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WORCESTER, Mass. A Worcester Polytechnic Institute (WPI) research team has received a four-year, $1.4 million award from the National Institutes of Health (NIH) to continue a groundbreaking study of arterial plaque. This research could lead to tools that will enable physicians to predict the likelihood of plaque rupture, which is responsible for most heart attacks and strokes. Led by Dalin Tang, PhD, professor of mathematical sciences and biomedical engineering at WPI, the team is collaborating with researchers at Washington University in St. Louis and the University of Washington in Seattle on the research, which combines sophisticated computer modeling with an array of diagnostic technologies to more accurately chart the development of atherosclerotic plaque (fatty deposits) in the coronary arteries.

Arterial plaques are complex structures made up of cholesterol and other fats, calcium, fibrin (a protein that helps blood clot), and other materials. When they reach an advanced stage, plaques may develop a thin, membranous or fibrous cap. When this is torn open, it releases the contents of the plaque into the bloodstream. Plaque rupture causes some 60 percent of sudden, unexpected heart attacks. While the link between plaque build-up and cardiovascular disease has long been recognized, the factors that cause plaques to form, grow and rupture have been less clearly understood.

Better understanding the evolution of arterial plaque is important, Tang says, given the central role it plays in cardiovascular disease. As plaque deposits grow they cause a narrowing of arteries (called stenosis), which diminishes the amount of oxygen and nutrients blood can carry to the body and puts increasing stress on the heart. When plaques rupture, a blood clot (thrombosis) typically forms at the site and may block the artery. Such a blockage in a coronary artery leading to the heart is called a myocardial infarction or a heart attack. A similar blockage of the carotid artery leading to the brain is a stroke.

Tang and his team are arguably the leading research group studying how plaque components, fluid forces and structural forces, collectively, conspire to cause plaque rupture. Using computational models, magnetic resonance imaging (MRI) scans of volunteers, and histological studies of diseased arteries, they have spent several years investigating mechanisms governing plaque progression and factors and indices that could be used to predict potential plaque rupture. Tang published the first paper about this multi-component plaque model in 2004.

The new NIH award will enable the team to extend this research. Combining such techniques as patient-specific, image-based computational modeling, intravascular ultrasound (IVUS), angiography, MRI, and mechanical testing to analyze atherosclerotic coronary plaques, the team aims to zero in on what factors--including the forces from blood flow, pressure, and heart motions--best assess quantitatively which of those plaques are most likely to rupture.

Since 60 percent of all heart attacks and strokes are caused by such ruptures and occur without advanced notice, doctors err on the side of caution and may recommend more surgical remedies than are actually necessary, Tang says. In fact, he notes, only one out of 20 carotid endarterectomies (removal of plaque from an artery) currently performed is likely necessary (in other words, only one plaque would actually rupture).

Currently, the trigger for these surgeries is a high level of arterial stenosis. However, with better diagnostic approaches, the trigger might, instead, be identification of arterial plaque with a high potential to rupture, with plaque morphology, tissue components, and mechanical forces all taken into consideration. By developing better diagnostic tools, Tang and his team hopes to improve plaque assessment techniques for early diagnosis, treatment and prevention of cardiovascular disease.

In addition to Tang, WPI co-investigators on the grant are Kristen L. Billiar, associate professor of bioengineering and tissue engineering, and Joseph Petruccelli, professors of statistics. Jie Zheng, assistant professor of radiology at Washington University's Mallinckrodt Institute of Radiology, is principal investigator at WU. Roger Kamm, Germeshausen professor of mechanical engineering and biological engineering at MIT is a consultant on the grant.


Contact: Michael Dorsey
Worcester Polytechnic Institute

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