Ex-vivo Characterization of Coronary Atherosclerotic Plaque

Coronary artery disease (CAD) remains a major cause of death in industrialized countries despite significant therapeutic advances. The early and accurate diagnosis of coronary artery disease remains a healthcare imperative. Previous studies have demonstrated that CAD invariably presents as an acute coronary syndrome or a sudden cardiac death. Both ex vivo and in vivo analysis have determined that these presentations correlate with specific plaque characteristics. When these "high risk " plaques rupture they form a clot that occludes the vessel contributing to ischemia, infarction and malignatn arrythmia. Angiographic and intravsacular ultrasound (IVUS) studies demonstrated that these culprit lesions occur in the proximal coronary arteries are non-occlusive and predominatly lipid rich. These characteristics appear to define a "high risk" coronary artherosclerotic plaque. Unfortunately both angiography and IVUS are limited by their invasive nature and associated morbidity . Cardiac computed tomography (CCT) emerged ten years ago as an alternative diagnostic technique for patients with suspected coronary artery disease. Numerous studies have been published demonstrating the high diagnostic accuracy of CCT for the detection of obstructive coronary artery stenosis, and moderate accuracy for the detection of non-obstructive plaque. Furthermore initial reports suggest that CCT may be able to define atherosclerotic plaque characteristics beyond stenosis quantification. The ability to accurately identify plaque and to determine the degree of stenosis is of great clinical importance as both factors help determine prognosis and treatment. A robust CCT technique is highly desirable as it is non-invasive, rapid, and likely to be cost effective. However CT platforms to date have all had significant limitations in both spatial and temporal resolution therefore limiting what could be reliably achieved in non-invasive CCT imaging. Dual source computed tomography (DSCT) became a clinical reality within the last year. This technique has a higher temporal resolution than any of the prior CT platforms. Initial studies suggest excellent test characteristics and therefore DSCT may be a reliable and highly accurate tool for providing clinically useful information. Validation of this new technique is therefore required and to date there has been only limited ex-vivo assessment. The aim of the study will be to prospectively validate DSCT for the detection, quantification, and characterization of coronary atherosclerotic plaque as compared to intravascular ultrasounds, optical coherence tomography and histology. Furthermore, we will determine the reproducibility of this technique (inter- and intraobserver variablity) and the impact of heart rate of DSCT-based assessment of coronary atherosclerotic plaque in an ex vivo setting. Two main experiments will be performed. The first will assess the limitation of DSCT in the characterisation of noncalcified plaque using a phantom based surrogate. Stenosis, plaque size, geometry and special plaque characteristics (lipid pools) will be assessed using three phantom designs. The second step will require ex vivo coronary arteries that will be assessed by DSCT and compared to IVUS, OCT histoptahology. Accuracy of plaque characterisation will be assessed using different heart rates. With this project we hope to prove the high impact of the new techology of the DSCT in coronary artery disease. We will try to assess a validated protocoll that can easily be used in clinical routine to determinate plaque composition and we will try to clearly characterize a non calcified plaque (lipid and fibrous) to further introduce it in clinical routine. Finally we hope to proove DSCT to be an accurate modality in measurung the size of a plaque, so that in further studies the benefit of medical treatment to reduce plaque size can be shown.