impact of Sy Glagov

Braunwald E.