Prosthetic heart valves are routinely used for replacing diseased heart
valves. However, thromboembolism in mechanical valves, and durability
in Bioprosthetic ones remain as obstacles to these devices. It
is well known that flow induced thrombogenicity, by chronic platelet
activation, is the prominent aspect of this blood trauma. It has also
been previously shown that patients with cardiac valve replacement, regardless
of type of the valve, had increased plasma fibrinogen, plasma viscosity
and platelet aggregation compared with normal subjects. Although, this
problem is much more pronounced in patients with mechanical prostheses
who need a life-long anticoagulant therapy, patients with bioprostheses
are also at low risk of thrombogenesis in short period after surgery
so that anticoagulants are usually needed for a limited period.
Fluid
mechanical factors involved in platelet activation and aggregation
include high shear rates, turbulence, and areas of flow stagnation or
recirculation that are characterized by low shear and longer residence
time. These factors are crucial in using a heart valve and must be considered
in design or modification of these devices.
Cardiovascular
and Biofluid laboratory at Caltech is one of frontiers in designing
and testing heart valves nationwide. In collaboration with heart valve
industries, different types of valve prototype (mechanical, porcine,
polyurethane and pericardial) have been mechanically analyzed, tested
and designed.
In the field of cardiology, our current ability to accurately
detect diastolic dysfunction is unsatisfactory due to the lack
of an effective diagnostic index. Conventional measurements
that reflect changes in normal diastolic function generally depend
on patient-specific indices like
the onset, rate, and extent of ventricular
filling and pressure decline;
pressure-volume or stress-strain
relationships during diastole;
and relations between E and A waves
in Doppler echo.
In fact, ultrasonic measurements of existing blood
flow indices cannot be interpreted correctly without a prior knowledge
of gender, heart size, etc. Another difficulty lies in the occurrence
of pseudonormalization, which prohibits further deterioration
of diastolic function from appearing in E/A ratio changes. Moreover, these
conventional indices usually do not show a significant change
until the heart is seriously dysfunctional and therefore,
their effectiveness is limited.
Objective
The general objective of this research project at Caltech is to develop
a better understanding of the role of trans-mitral blood flow in
healthy hearts and in congestive heart failure (CHF). A more specific
objective is to characterize this role by developing physical correlations
between hemodynamic factors defining trans-mitral flow and diastolic
function in early diastole. The presence of vortical structures
that develop along with a strong propulsive jet during normal diastole
has been confirmed previously by analyses based on color Doppler
mapping and Magnetic Resonance Imaging. Thus, physical characteristics
of these vortical structures may provide more effective indices
of diastolic function than existing methods.
Vortex Ring Formation
Process of formation of a vortex ring in fluid mechanics literature
is described by a dimensionless number called formation time. The
importance of this number lies in the fact that by increasing it
beyond a certain range (~3.5-4.5) for a starting jet, no additional
energy or circulation enters the leading vortex ring, and the remaining
fluid in the pulse ejects as a trailing jet. The critical role
of the vortex ring formation rests on the relative contribution
of the leading vortex ring and the trailing jet (which appears
after pinch off) to the thrust supplied to the flow.
Images (click on images below to
see larger image)
Computational Investigation of the Effects of Heart
Rate Variation on Renal Blood Flow: One of the critical effects
of congestive heart failure (CHF) is reduced blood flow through
the descending aorta due to mild to severe reduction of cardiac
output (CO). This decrease in blood flow, combined with increased
heart rate (HR) in CHF patients, can result in retrograde flow
and negative shear stress along the vessel walls in each cardiac
cycle. Moreover, it has been observed that kidneys could malfunction
in cases of CHF and also after certain athletic activities. In
our study, we hypothesize that this may be caused by a decrease
in blood flow supplied to the vasculature and kidneys at high
HR. Such hemodynamic conditions can lead to the amplification of
retrograde flow and negative wall shear stress; a reduction in
endothelial nitric oxide production along the vessel walls during
each cardiac cycle; and consequently vasoconstriction at the renal
bifurcation region. In order to evaluate the role of wave reflection,
Womersley number, flow waveforms, arterial diameter, and elasticity
on the magnitude and duration of the wall shear stress in the renal
bifurcation, A 3D numerical simulation of the flow in the renal
bifurcation and the descending aorta was performed. the simulation
used the commercial finite element package ADINA (ADINA R&D,
inc., MA). The result imply that pressure wave reflection from
the downstream arterial bed back into the main aortic branch, have
a significant impact on the flow in the suprarenal region and
thus on the presence of retrograde WSS.
