Health-conscious Americans reach for margarine instead of butter and sneakers instead of cigarettes as a matter of route. Ask why and they may even be able to quote a few statistics like, stroke is the third leading cause of death in the United States. Ask what causes a stroke or how it is diagnosed and you may get a blank stare.

MRI showing a cross-section of the branches carotid artery. The external carotid artery (ECA), circulates blood to the face and is relatively normal. The internal carotid artery (ICA) circulates blood to the brain and shows the presence of a plaque.

A significant number of strokes are caused by carotid artery atherosclerosis. Atherosclerosis, commonly referred to as "hardening of the arteries," is a disease where there is build up of plaque in the blood vessel wall. Advanced plaque typically consists of lipid, such as cholesterol, a necrotic core and calcification, surrounded by cells and a matrix of connective tissue. Over the course of many years, build up of plaque material can lead to narrowing of the carotid artery lumen, or flow channel. Many studies have shown that the risk for stroke increases as the degree of luminal narrowing increases in the carotid artery. Duplex ultrasound is commonly used as a diagnostic test to quantify the degree of luminal narrowing.

"Patients may be referred for ultrasound screening when a physician hears a bruit in the neck during a routine physical examination," explains Thomas Hatsukami, associate professor of surgery at the UW School of Medicine and assistant chief of vascular surgery in the VA Puget Sound Health Care System. "Bruits are a rushing sound caused by vibration of the artery wall. Patients with multiple risk factors for atherosclerosis who are undergoing coronary artery bypass surgery or surgery for occlusive disease in the legs may also have a screening carotid ultrasound." Risk factors for atherosclerosis include smoking, high serum cholesterol levels, high blood pressure, diabetes or family history. The other primary indication for carotid duplex ultrasonography is a recent history of stroke or transient ischemic attack (TIA), where there are temporary symptoms that resolve within 12 hours. Symptoms include weakness, numbness, or tingling on one side of the body, difficulty with speech or loss of vision in one eye.

Other diagnostic tests for carotid disease include conventional angiography, CT angiography and magnetic resonance angiography. These tests have been shown to accurately measure the degree of narrowing in the carotid artery lumen. Hatsukami and his colleagues are interested in taking this one step further by examining the plaque itself. Their goal is to identify the features of carotid plaques, other than lumen narrowing, that pose a higher risk for stroke. Many investigators believe that the high-risk plaque is one that is more likely to undergo plaque rupture, which can lead to occlusion of the artery or release of material downstream to the brain and cause a stroke or TIA.

As an UW research fellow, Hatsukami began collaborating with magnetic resonance physicist Chun Yuan, professor of radiology. Since 1992 Hatsukami and Yuan have been conducting research validating high-resolution magnetic resonance imaging (MRI) as a tool to identify the high-risk atherosclerotic plaque. One of the major advantages of MRI is that it is capable of discriminating different tissue types, based on their molecular composition. Furthermore, it is a non-invasive test, making it ideal for serial studies of the carotid artery. Potential applications include serial examination of carotid atherosclerosis in prospective studies to learn how high-risk plaques develop, and in clinical research trials to directly assess the carotid plaque response to drug therapy, such as aggressive cholesterol lowering.

"We want to help clinicians decide which plaques are more dangerous than others," says Hatsukami. "This will permit us to better select those individuals who would benefit most from surgery, and those who would be best treated with medical therapy".

With funding through the National Institutes of Health, Hatsukami, Yuan and their colleagues have two ongoing studies using high-resolution MRI. In the first study, they are validating the MRI technique by performing carotid MRI in patients who have been scheduled for carotid endarterectomy. This is a procedure performed in selected individuals where the plaque is removed surgically. After surgery, the plaque is examined under the microscope and compared to the MRI findings. In the second study, they are recruiting volunteers with moderate narrowing in the carotid arteries and performing carotid MRI examinations every 18 months to learn how these plaques develop, and which particular plaque features pose the highest risk for subsequent stroke.

"We have found that this MRI technique is capable of identifying the lipid core, calcification, and fibrous cap characteristics with good sensitivity and specificity. Furthermore, we have found that there is a strong association between fibrous cap characteristics, as identified by MRI, and a recent history of TIA or stroke."

The fibrous cap is a layer of cells and matrix, such as collagen, that separate the blood flowing in the lumen from the necrotic core of the plaque. Based on studies of artery specimens removed at the time of surgery, it is felt that the plaques with thinned or ruptured fibrous caps pose a higher risk for stroke, and in the coronary arteries, myocardial infarction.

"For the first time, it appears that we have a non-invasive technique that is capable of identifying fibrous cap characteristics, without having to introduce catheters in the vessel, or having to remove the plaque surgically. Through our prospective MRI study, we hope to establish the risk that these plaque features pose for subsequent TIA or stroke."

Hatsukami presents "High Resolution Magnetic Resonance Imaging of Human Atherosclerosis In Vivo" at noon on Thursday, Sept. 27 in Turner Auditorium, D-209, Health Sciences Center. The lecture is the first in this year's Science in Medicine series and is open to everyone.

Hatsukami received his M.D. at the University of California, Los Angeles, in 1982. He came to the UW in 1982 as a surgical intern. From 1983 to 1992 he was a surgical resident, vascular fellow and senior research fellow. He became an acting assistant professor of surgery in 1992 and was an assistant professor from 1993 to 1999. Since 1992 Hatsukami as served as assistant chief of vascular surgery and an attending surgeon at the VA Puget Sound. He is a fellow of the America College of Surgeons and the American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology.