In conventional imaging, stable and dangerous lesions have a similar appearance. But new techniques using contrast-enhanced high-resolution MR molecular imaging can help to determine when to treat atherosclerotic plaques and when to leave them alone, according to a Saturday minicourse on molecular imaging.
"Doctors need to distinguish between stable lesions and unstable ones that have the potential to rupture," said Dr. Emmanuelle Canet Soulas, physiologist and MRI researcher at the University Hospital of Lyon in France. "In cases of atherosclerosis, the leading cause of mortality in Western countries, vascular wall disease needs to be characterized for prompt and appropriate action."
Due to its multicomponent composition, plaque is a tricky pathology to image, sometimes moving from fatty streak to complex plaque in a single lesion and needing multicontrast MRI characterization and a 3D approach to study the spatial progression of disease.
"The biologist needs to identify exactly what's going on in terms of the plaque's chemical content, such as the presence of macrophages or lymphocytes, a thin fibrous cap, and likelihood of apoptosis," Canet Soulas said.
Multiple cellular targets, such as macrophages, smooth muscle cells, and T-lymphocytes, as well as such molecular targets as inflammation, thrombus, enzymes, and receptors, require a strategy involving multiple agents that bind to the specific components.
The next step will be for a pharmaceutical study in mice of MR-specific probes in the aortic arch and the carotids. It could be another five to 10 years before targeted molecular imaging clinical trials are initiated in humans, she said.
Annexin A5, a protein that binds to all dominant features of vulnerable plaques including apoptosis, inflammation, and intraplaque rupture, may provide an ideal targeting agent for the detection of atherosclerotic plaque instability, according to Dr. Leonard Hofstra, a cardiologist at the University Hospital of Maastricht in the Netherlands. Increasing uptake of the protein is associated with plaque instability. Hofstra hopes that the binding abilities of Annexin can be applied to other diseases.
"Agent uptake could be predictive of conditions such as heart failure and scar formation, but larger studies are needed," he said.
Hofstra added that molecular imaging is pivotal in the development of drug targeting.
"Targeted agents could also be loaded with drugs that kill tumor cells and act like biological cruise missiles," he said.
Such targeting could result in better cancer treatment with fewer side effects. While improved therapy is an important aspect of such innovative techniques, doctors are keen to underline the advantages of this relatively noninvasive tool for early detection.
Mantra-style, Hofstra reiterated the last line of his opening Chinese proverb: superior doctors prevent the disease.
