Plaque components hold key to diagnosis

January 7, 2005

Many researchers are convinced that the key to predicting and preventing unexpected heart attacks is the ability to image specific plaque components, such as the lipid core and the thickness of the fibrous cap. CT and MR, while making impressive strides in cardiovascular assessment, cannot reliably determine plaque composition or measure the fibrous cap in a meaningful way. A number of promising diagnostic tools could alert clinicians to the early development of atherosclerosis or help screen individuals with subclinical vulnerable plaque.

Many researchers are convinced that the key to predicting and preventing unexpected heart attacks is the ability to image specific plaque components, such as the lipid core and the thickness of the fibrous cap. CT and MR, while making impressive strides in cardiovascular assessment, cannot reliably determine plaque composition or measure the fibrous cap in a meaningful way. A number of promising diagnostic tools could alert clinicians to the early development of atherosclerosis or help screen individuals with subclinical vulnerable plaque.

Nearly 70% of unexpected heart attacks involve the rupture of vulnerable plaques. These lesions contain a lipid-rich core that expands to the point of degrading the fibrous cap that normally keeps the lipids at bay. The fibrous cap becomes thinner and thinner until a rupture ensues. People with fibrous caps thinner than 100 microns-and especially thinner than 50 microns-will almost certainly have a cardiac event within weeks or months, according to Dr. Marco Costa, a cardiologist

at the University of Florida, Jacksonville. But current noninvasive technology does not approach 100-micron resolution, and researchers are looking at other means to image subclinical cardiovascular disease.

Optical coherence tomography is the most promising invasive modality for imaging a weakening cap, Costa said. Its resolution of less than

20 microns is high enough to define the thickness of the fibrous cap. A group at Massachusetts General Hospital has used OCT to detect lipid pools, thin caps, and macrophages, which are associated with inflammation and plaque buildup.

A problem with OCT is that red blood cells cause interference between the catheter and the vessel wall, essentially preventing accurate assessment of the wall. If this problem can be overcome, OCT could become the intravascular ultrasound of the future.

Virtual histology, which is based on IVUS technology, is one method that Costa and colleagues have begun to use in their lab. They take the raw echo signal and develop a color-coded scheme based on amplitude and frequency levels. Areas that appear red are considered lipid core.

Another promising method involves thermography. In animal studies, a correlation has been documented between plaque development and a rise in temperature, and several companies are working on "thermo-wire" technology.

Elastography, the response of tissue to mechanical excitation or compression, may be another method to detect vulnerable plaque. Applying a force to plaque, which comprises both hard and soft materials, could feasibly determine its composition. Using IVUS, researchers have found more soft plaques in areas of high strain or compressibility, which have a higher incidence of macrophages as well. Areas with low shear stress also have been shown to have higher rates of inflammation. Costa postulated that a noninvasive tool capable of detecting areas of low shear stress could help stratify patients more likely to develop vulnerable plaques.

Cardiac MR holds great promise, particularly in the area of contrast agents designed to target specific molecules within plaques, Costa said. When the mechanism for clearing out lipids from the arterial wall fails, macrophages are engaged. When too many lipids begin to accumulate, the macrophages become overwhelmed and fill up with errant lipids. These lipid-filled macrophages, called foam cells, are a precursor of atherosclerosis.

Dr. Lee M. Mitsumori and colleagues at the University of Washington, Seattle successfully tested a paramagnetically labeled lipoprotein that could serve as a functional probe for the assessment of lipid metabolism in the vessel wall. Such an agent could identify the accumulation of toxic lipids well before anatomic evidence of a lesion is visible.