WPI team receives $1.8 million to study atherosclerotic plaque progression and rupture

The study will examine in unprecedented detail the physical and biological properties of atherosclerotic plaque, which is closely related to most cardiovascular disease, and point the way to new tools for predicting the likelihood of plaque rupture

WORCESTER, Mass. A research team led by Dalin Tang, professor of mathematical sciences and biomedical engineering at Worcester Polytechnic Institute (WPI), has received a five-year, $1.8 million award from the National Science Foundation to conduct a comprehensive study of the growth, progression, and rupture of human atherosclerotic plaque, a medical condition that is closely related to most cardiovascular diseases, including stroke and heart attack. Cardiovascular disease is the leading cause of death in the developed world.

With the NSF funding, awarded jointly by the agency's Division of Mathematical Sciences, the Directorate of Biological Sciences, and the National Institute of General Medical Sciences to support research in the area of mathematical biology, Tang and his team will use a combination of computational modeling, MRI (magnetic resonance imaging) scans of volunteer patients, and histological studies of diseased arteries to develop, for the first time, a detailed picture of the physical and biological conditions inside arteries that promote the initial formation of a plaque, and then favor its continued growth. The work will also reveal, in unprecedented detail, the factors that cause plaques to rupture, leading directly to heart attacks and stroke.

Plaques are deposits of fatty substances, cholesterol, calcium, fibrin (a protein that helps blood clot), and other materials. As they grow, they cause a narrowing of the artery (or stenosis) that can starve tissue downstream of oxygen and energy. Plaques can also rupture, spilling their contents into the bloodstream. Typically, a blood clot quickly forms on the site of a ruptured plaque, growing until it blocks the artery. When such a blockage occurs in an artery leading to the heart, it is called a myocardial infarction, or heart attack. The blockage of a carotid artery leading to the brain is called a stroke.

In addition to Tang, the principal investigators include two other WPI mathematicians, Joseph D. Petruccelli and Homer F. Walker, both professors of mathematical sciences, and Chun Yuan, professor of radiology, bioengineering, and electrical engineering at the University of Washington School of Medicine. The team also includes researchers at the University of California, Irvine, Shinshu University in Nagano, Japan, and Beijing Normal University in the People's Republic of China.

The new research will build on work conducted by Tang over the past 14 years with support from the NSF, the Whitaker Foundation, and the National Institutes of Health/ National Institute of Biomedical Imaging and Bioengineering. In previous studies, Tang has studied blood flow in arteries partially blocked by plaque, measured the stress and strain conditions that may lead to the plaque rupture, and determined--contrary to what most researchers had believed--that localized maximal stress conditions within a plaque, rather than the maximum stress within an artery at the site of the plaque, is the most accurate indicator of how likely the plaque is to rupture.

The current study will extend this work by developing a better understanding of why and how plaques form, and detailing the sequence of events that ultimately trigger catastrophic plaque rupture. MRI and histological studies of diseased arteries will be used to document the progression of plaques and assess their likelihood of rupture. For the first time, human plaque growth functions will be quantified based on multi-year patient-tracking data. This information will become the basis for sophisticated three-dimensional computer models that will enable the researchers to explore the complex interactions of blood flow, artery shape, and plaque structure to determine which conditions promote plaque growth, why some plaques remain stable, and why others fail.

The ultimate goal of the ongoing work is to develop better diagnostic tools for physicians to help them assess the risk that patients face from arterial plaques and choose the best course of treatment--from changes in diet and lifestyle, to surgical intervention, which is generally reserved for the most severe risk. These tools will likely include computational methods, technology, and software that can be added to MRI and ultrasound scanners to measure the structure of plaques and their internal stresses, and derive an index of their likelihood of rupture.

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About Worcester Polytechnic Institute

Founded in 1865 in Worcester, Mass., WPI was one of the first engineering and technology universities in the nation. WPI's 18 academic departments offer more than 50 undergraduate and graduate degree programs in science, engineering, technology, management, the social sciences, and the humanities and arts, leading to the B.S., M.S., M.E., MBA and Ph.D. WPI's world-class faculty work with students in a number of cutting-edge research areas, leading to breakthroughs and innovations in such fields as biotechnology, fuel cells, nanotechnology, and information security. Students also have the opportunity to make a difference to communities and organizations around the world through our innovative Global Perspectives program. There are over 20 WPI project centers throughout North America and Central America, Africa, Australia, Asia, and Europe.


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