Congenital heart defects remain the most common birth defect
in humans, occurring in over 1% of live births. The high prevalence
of cardiac malformations can be partially attributed to limited
knowledge regarding the embryonic roots of the disease. A variety
of congenital heart defects are thought to arise from combinations
of genetic and epigenetic factors. In an effort to better understand
this dynamic relationship, we are exploring the structure and function
of the developing heart and valves to identify epigenetic factors
influencing heart development (Link to Movie 1
[17 MB] from Nature). In order to study cardiac mechanics,
we have employed novel high-speed line scanning confocal microscopy
and four-dimensional visualization techniques. A dynamic four-dimensional
dataset showing heart development along with blood flow patterns
throughout cardiac morphogenesis has been assembled (Link to Movies
2 [291
MB],
3 [323
MB] ,
4 [19
MB] ).
Utilizing newly developed tools, we proposed a novel pumping mechanism
in the valveless embryonic heart tube via elastic wave propagation
and reflection (Link to Movies 5
[73 MB] ,
6 [24
MB] ).
We are currently studying how this pumping mechanism leads to flow
patterns that help guide later stages of cardiac development.
Movie Legends:
Movie 1
From (Hove et al, Nature, 2003); Bodipy-cermaide
stained 4.5 dpf zebrafish embryo acquired at 1.5 Hz
17 MB
Movie 2
Zebrafish heart development in Tg(gata1::GFP) embryos.
Blood cells are fluorescently labeled. (Fish courtesy of
Shuo Lin, UCLA)
291 MB
Movie 3
Zebrafish heart development in Tg(cmlc2::GFP) embryos.
Myocardial cells are fluorescently labeled. (Fish courtesy
of H.J. Tsai, NTU)
The impedance pump is low power, highly efficient and very simple
to manufacture and therefore is well suited to operate as a basic
fluid driving system in many biomedical applications on both the
macro and micro scales. However to further design efforts a better
understanding of the complex wave dynamics which enable the function
of the impedance pump was necessary. A comprehensive study of the
fluid and structural dynamics was therefore conducted using numerical
simulations which included an investigation of the various parameters
which influence the outflow rate and pressure wave dynamics in
the elastic tube as well as how these factors contribute to the
resonant nature of the impedance pump mechanism.
These results were then used to examine the function
of the impedance pump in the following biomedical applications:
on a coronary artery bypass graft (CABG) to improve anastomosis
hemodynamics
Enhanced pinching amplitude using gelatin layer in a Multilayered
Impedance Pump configuration especially suited for small pinching
amplitudes, as in intra aortic pump
In microchannels excited by piezoelectric pincher.
On a cavopulmunary conduit for improvement pressure regime
in the fontan procedure for children with HLHS.
To increase of heart efficiency by impedance pumping through
exploiting the natural properties of the aorta.
The research includes numerical simulations of axisymmetric and
physiological-based 3D models with flexible walls. The commercial
finite elements software ADINA (ADINA R&D inc.) was used to
incorporate the dynamics of the elastic tube, the contact between
the pinchers and the tube, the fluid dynamics and the fluid-structure
coupling at the interface. A direct coupling is used for the FSI
between the flow and the tube and the ALE approach is used to adjust
the mesh to the moving boundaries. These studies also analyzed
the relationship between pressure and flow and the energy regime
along the tube under different physiological pumping conditions.
