Carotid Plaque Imaging to Predict Ischemic Stroke

Max Wintermark, M.D.

University of California, San Francisco, San Francisco, CA

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

June 2008, for 3 years

Funding Amount:


Lay Summary

Assessing Stroke Risk by Carotid Wall Imaging

This study will employ computer assisted tomography (CT) scanning of patients with carotid atherosclerotic disease to see if certain abnormal features of the carotid artery wall can be used to predict stroke risk in these patients.

Carotid atherosclerotic disease is a degenerative condition characterized by the build-up of fatty products and calcium (plaques) in the walls of the large arteries of the neck. It is a common condition, affecting 75 percent of men and 65 percent of women over age 64. The disease carries with it a high risk of stroke, because carotid plaques can break up and release material into the circulation of the brain that causes clots.

Currently, severity of carotid artery disease is assessed by the degree of narrowing (or “stenosis”) of the artery. Treatment of patients in which artery narrowing is greater than 70 percent is well established: stroke risk in these patients is significantly reduced by “endarterectomy,” (surgical removal of plaque from the artery). In most patients with carotid artery disease who have less than 70 percent artery narrowing, however, the degree of stenosis does not predict stroke risk, although a significant proportion of the patients do go on to have strokes. Because it is impossible to determine which individuals with less severe stenosis will have strokes, no guidelines currently exist for treating these patients.

To address this gap, the investigators will assess six other features of the diseased carotid artery (including, for example, wall thickness and the presence of carotid plaque ulcerations) by CT scan and determine if any of these features predict stroke risk. They will begin by examining the carotid artery on the side on which the stroke occurred in 200 patients, and determine which of these six features, if any, were present in carotid arteries of 200 patients who had received a carotid artery CT scan at UCSF between 2001 and 2007 for diseases other than stroke. They will then analyze 360 carotid stroke patients and compare the carotid artery on the side of the stroke to the carotid artery on the opposite side. Finally, they will study 320 patients who were free of carotid stroke when first scanned at UCSF, and compare the carotids of those who subsequently suffered a stroke and those who did not. From these comparisons, they plan to determine which combinations of the six factors may help to predict risk of carotid artery stroke.

Significance: Identifying a predictor of stroke risk in the population of patients with less severe coronary artery disease could help prevent a large number of strokes every year.


Carotid Plaque Imaging to Predict Ischemic Stroke

Carotid artery disease is common in the general population (75% in men and 65% in women >64). Clinical management of patients with a degree of carotid stenosis >70% is well established. However, in a large majority of cases (>90% of cases), carotid stenosis is <70%. While <70% carotid stenosis is associated with a low individual risk of ischemic stroke (1.3% to 3.3% annually), its high prevalence in the general population translates into a large number of ischemic strokes on a population level. In these patients with <70% carotid stenosis, the exact degree of luminal narrowing fails to predict the associated risk of stroke. Recently, a concept has emerged that direct assessment of the atherosclerotic process within the carotid wall would be a better predictor of the risk of stroke than characterizing its indirect impact on the adjacent lumen—an approach that is made possible by the ability of imaging techniques, such as ultrasound, MRI, and CT, to assess the carotid artery wall in addition to the lumen.

The goal of this research is to identify a carotid artery wall feature (or a combination thereof) that would allow differentiation in patients with <70% carotid stenosis between those at high risk and those at low risk of ischemic stroke. In pursuit of this goal, we propose to conduct a nested study in a retrospective cohort of patients from our institution who had a CT-angiogram of their carotid arteries between 2001 and 2007 (n=4,891). We will compare and evaluate 6 carotid artery wall features (maximal carotid wall thickness, carotid plaque ulcerations, thickness of the fibrous cap, lipid-rich necrotic core, intraplaque hemorrhage, calcifications). The primary outcome will be ischemic strokes of carotid origin. We propose three specific aims, which will test the three following hypotheses, with specific attention paid to patients with <70% carotid stenosis:

Aim 1: To test the hypothesis that a combination of one or several among 6 carotid artery wall features discriminates carotid stroke patients from non-carotid stroke patients.

Aim 2: To test the hypothesis that a combination of one or several among 6 carotid artery wall features discriminates the side ipsilateral to the stroke from the contralateral side in carotid stroke patients.

Aim 3: Among patients free of stroke at baseline, to test the hypothesis that a combination of one or several among 6 carotid artery wall features predicts incident carotid ischemic stroke during follow-up.

Investigator Biographies

Max Wintermark, M.D.

Dr. Max Wintermark is a graduate of medicine from Lausanne University in Switzerland. He received his professional training in radiology from Lausanne University Hospital, as well as from the University of California San Francisco. A pioneer in the development of Perfusion-CT with patented work pertaining to the technique, Dr. Wintermark is a published author of numerous articles and text chapters in the field of cerebrovascular imaging. Dr. Wintermark is currently an Assistant Professor in Residence in the Neuroradiology Section at the University of California, San Francisco.