Duke biomedical engineers have received more than $2.2 million from the
National Institutes of Health (NIH) to continue their explorations of how
the complex moving and flexing of blood vessels during a heartbeat might
contribute to heart disease.
They are combining clinical images of beating hearts and computer software
to perform challenging visualization studies of the coronary arteries that
supply the heart with blood. Their goal is to determine whether there
are certain motions that predispose vessel walls to thicken and ultimately
reduce blood flow, or to develop a clot that blocks the vessel entirely.
At each beat a heart's blood vessels, which are embedded in its surface,
alternately stretch and contract, with some vessel segments bending or
twisting in the process. All those push-pull, twist-turn motions
substantially change the mechanics and chemistry of the arteries in ways
that are not completely known, say the engineers.
Such conformational changes, if they could be thoroughly understood, would
provide doctors with a new set of "geometric risk factors" that might
predict the early onset of atherosclerosis. Atherosclerosis is the
development of restrictions and blockages in arteries that can lead to heart
"We're trying to understand the development and origins of the disease,"
said Morton Friedman, a biomedical engineering professor who leads the
Cardiovascular Simulations Laboratory at Duke's Pratt School of Engineering.
"We're also trying to identify people who might be predisposed to it. If we
can understand why it happens, that may help us find ways to stop it or slow
down its progress.
"The traditional risk factors for cardiovascular disease -- high
cholesterol, high blood pressure, smoking, diabetes, obesity - only explain
about 50 percent of the disease's incidence. So other factors must be
involved," said Friedman.
While other research teams have probed living vessels of the heart for ties
to heart disease, "I think the focus on dynamic geometry is pretty much
ours," Friedman said.
Friedman was already searching for such geometric risk factors in cardiac
vessels when he came to Duke in 2001 from The Ohio State University.
Transferring with him were Hui Zhu, now a Duke assistant research professor
of biomedical engineering, and Yun Liang, now among Friedman's graduate
students at Pratt.
Zhu, whose training is in electrical engineering, is an expert in getting
the most out of the images provided by two technologies used to visualize
the interiors of blood vessels in live, beating hearts.
The first technique, called biplane cineangiography, uses X-rays and an
injected dye to create a kind of two-dimensional moving picture of blood
flowing inside vessels. The second method, intravascular ultrasound, enables
researchers to visualize the wall thicknesses of those vessels, as well as
providing some idea of what the walls are made of.
Liang, meanwhile, is enhancing the ultrasound information by extending it to
the third dimension. And Zhu is also an expert at statistically analyzing
images to determine whether certain vessel geometries can be linked to
indications of early atherosclerosis.
In an article in the December, 2003 issue of the research journal
Arteriosclerosis, Thrombosis and Vascular Biology, Friedman and Zhu
described their use of all these tools to find statistical links between the
thickness of vessel walls and how the arteries curve and twist during a
"These thickness variables are of particular interest, because wall
thickening is an important part of the atherosclerotic process," the two
Duke researchers wrote.
In the early stages of a developing blockage, the wall of a diseased
coronary artery "actually grows outward to maintain the opening," Friedman
explained in an interview. "But eventually that so-called compensatory
enlargement becomes insufficient."
The growth of such obstructions is a complex process, he said. First, fatty
materials called lipids enter the wall from the blood. Those deposits induce
an "inflammatory response" by blood cells that collect and die in the same
place. Other cells then accumulate there too. These accumulations form the
deposits called plaque, which Friedman described as "a whole mishmash of
fibrous materials, lipids, dead cells, calcium and cholesterol crystals."
In some cases, the end result is a plug that fills most of the vessel
opening known as the lumen. But "in most cases that lead to heart attack
that's not what happens," he added. "In most of those cases the plaque is
fragile. As a result it ruptures. And in breaking it exposes all this junk
to the blood. Then a clot forms that actually blocks the vessel."
Friedman noted that certain enzymes attack plaque, making it weaker and more
vulnerable to rupturing. "It could be that the flexing of vessels as the
heart beats could have a role in deciding which plaques are more likely to
rupture," he said. "If we got to the point where we really could understand
what is going on, perhaps we could identify people whose arterial dynamics
or geometry put them at greater risk."
Under their newly funded four-year NIH research, Friedman's team will
investigate the validity of several hypotheses with collaborators at Duke
Medical Center, Vanderbilt and Texas A&M universities and the University
of Texas/Southwestern Medical Center.
One hypothesis holds that "the local geometry and motion" of disease-prone
vessel segments "has a significant influence on the initiation, progression
and stability" of atherosclerosis. Another proposes that "different features
of artery geometry and motion play influential roles at different stages in
the development of coronary artery disease."
The Duke team will apply its visualization and analytical techniques to
cineangiogram and intravascular ultrasound images of living human patients
provided by several of their collaborators.
Only some of those scanned vessels will be diseased, Friedman stressed. "In
addition to the diseased cases, we are developing a catalog of coronary
artery motion on the normal human heart so we can start to identify what is
normal and what is not," he said.
To do detailed studies that would be inappropriate in living human patients,
the engineers will also apply these techniques to laboratory mice that have
been genetically modified to predispose the animals to developing
"Over a reasonably short period of time we can get lesions in the mice that
look a lot like human lesions," Friedman said. "Their coronary anatomy is