Computational Fluid Dynamics

A new research tool for assessing

coronary physiology

Michail I. Papafaklis MD, PhD

Michailideion Cardiac Centre
Medical School, University of Ioannina
 Summary

„ Physiology and Hemodynamics

„ Computational analysis of blood flow and

blood flow simulation in coronary arteries

„ The role of hemodynamic forces in

coronary artery disease
 Physiology
„ Cardiology Is Flow
The primary aim of the cardiovascular system is to drive, control and
maintain blood flow to all parts of the body
Richter and Edelman Circulation 2006
„ Complexity of the circulatory system
„ The heart is an intermittent pump → blood flow in the arterial
circulation is pulsatile
„ The blood vessels are branched, distensible tubes of various
dimensions
„ The blood is a complex suspension
Despite this complexity, the function of the circulatory
system can be explained by the principles of basic
fluid mechanics that apply to non-biologic systems,
such as household plumbing systems
 Hemodynamics
„ The term “hemodynamics”
hemodynamics describes the physical
principles governing pressure, flow and resistance as
they relate to the cardiovascular system, and the flow of
blood in the vessels

„ Blood flow is determined by two factors:

„ A pressure difference between the two ends of a vessel or group
of vessels
„ The resistance that blood must overcome as it moves through
the vessel or vessels

Pressure (P) = Flow (Q) × Resistance (R)

1 peripheral resistance unit (PRU)=100mmHg/100ml·sec-1
 Fluid Mechanics
„ Stress (Pa) = Force (Nt) / Surface (m2)
„ Shear stress (tangential component)
„ Normal stress (vertical component)
„ Angular deformation
(strain) of fluids is
caused by shear stresses

„ Newtonian fluids
Shear stress = viscosity × Strain rate
„ Non-Newtonian fluids
Viscosity is not constant, but depends on the strain rate
 Hemodynamics
Components of hemodynamic stress
 Hemodynamics
Rheological properties of blood
„ Whole blood is a
concentrated suspension
of blood cells in plasma
(electrolytic solution of
inorganic and organic
molecules, and proteins)

„ Viscometric properties of
whole blood
„ Depend on Hct
„ Depend on the strain rate
(non-Newtonian fluid)
mainly in low strain rates
 Hemodynamics
Poiseuille flow
Q=(π/128μ)·P·d4/L τw = 32·μ·Q/π·d3
Jean Louis Marie Poiseuille (1799-1869)
Gotthilf Heinrich Ludwig Hagen (1797-1884)
„ Assumptions
„ Blood is considered to behave as a Newtonian fluid
„ The vessel is considered to be a straight tube with
rigid walls and constant circular cross-section
„ Blood flow is considered
to be steady, laminar and
fully-developed
 Coronary circulation
„ The coronary circulation net is the denser
capillary net in the human body
„ The resting coronary blood flow is
about 225 ml/min or about 0.8 ml/g
of the heart muscle
„ During exercise conditions the
coronary blood supply can increase
by 4 to 10 times the resting blood
flow rate
 Coronary circulation
Arteries
„ Coronary arteries are tubes with a non-circular
cross-section, which is progressively reduced in size
going distally (tapering)
„ Several bifurcations and branches are present
„ The arterial wall is distended in every heartbeat
(pressure wave)
„ Coronary arteries are situated on the epicardium and
follow its curvature
„ The geometry of the system is dynamic because of the
constant movement of the heart during every cardiac
cycle
„ Coronary blood flow is pulsatile
Most flow (mainly for the left coronary artery) occurs
during the diastolic phase of the cardiac cycle
 Hemodynamics
Differential analysis
„ Detailed description of the flow field and accurate computation of
hemodynamic parameters in all flow situations
Continuity equation Navier-Stokes equation

Cartesian coordinates
 Computational Fluid Dynamics

„ Computational techniques (use of computers) applied for

the numerical solution of the differential flow equations,
since a direct analytic solution for complex flow fields is
not feasible
„ A practical and reliable tool for studying the time-varying,
3D blood flow patterns in complex arterial geometries
„ CFD computations are based on a much more complex
flow model compared to Poiseuille flow and provide
useful info on spatial and temporal changes of
hemodynamic parameters (e.g. flow velocity near the
vessel wall and shear stress)
„ CFD allows the simulation of the hemodynamic
environment under controlled conditions
 Computational Fluid Dynamics
General Principles of the method

