Adequate risk assessment for acute coronary events (myocardial infarction and sudden cardiac death) is important for efficiently allocating resources for preventative measures. Advances in multi- detector computed tomography (MDCT) technology have expanded its use from traditional radiologic imaging to cardiac applications that enabled non-invasive coronary angiography with high diagnostic accuracy for detecting obstructive coronary artery disease. In addition to mere anatomic characteristics of coronary artery disease, there is immense interest in exploring the metabolic activity of coronary atherosclerotic plaque as it may inform us which plaques are or are not prone to trigger acute coronary events. An established target for assessing atherosclerotic plaque metabolic activity is the presence and extent of neovascularization within plaques. Investigations using MRI demonstrated the feasibility of detecting neovascularization in human carotid artery plaques but no data for such assessment are available in the much smaller coronary artery plaques. MDCT has superior spatial resolution compared to MRI and thus appears better positioned for detailed coronary artery imaging. We hypothesized that highly metabolically active atherosclerotic plaques will be distinct from less active plaques due to enhanced contrast uptake in tissue with greater vascularization. To test this hypothesis, we propose to image coronary arteries in an animal model using MDCT with histopathologic comparison. Specifically, we will perform MDCT in 9 pigs with induced coronary atherosclerosis and neovascularization and analyze images using a novel, normalized analysis of tissue X-ray attenuation. In a second step, we will use micro CT for ex vivo imaging of coronary arteries. Micro CT has superior spatial resolution compared to conventional MDCT but it is not available for clinical use. Micro CT may confirm our hypothesis in case MDCT fails to detect an actual difference in tissue attenuation among coronary atherosclerotic plaques of greater or lesser vascularization. Finally, we will compare the presence and degree of vascularization as detected by MDCT and micro CT with the results of histopathology. The significance of this proposal lies in the possibility of identifying a novel method for detecting coronary atherosclerotic plaques that are more metabolically active and possibly vulnerable, i.e., associated with higher coronary event risk, using tools that are widely available. This proposal, therefore, may lead to a significant advancement in our ability to identify patients at increased risk from acute coronary events which may be immediately applicable to many patients.

Public Health Relevance

This research intends to develop a method for characterizing the biologic activity of plaque in heart arteries seen by computed tomography (CT). The methods proposed in this research may help identifying patients who are most likely to benefit from specific treatments for plaque build-up in their heart arteries and those who are not likely to benefit. Therefore, this research may help allocate resources more efficiently, reduce unnecessary treatment risks for patients, and decrease the financial burden on our health care system.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Exploratory/Developmental Grants (R21)
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Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
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Rao, Anupama
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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