The past 15 years have witnessed a remarkable expansion in noninvasive cardiovascular imaging technology. Indeed, we now have access to a wide spectrum of modalities, each offering distinct and potentially complementary information with respect to the pathophysiology of atherosclerosis. Considerable interest has surrounded the use of this technology to improve cardiovascular risk prediction so that we can better identify high-risk patients, allowing us to intervene and avert subsequent myocardial infarction. For many years, the major focus in atherosclerosis imaging research has been to identify individual coronary plaques at high risk of rupture, the so-called vulnerable plaque. Ultimately, this strategy has failed to have a major impact on clinical care, prompting many to consider a switch of emphasis to pan-coronary and pan-vascular assessments of disease activity that may be more closely related to the vulnerable patient: those subjects at highest risk of cardiovascular events. This talk will describe molecular imaging strategies to tackle this issue; in particular, how the measures of disease activity targeted to both inflammation and other processes might be used to identify patients at highest risk of stroke and myocardial infarction. This provides just one example of the potential of molecular imaging in the clinical and translational setting and the concept covered here can be applies to a variety of disease processes such as cancer and neurodegeneration. A limitation of anatomic plaque assessments is that although they provide an indication as to how much plaque has accumulated over time, they give no indication as to the current activity of the disease process. They are, therefore, unable to distinguish those patients who have burnt-out, stable disease that is no longer metabolically active versus those with active atheroma. This is of potential importance because patients with active disease will develop multiple unstable plaques over time; and although the majority will heal without incident, overall there will be an increased probability that one will rupture when the blood is thrombogenic and cause an event. The poor prognosis associated with an active disease process was suggested by studies investigating disease progression. The emergence of molecular imaging now allows us to do exactly that. Molecular tracers targeted to pathological processes of interest are injected into the body, where they accumulate at sites of increased disease activity. These tracers are labeled with an imaging re- porter that provides signal on the relevant imaging platform. Potentially, the activity of any disease process can be assessed depending on the availability of a suitable imaging tracer and scanner. However, in practice, the strict requirements of the US Food and Drug Administration (FDA) for regulatory approval make the development of novel clinical tracers both time consuming and expensive. Human research has, therefore, largely focused on tracers already approved for noncardiac conditions but which target disease processes relevant to atherosclerosis and acute plaque rupture. In particular, markers of inflammation activity have been evaluated. These are discussed in detail here, although an array of other tracers targeting processes such as angiogenesis, hypoxia, and plaque hemorrhage are also in development and will be discussed.

Acknowledgements

No acknowledgement found.

References

Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis. (2016). Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis., 119(2), 330–340. http://doi.org/10.1161/CIRCRESAHA.116.307971