„ In CFD modelling a complex geometry is

discretized into a large number of smaller
but regular (typically, tetrahedral or
hexahedral) elements → computational
mesh
„ Numerical solution of the differential equations
of motion at the nodes connecting these
elements after applying certain boundary
conditions
„ Computation of hemodynamic quantities
(pressure, velocity components, shear stress)
 Computational Fluid Dynamics
Application in human vessel models

„ CFD was initially applied in theoretical idealized

computer models of various vessels (aorta, carotids,
coronary arteries, aorto-coronary bypass grafts)
„ These idealized computer vessel models were based on
mean measurements from cadaver specimens or
angiographic data
„ However, normal anatomic differences from one person
to another cause great variations in terms of
hemodynamics and necessitate the incorporation of the
detailed arterial characteristics of every person in CFD
modelling
„ In order to achieve blood flow simulation for every vessel
and every patient, the most important element is real 3D
reconstruction of the lumen vessel → patient-specific
arterial models
 Computational Fluid Dynamics
3D coronary artery reconstruction
„ Anatomic characteristics of coronary arteries
„ Small dimension (mean diameter ≈ 3mm)
„ 3D complex (epicardial curvature) and time-dependent geometry
(heart movement)
„ Fusion of coronary angiography and intravascular
ultrasound (IVUS) data
„ Coronary angiography
„ Geometry of coronary artery lumen
„ Position and geometry of IVUS catheter in the arterial lumen
„ IVUS
„ Detailed geometry of the lumen and arterial wall (atheromatic
plaque) in every cross-section
Computational Fluid Dynamics
3D coronary artery reconstruction

Point cloud of the

Point cloud of the lumen
outer vessel wall

Bourantas et al. Comput Med Imaging Graph 2005

 Computational Fluid Dynamics
3D coronary artery reconstruction
3D lumen & outer 3D lumen & outer
Point clouds of the vessel wall vessel wall
lumen & reconstruction reconstruction
outer vessel wall LAO view RAO view

Papafaklis MI. PhD Thesis 2008

Bourantas et al. Comput Med Imaging Graph 2005
 Computational Fluid Dynamics
Mesh Generation
„ Discretization of the
complex arterial
lumen into
hexahedrons, whose
size and distribution
largely govern the
accuracy of the
computed velocity
field

Papafaklis MI. PhD Thesis 2008

 Computational Fluid Dynamics
Fluid properties & boundary conditions
„ Definition of fluid properties (blood)
„ Homogeneous Newtonian / non-Newtonian fluid
„ Density (ρ): 1050 kg/m3
„ Dynamic viscosity (μ): 0,0035 Pa·sec
„ Boundary conditions
„ Laminar flow
„ Steady (e.g. Q=1ml/sec) /Pulsatile flow
„ Velocity profile (flat / parabolic) at the inlet of the
artery
„ Non-slip condition at the arterial wall
„ Pressure condition at the outlet of the artery
 Computational Fluid Dynamics
Numerical Solution
„ Discretization of the
equations for each
control volume
(hexahedron)
„ Initial approximate
solution at each node of
the computational mesh
„ Continuous iterations of
the solution
„ Error minimization and
convergence to the
exact solution
 Computational Fluid Dynamics
Blood flow simulation

„ 3D lumen
reconstruction
and
blood particle
tracking in a
right coronary
artery

Papafaklis MI. PhD Thesis 2008

 Computational Fluid Dynamics
Blood flow simulation
„ Streamlines in a right coronary artery lumen

Papafaklis MI. PhD Thesis 2008

 Computational Fluid Dynamics
Blood flow simulation
„ Velocity profiles in lumen cross-sections

Papafaklis MI. PhD Thesis 2008

 Computational Fluid Dynamics
Blood flow simulation
„ 3D colour map of shear stress distribution
 Computational Fluid Dynamics
Blood flow simulation
„ “Angioscopic” view

Wahle et al. SPOIE Proceedings 2001

 CFD is a technological tool which in combination
with imaging modalities can accurately simulate the
hemodynamic environment in human arteries

Why do we need to
simulate blood
flow in the Because it
arteries ? is fancy ! ? !
 Hemodynamic forces &
Atherosclerosis
„ Chronic, inflammatory and fibroproliferative disease mainly of large-
and medium-sized arteries
„ Remains the leading cause of death in the developed world
„ Despite the systemic nature of its associated risk factors (i.e.
hypertension, smoking, hyperlipidemia, diabetes mellitus, social
stress), atherosclerosis is a site specific disease and its
manifestations are focal and eccentric
„ Specific regions are affected: branch points (outer edges of blood
vessel bifurcations) and the inner walls of curved arteries
„ Within each patient, each coronary obstruction progresses,
regresses, or remains quiescent in an independent manner
„ Local factors (hemodynamic forces) play a major role in the regional
localization of atherosclerosis
 Association of shear stress with
atherosclerosis
„ Low shear stress was first implicated in atherosclerosis
distribution ≈40 years ago Caro et al. Nature 1969
„ Correlation of low SS with localization of atherosclerosis
„ In vitro experiments with direct measurement of near wall
velocity gradient Friedman et al. Atherosclerosis 1981

