Researchers have developed a new medical imaging marker designed to specifically target and illuminate areas of cholesterol buildup. The marker provides clear images of cholesterol plaques from within blood vessels and could one day help prevent heart attacks and other cardiac events.
Watching cholesterol: Researchers have designed a new imaging molecule detectable by MRI that can highlight cholesterol buildup in blood vessels. The molecule mimics the shape of high-density lipoprotein (HDL) and is composed of an outer phospholipid layer (orange, blue, and red dots) surrounding a layer of peptides (spirals).
“None of the technology we have looks directly at what’s happening in vessels, and two-thirds of heart attacks occur in vessels,” says Zahi Fayad, a professor of medicine and radiology at Mount Sinai who led the research.
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Today, cardiologists use a variety of tools to examine the heart. MRI and CT scans provide noninvasive images of the extent of plaque buildup in blood vessels, although they can’t distinguish the most problematic types of plaques. But cardiologists lack a noninvasive way to get a detailed picture of plaque.
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“The real danger of heart attacks comes from the rupture of unstable plaque, not necessarily thick plaque,” says David Cormode, a postdoctoral researcher at Mount Sinai who helped design the contrast agent. “Unstable plaques are extremely thin and difficult to image in detail.”
Directly labeling the plaque inside blood vessels with a marker that can be detected by MRI, known as a contrast agent, could provide a better picture. But getting these molecules across the vessel lining has been a challenge. New research shows that contrast agents that mimic a natural molecule–high-density lipoprotein (HDL), or “good” cholesterol–could do the trick. Normally, HDL passes through arteries and attaches to low-density lipoprotein (LDL), or “bad” cholesterol, carrying it out of arteries to the liver.
Fayad and his colleagues designed a synthetic version of HDL and added gadolinium, a standard chemical that is detectable by MRI. They injected the labeling molecule into the tail veins of mice with and without cholesterol buildup. After 24 hours, they observed a 79 percent increase in the detection of cholesterol in mice with plaque buildup compared with images taken the day before, according to research presented at the national meeting of the American Chemical Society last month. Areas with greater plaque buildup appeared brighter. The researchers saw no change in mouse controls.
“It’s like a smart bomb that goes directly to the plaque,” says Fayad. “We were able to see plaque in high contrast.”
In their images, the team also detected accumulations of macrophages–killer cells that invade areas of injury or inflammation such as plaque buildup. These macrophages secrete enzymes that Fayad says “eat up” plaque, making it unstable and more likely to rupture, which in turn could lead to heart attacks. Being able to detect these cells early on could help identify people at high risk of heart disease, as well as help develop treatments and lifestyle changes before their condition worsens.
Next, the team plans to test the HDL-based contrast agent on rabbits and pigs. Before they test on humans, Fayad says they will have to test where the agent travels in the body, as well as any toxic potential it may have.
“It is a significant step forward, but many questions remain,” says Thomas Grist, professor of magnetic resonance imaging at the University of Wisconsin-Madison School of Medicine. For example, it’s not yet clear if the molecule specifically labels unstable plaques, he says. Further studies comparing mice with stable versus unstable plaque may help confirm the group’s initial findings.
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Cormode anticipates that the technique will be available for clinical use in the next five years. “We have many people die of heart attacks per day,” he says. “And we really need some additional diagnostic information to reduce the level of death we’ve seen from this.”
