Photoacoustic Imaging Technique Detects Arterial Plaques

Researchers at Michigan State University (MSU) used light-activated nanoparticles and photoimaging to locate and image cells found in the arteries, cells that could lead to heart attacks and strokes.

MSU professor Bryan Smith and his team worked with researchers from Emory and Stanford universities to develop nanoparticles made from carbon (i.e., carbon nanotubes) that selectively target the types of immune cells that are abundant in inflammatory plaques. Though it is difficult to prove whether a particular plaque is responsible for a stroke or heart attack, the prevailing belief is that vulnerable plaques are the most dangerous, Smith said. These are inflammatory plaques that can rupture and consequently block blood vessels.

A new imaging technique uses nanoparticles to help reveal vulnerable plaques in arteries that can lead to strokes and heart attacks. Immune cells in the plaque attract the nanoparticles, which can then emit a signal that’s seen in red in the image on the right, taken from a mouse artery. That signal is absent — meaning a plaque goes undetected — in the artery on the left, which shows a mouse that did not receive the nanoparticles. Courtesy of Advanced Functional Materials.

The researchers injected the light-sensitive nanoparticles into a mouse model that mimicked human inflammatory plaques histopathologically. When the researchers shined laser light into the arteries of the model, the nanoparticles absorbed the light and emitted sound waves when plaque was present. The researchers used this acoustic signal to locate and visualize the plaque.

“The power of our new technique is in its selectivity,” Smith said. “There are certainly other methods to image plaques, but what distinguishes this strategy is that it’s cellular. We’re specifically looking at the cells — called macrophages and monocytes — that are most responsible for making a plaque vulnerable in the first place.”

Single-cell flow cytometry performed within the plaques revealed that the nanoparticles were almost exclusively absorbed by the inflamed immune cells that infiltrate plaques.

“If you look at a normal blood vessel versus one with a plaque, there’re a lot more macrophages and monocytes in the one with the plaque,” Smith said. “And our method is really looking at the monocytes and macrophages. Virtually no other cell type takes up the nanoparticles.”

Using photoacoustic imaging, the researchers identified inflamed atherosclerotic plaques that displayed an approximately sixfold greater signal compared to the controls — six hours after the mice were injected with the carbon nanotubes.

This approach could offer a targeted, noninvasive way to accurately identify and diagnose inflamed atherosclerotic lesions.

“Currently, there is no effective way to accurately locate and treat vulnerable plaques before they lead to a heart attack or stroke,” Emory University professor Eliver Ghosn said. “We hope our studies will help change that.”

From a treatment standpoint, Smith’s lab also showed that the nanoparticles can be loaded with a drug for fighting plaques. The team will also explore how to use the nanoparticles to aid with imaging as well as delivering a therapeutic.

The research was published in Advanced Functional Materials (www.doi.org/10.1002/adfm.202101005).