„ Computational fluid dynamic (CFD) simulations in autopsy-based

arterial models Rindt et al. J Biomech 1990

„ In vivo experiments in animal models

Suo et al. Arterioscler Thromb Vasc Biol 2007

„ In vivo investigations in humans using 3D imaging techniques

(angiography, IVUS, MRI) and CFD
Pedersen et al. Eur J Vasc Endovasc Surg 1999
Krams et al. Arterioscler Thromb Vasc Biol 1997
 Hemodynamic forces &
Localization of atheromatic plaques
Association of low shear stress with
atherosclerosis
in coronary arterial segments

Van Langenhove et al. Circulation 2000

 Association of low shear stress with
atherosclerosis
in coronary arterial segments

„ Serial intracoronary study (3D anatomy and CFD) in

patients with stable angina revealed plaque progression
in areas with low shear stress
Stone et al. Eur Heart J 2007
 Association of low shear stress with
atherosclerosis
in left main coronary artery bifurcation
„ In vivo study using 3D
reconstruction and CFD
demonstrated an
association of disturbed
flow and low shear
stress with increased
plaque thickness
„ Plaque thickness was
found to be inversely
related to shear stress in
five patients

Papafaklis et al. Int J Cardiol 2007

Papafaklis et al. (abstr) Heart 2007
 Shear stress and
Vulnerable plaques
„ Low SS has been lately found in a serial IVUS study (coupled with
CFD analysis) in swines to be an independent predictor of plaque
location, development and progression to a high-risk plaque with:
„ Intense lipid accumulation
„ Inflammation Low SS
„ Thin fibrous cap
„ Internal elastic lamina fragmentation TCFA
Media thinning Excessive
„
Intense
Excessive expansive remodelling expansive
„ inflammation
remodelling

„ The magnitude of low SS at baseline was associated with the

severity of high-risk plaque characteristics
Chatzizisis et al. Circulation 2008
 Role of shear stress in
in-stent restenosis
Bare metal stents
„ Neointima thickness is inversely related to shear stress
Wentzel et al. Circulation 2001

„ Low shear stress areas

must be considered as
areas with a higher
probability for neointimal
hyperplasia to be present
and more prominent

Papafaklis et al. (abstr) J Am Coll Cardiol 2006

„ Adjunctive brachytherapy was found to reduce the effect of shear

stress on neointimal hyperplasia
„ Areas with sufficient irradiation and thus, minimal neointimal thickness
→ minimal effect of SS on in-stent restenosis because of brachytherapy
induced cell death Papafaklis et al. Int J Cardiol 2008
 Role of shear stress in
neointima distribution
Drug-eluting stents
„ Low shear stress is associated with neointimal hyperplasia
Gijsen et al. Am J Cardiol 2003
„ Shear stress does not seem to play a role in tissue regression and
lumen enlargement which occur after drug-eluting stent implantation

Papafaklis et al. (abstr)

J Am Coll Cardiol 2008
Papafaklis et al.
Heart Vessels 2007
 Clinical Implications
„ Detection of vulnerable plaques at an earlier stage by
adding CFD techniques to current imaging methods:
„ invasive (IVUS-based virtual histology and palpography,
thermography, intravascular MRI, angioscopy)
„ noninvasive (MSCT, MRI, PET)
„ Assess the vulnerability risk of a vessel or patient
„ Selective invasive treatment (use of stents to stabilize
high-risk plaques ? ? ?)
„ Limitation: vulnerable plaques are not single localized lesions
restricted to one coronary artery only
„ Prognosis of probable locations of restenosis after stent
implantation
 Conclusions
„ Low shear stress explains the focal susceptibility of the
arterial system to atherosclerosis and neointima
distribution following stent implantation

„ Incorporation of in vivo hemodynamic measurements by

using CFD in current diagnostic methods may increase
our knowledge on the pathobiology of coronary artery
disease with beneficial implications for the vulnerable
patient

„ Future: Create a prognostic model for vulnerable

plaques based on hemodynamic parameters
Thank you