Examining plaques in coronary arteries

Macrophages guard the body against pathogens, yet they also can accelerate cardiovascular problems by weakening the fibrous cap surrounding artery-blocking plaques and promoting dangerous blood clot formation after they rupture.

Because MRI and PET reveal such macrophage-rich structures with limited success in the coronary arteries, finding a more effective imaging method could enable potentially life-saving early identification.

In the April 8 online issue of Nature Medicine, Dr. Zahi A. Fayad and his colleagues at Mount Sinai School of Medicine in New York, along with researchers from Bichat Hospital in Paris and from New York University School of Medicine, report their use of CT imaging with an iodinated nanoparticle-based contrast agent from NanoScan Imaging of Lansdale, Pa., dubbed N1177, to image macrophages in a rabbit model.

An artery-blocking plaque becomes clearly visible in CT images two hours after injection of an iodinated nanoparticulate contrast agent (left). A conventional contrast agent yields significantly lower enhancement (right). Reprinted with permission of Nature Medicine.

The scientists used optical microscopy and mass spectroscopy to show that macrophages took up the agent in vitro. A conventional CT agent was poorly absorbed, by comparison.

CT imaging of atherosclerotic rabbits with a Siemens Medical Solutions 64-slice multidetector scanner revealed that the nanoparticulate agent accumulated at peak levels in naturally macrophage-rich organs two hours after its injection. Insignificant levels of it were found in the aorta’s walls and in other structures at this point. No uptake was observed in healthy rabbits.

Compared with the conventional agent, the experimental agent produced significantly higher enhancement of plaques in diseased animals. Analysis of their tissues verified the relationship between the agent’s uptake and higher x-ray absorption. Based on these results, the technique can be used to selectively image high-risk plaques.

The researchers emphasize that future studies will have to determine the optimal dose and kinetics of the compound. Additionally — unlike MRI — the technique could place a significant radiation burden on patients. However, because it yields high-resolution images, does not require injection of a radioactive tracer (as with PET) and is faster than MRI-based techniques, CT imaging with the agent may aid investigation of coronary artery clogging as well as of infectious and autoimmune diseases.