Coronary artery disease is a leading cause of death for both men and women, but right now, about half of men and almost two-thirds of women with this condition show no symptoms before experiencing a heart attack. Moreover, screening tests-from simple blood tests to invasive angiograms-commonly fail to detect signs of pending trouble. The urgent need exists for a better diagnostic test.
Researchers at Mount Sinai Heart are meeting that need, in the form of an advanced type of magnetic resonance imaging (MRI) that is capable of pinpointing potential hazards long before people develop symptoms of atherosclerosis (the buildup of fat deposits in the blood vessels). Known as black-blood MRI, the technique provides the most detailed images yet recorded of the walls and main channels of coronary arteries in living humans.
"This is a significant advance in methodology," says Valentin Fuster, M.D., Ph.D. "Black Blood MRI may allow vulnerable/high-risk artery plaques to be identified well before they rupture and may also provide a way to target treatment to prevent a heart attack." Unlike x-ray angiography, the current gold standard for assessing arteries, MRI is noninvasive and does not require catheterization, radiation, or potentially toxic intravenous contrast material.
The quest for a better diagnostic method began more than 12 years ago when Dr. Fuster and his colleagues discovered that many heart attacks were occurring in patients in whom angiography had failed to find significant blockages. Either the test was missing something or cardiologists were looking in the wrong place. A little of both, it turns out, is true.
"The angiogram measures only how clogged the vessel is," says Zahi A. Fayad, Ph.D., Interim Director of the Translational and Molecular Imaging Institute, Director and Founder of the Imaging Science Laboratories and Cardiovascular Imaging Research, who is the technological wizard behind black-blood MRI. "It doesn't tell you anything about the vessel wall," says Dr. Fayad. It is here that plaques tend to accumulate.
What's more, current diagnostic tests reveal nothing about the nature of the plaques. "What matters is not just the size of the blockage, but its composition," says Dr. Fuster. "Not all plaques are created equal; some are more dangerous than others." Most troublesome are fatty plaques that are covered by a thin layer of fibrous tissue and are located within the vessel wall. When these plaques soften and rupture, as they often do, pieces of the plaque can break off, allowing a clot to clog an artery, triggering a heart attack.
Such plaques are not revealed by angiography, but they are by black-blood MRI. Using a variety of advances of his own design (e.g. software algorithms for capturing images in the split second when the heart is not in motion, special antennas for receiving MRI signals, and sophisticated image analysis software), Dr. Fayad has devised a way to create highly detailed picture of the vessel walls. "Ordinarily, blood flow creates a bright signal on MRI that obscures the image of the artery wall," the researcher explains. "We had to manipulate the images to black out the blood flow and leave the other structures clear. This method allowed us to look directly at the coronary artery walls." When viewed in cross section, the blood appears black, the walls stand out as white circles, and abnormalities such as plaque are plain to see.
Because MRI can also reveal the chemical composition of tissues, the test can be used to classify plaques, much as biopsies are used to characterize cancers. Thus, patients can be stratified according to their risk of heart attack.
Probably the most exciting aspect of black-blood MRI is that it sets the stage for individualized/personalized medicine. "Imaging is going to help determine which patients need specific therapies," according to Dr. Fayad. Imaging technology will also determine which patients need angioplasty or surgery right away, and which patients can wait."
Black Blood MRI has applications beyond the coronary arteries. Mount Sinai cardiologists are already using the technology to assess the carotid arteries that supply blood to the brain, frequent sites for clots that lead to strokes. Ultimately, this form of imaging could be used to evaluate vessels throughout the body. Indeed, the Mount Sinai team is also using them on other vessels within the body such as the aorta and arteries in the legs. Dr. Fayad expects this technology to become a standard diagnostic tool within a few years.
In the meantime, Dr. Fayad is attempting to wrest better images of blood vessels out of computed tomography, or CT, and positron emission tomography, or PET, scanning. Although CT scans provide less contrast than MRI, they are faster and less complicated to obtain. Similarly, although PET, provides less spatial resolution than MRI, the PET images provides metabolic information such as inflammation. Dr. Fayad believes that a multimodal approach using MRI, CT, and or PET may prove the ultimate diagnostic tool. "We could screen patients with CT first," he says. "If we find trouble, then we could zoom in with PET and MRI." Indeed, this year in 2009, Mount Sinai will be installing the first combined MRI/PET system along with one of the fastest CT scanner (256 multidetectors) in order to improve the characterization of atherosclerotic plaques using noninvasive multimodality imaging.
Other related cardiovascular imaging research activities ongoing in the Translational and Molecular Imaging Institute are:
- Imaging Acquisition and Analysis Methods: Development of novel multimodality cardiovascular imaging and analysis techniques using macro- and micro- Cardiovascular Magnetic Resonance (CMR), computed tomography (CT), positron emission tomography (PET), and optical imaging.
- Early Detection and Outcomes Prediction: Use of in vivo noninvasive multimodality imaging methods for the early detection of atherosclerosis in humans and for cardiovascular events and outcomes prediction.
- Clinical Trials and Drug Development: Use in vivo noninvasive multimodality imaging methods in clinical trials for the development and testing of novel therapeutics to treat atherosclerosis..
- Molecular Imaging: Development and use of novel multimodality imaging nanoparticulate systems to monitor fundamental cellular/molecular events in living subjects including patients.
- Drug Delivery: Development and use of novel targeted drug delivery nanoparticulate systems to improve the treatment of atherosclerosis in living subjects including patients.
For more details on cardiovascular imaging and the Translational and Molecular Imaging Institute program please see Dr. Fayad's profile.