Cardiac Disease Meets Its Match

As the human heart pumps, blood cells, platelets, and plasma course through the body’s snarled network of blood vessels. Over the years, the relentlessly high volume of traffic and the stress of millions of vessel-wall expansions take their toll. Arteries can harden and inflame as atherosclerotic plaques — piles of lipids, cell debris, and connective tissue — accumulate along the vessel walls.

But not all plaques are the same. A large plaque might sit placidly for years, with blood sliding around it, while a smaller, seemingly innocuous plaque may rupture, exposing cracks where blood clots can form, stopping blood flow and resulting in heart attack.

Current cross-disciplinary work between Boston University engineers and physicians may yield the technology needed to tell dangerous plaques from harmless plaques. 

“We don’t understand very well why some plaques cause heart attacks and some don’t, and we are definitely unable to predict which plaques will rupture before an event actually occurs, based on conventional risk factors,” says Frederick Ruberg, a School of Medicine assistant professor of medicine and radiology and codirector of the Advanced Cardiac Imaging Program at Boston Medical Center.

Ruberg is collaborating with Joyce Wong, a College of Engineering associate professor of biomedical engineering, and James Hamilton, a MED professor of biophysics and an ENG professor of bioengineering. The three are developing a tactic that uses targeted molecules and magnetic resonance imaging (MRI) to accurately identify dangerous plaques.

Wong, postdoctoral researcher Kristen LaFlamme, and undergraduate Alexander Razon (ENG’10) make particles of iron oxide approximately 5 to 10 nanometers in diameter that can seek and attach selectively to the dangerous plaques, based on specific molecular “tethers” on the particles. An MRI scan then reveals the particles’ location, as dark dots clustered at the surface of high-risk plaques.

“To have something like this with a very clear end point could become a test bed for clinical trials,” says Wong. “We already have a particle you can see in magnetic resonance. It’s a matter of fine-tuning it.”

“The standard technique to look at plaques in blood vessels just gives data on quantity or how tight the blockage is and doesn’t give information about the plaque makeup,” says Hamilton, who directs the High Field Imaging Center at MED. In conjunction with other tests, detecting the composition of plaques would help doctors pinpoint dangerous plaques early and treat them aggressively.

The project is funded through the Translational Research Partnership between the University and the Wallace H. Coulter Foundation, which supports several one-year research projects aiming to improve patient care through collaboration between biomedical engineers and clinicians. The Center for Nanoscience and Nanobiotechnology also supported some of this work, as part of the Center’s effort in advancing the field of nanomedicine. Wong is the Associate Director of the Center.

With their Coulter award, Ruberg, Wong, and Hamilton will work on selecting tether molecules to coat the particles that can most accurately point out dangerous plaques. They will also conduct toxicity studies, making sure the plaque-finding particles will not disrupt normal functions when injected into the bloodstream.

“The common goal is to detect vulnerable plaques, and we all come at it from different angles,” says Wong. “The project wouldn’t succeed with just one of us. We need all three aspects to make it work.” 

This article originally appeared in the fall issue of the BU College of Engineering magazine. Click here to read past issues.