The numerical models were then validated with experiments for specific
cases.
Multilayer Impedance
Pump (Please click on
the images, below, for viewing at a larger size.)
The
collaborative investigation by the Gharib and Fraser groups
on zebrafish cardiogenesis was able to show definitively that
the embryonic heart is a dynamic impedance pump that functions
throughout morphogenesis however one question which still remained
was how the zebrafish heart in its primitive state was able
to generate waves of amplitudes much greater than are possible
through simple myocyte contraction (~20%). At these early
developmental stages anatomical studies of the heart tube have
shown that majority of the tube is made out of a gelatinous
material, the cardiac jelly, and consequently is the only media
present to amplify the contractions of cardiac myocytes. using
the impedance pumping mechanism.
This problem is particularly relevant to the design of biomedical
devices where the actuators required at both small and large
scales are forced to take up a majority of the space in the
device to provide the displacement and bandwidth required to
operate them. Nature’s implementation of the gelatinous
amplification provided by the cardiac jelly circumvents this
mechanical limitation of both biological and man-made actuators.
Applying these concepts, the Gharib group has designed a Multilayer
Impedance Pump (MIP) which similar to the developing heart
tube includes a thick gel-like inner layer. Pumping is achieved
using the impedance pumping mechanism based on the constructive
interaction of elastic waves that are generated at a unique
asymmetrical excitation and that are reflected at the elastic
tube's extremities where a mismatch of impedance is present.
The MIP is especially suited for bio-medical applications
where space is often limited since small amplitude excitations
are all that are required to produce significant pumping. By
making the outermost layer rigid relative to the inner layers
all large wall motion is constrained to the inside of the pump.
Therefore the MIP is very suitable for cardio-vascular applications
such as a fully implantable intra-aortic pump. Similarly, a
smaller version of this device could also be combined with
a graft to enhance the device patency by preserving physiological
flow conditions. The following video shows a numerical simulation
of the pump displaying the flow (axial velocity vector plot)
inside the tubular multilayer tube when excited by periodic
compressions of small amplitude (solved using Adina®).
In this project we study the combination of geometrical
arrangements of muscle with its dynamic behaviour during contractions.
In this we are pursuing two geometrical models. The first is a
simple spiral wound about a tube, with varying degrees of inclination.
The second is the Torrent-Guasp model of the human heart. These
models allow us to study such things as heart function for healthy
and diseased hearts. We also pursue an understanding of heart development
through these models.
DENSE MRI is a new phase contrast method that provides
a 3D Lagrangian frame work for analysis of myocardial deformation.
In contrast with MR Tagging, which is affected by tag fading and
provides only the in-plane Lagrangian displacement, DENSE has a
higher spatial and temporal resolution (almost 1 mm and 10 ms respectively)
and is able to image the entire cardiac cycle. However, DENSE is
time consuming and therefore the full potential of this novel method
has not been revealed. Some of efforts we have done in this field
are as below:
combination of Short Axis (S.A) and Long Axis (L.A) images
that provides a more comprehensive data from DENSE MRI in 20
to 40% shorter time. <SA_LA.jpg>
demonstration of the sequential initiation of myocardial strain
as well as heterogeneous contraction patterns across the ventricle
wall based on a single slice long axis DENSE MRI of a beagle
heart for the whole cardiac cycle. <Media:Example.ogg>
measurement of mechanical deformations in the cardiac wall
through parameters like torsion along the long axis, thickening
and shortening indices, principal strain and total deformation
values.
Just to appreciate the potentials of the DENSE MRI look how the
particle tracking covers the atrium as well as the ventricle: <Media:Example.ogg>
Completed
Projects
Methods
to Evaluate Polymer Actuator Applications
Helical
Pump
Anna Hickerson
Sometimes when
I skip or hop or when I'm jumping suddenly I like to stop
and listen to my heart thumping. —Lilian Moore
