Prof. Eike Nagel,
Dr. Narula from Orange, US, started the session by reviewing the morphology of vulnerable plaques and discussing why patients die of sudden cardiac death. The main reasons are that plaques grow outward, rather than inward (positive remodeling) and thus cause no luminal narrowing or symptoms. They then become unstable and rupture. CT is able to differentiate soft and more vulnerable plaques from luminal stenoses and stable older plaques. However, in a series of more than 1000 patients, only 45 patients showed signs of vulnerable plaques, 10 of them then developed an acute coronary. This demonstrates that this technique is mainly useful for differentiating subjects with a very high risk (i.e. > 10% likelihood of an event within one year) from subjects with a high risk (i.e. > 2% likelihood of an event within one year). The exact algorithms and the exact place of CT in the workup of a high risk population remain to be defined. Dr. Rudd from Cambridge, UK, then reported on the status of PET/CT imaging to detect vulnerable plaques. FDG PET reflects macrophage activity and inflammation and it can be used to monitor the effect of therapy. However, both applications are restricted to the aorta and the carotid arteries. This is due to the healthy heart taking up FDG, and thus creating too much background signal. In principle, this background noise can be suppressed by lipid loading for three days, which seems rather unpractical for a clinical application. Alternatively, novel tracers can be used, such as PK 11195, FEDAA or Ga-DOTATATE. At this stage, it is not known if the ability of PET to reflect inflammation can be used to predict clinical events. This is being evaluated in ongoing studies. Dr. Kaufmann from Basel, CH, led the discussion on microbubble imaging with echo techniques for the assessment of vulnerable plaques. In principle, this works in a similar manner to other echo techniques using contrast agents by exciting the microbubbles and measuring the resulting vibrations. The microbubbles can be connected to ligands which then bind to specific targets, such as selectins, VCAM-1 or tissue factor. Studies in mice have demonstrated that this technique makes it possible to detect endothelial dysfunction and vascular inflammation in advanced disease. First results in animals with early disease were also promising. The targeting approach may also be interesting for the development of new drugs, since drug delivery and disease monitoring could be performed with the same agent. Dr. Fayad from New York, US, finished the session off by leading the audience through novel hardware developments, such as PET/MRI. Combined PET/MR imaging combines the high contrast and anatomical information of MR with the very high sensitivity of PET for tracer detection. Unfortunately, the development of these systems is difficult due to the magnetic field of the MRI, which makes integration of standard PET equipment difficult. However, new developments are very promising and first whole body PET/MR systems are expected early next year. Dr. Fayad then reported on multicolor CT imaging (edge imaging) which allows for very low radiation CT in combination with improved differentiation of structures or even targeted contrast agents.
To summarize the session, at this stage there is no single technique available to detect vulnerable plaques in coronary arteries and to predict events. Ongoing research is promising, but the target remains difficult to solve and practical results are still some years ahead.
Imaging of atherosclerotic plaques: newer trends and developments
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