PET Imaging of Atherosclerotic Disease: Advancing Plaque Assessment from Anatomy to Pathophysiology

Abstract

Atherosclerosis is a leading cause of morbidity and mortality. It is now widely recognized that the disease is more than simply a flow-limiting process and that the atheromatous plaque represents a nidus for inflammation with a consequent risk of plaque rupture and atherothrombosis, leading to myocardial infarction or stroke. However, widely used conventional clinical imaging techniques remain anatomically focused, assessing only the degree of arterial stenosis caused by plaques. Positron emission tomography (PET) has allowed the metabolic processes within the plaque to be detected and quantified directly. The increasing armory of radiotracers has facilitated the imaging of distinct metabolic aspects of atherogenesis and plaque destabilization, including macrophage-mediated inflammatory change, hypoxia, and microcalcification. This imaging modality has not only furthered our understanding of the disease process in vivo with new insights into mechanisms but has also been utilized as a non-invasive endpoint measure in the development of novel treatments for atherosclerotic disease. This review provides grounding in the principles of PET imaging of atherosclerosis, the radioligands in use and in development, its research and clinical applications, and future developments for the field.

PET/CT Imaging of Unstable Carotid Plaque with 68Ga-Labeled Somatostatin Receptor Ligand

“…Radionuclide imaging has the advantageous capability of directly probing molecular mechanisms in vivo using radioactive tracers (8).…”

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study

“…Measuring plaque FDG activity provides important information on intraplaque inflammation, which is a crucial mediator of plaque rupture and thromboembolism [19]. FDG, a radioactive tracer and a glucose analog, is taken up by cellular glucose transporters, which are upregulated during atherogenesis due to hypoxia within the core of the atherosclerotic plaques [15, 41]. The fate of an atherosclerotic plaque is by and large determined by the actions of macrophages, as macrophages are found in increased density in unstable coronary lesions [9–11].…”

“…These pro-inflammatory macrophages have an elevated glycolytic rate, avidly accumulate FDG and are implicated in atherosclerosis [9–14]. FDG-PET has been used in research studies looking at vascular inflammation to detect and quantify atherosclerosis and subsequent plaque destabilization [15]. Studies have shown that arterial FDG uptake correlates with symptomatic, unstable plaque, and macrophage burden [12, 16] and has proven to be a useful prognostic imaging tool to identify patients most at risk for early CVD recurrence [17–20].…”

Coronary Atherosclerosis Imaging

“…Hence, they cannot accurately distinguish between patients with stable disease from those with increased disease activity, expressed by macrophages and microcalcifications which are associated with increased risk of developing acute CV events. Nuclear imaging such as PET can visualize different components of the atherosclerotic process, thus providing a highly sensitive assessment of coronary disease activity [91]. Specific radioactively labelled tracers targeted to pathological components of the atherosclerotic process, such as macrophages ( 18 F-fluorodeoxyglucose and 68-Gallium-dotatate targeting the somatostatin receptor on the surface of macrophages) and microcalcification ( 18 F-sodium fluoride), accumulate at sites of increased disease activity, releasing radiation which are detected by the PET scanner [83].…”