PET and SPECT studies allow for the analysis of atherosclerotic plaque composition by imaging the inflammatory process, apoptosis, and metabolism of lipids.

The risk of plaque rupture and thrombus formation depends not only on the thickness of the fibrous cap surrounding the plaque, but also on the composition/state, e.g., the presence of lipid and the inflammation initiated by macrophages [8–11]. The inflammatory process is linked to plaque instability and the risk of acute vascular events. Among the effects, inflammation leads to enzymatic damage and subsequent rupture of the fibrous cap.

Due to the active inflammation, macrophages are of interest in monitoring atherosclerosis. They have a significant glycolytic activity, which can be imaged in PET after the administration of 18FDG [22]. 18FDG is a glucose analog, which is carried by the same transport mechanisms, and is subsequently transformed in the Krebs cycle, taking part in the first step, phosphorylation, only. As a result, the uptake of 18FDG is directly proportional to the glucose transport mechanisms and the activity of hexokinase and therefore the metabolic activity of the tissue.

18F-FDG-PET studies were introduced into clinical practice over 20 years ago and are most commonly used to evaluate neoplastic and inflammatory diseases. Tawakol et al. showed that the degree of 18FDG uptake strictly correlates with the presence of macrophages in the plaque (Fig. 1) [22]. The technique potentially allows for diagnosis of inflammatory vascular lesions, as well as treatment monitoring.

PET has greatly improved after the introduction of hybrid PET/CT [23]. The CT imaging allows for an analysis of density of the surrounding tissue, which is then used to correct the attenuation phenomenon. The second advantage of this technique is image fusion from the two modalities, allowing good anatomical correlation, some assessment of plaque structure, as well as information on the metabolic activity. PET also allows for the evaluation of structures in multiple vascular territories at once, which is advantageous in this systemic disease. Studies have shown that inflammatory changes in atherosclerotic plaques are located diffusely throughout the vascular system. If a plaque is demonstrated to have inflammatory changes, it is common for the morphological changes to be present in other plaques to a similar degree. The presence of a plaque in one carotid artery is often connected with a contralateral, but is more commonly associated with plaques located within the same anatomical area. It has been shown that the uptake of 18FDG in atherosclerotic plaques does not correlate with the degree of calcification. This suggests that calcification is the final step in the disease process and is a more stable state. This observation shows the potential role of functional studies in disease work-up. The systemic nature of the disease can also be determined as illustrated with the increased 18FDG uptake in the area of atherosclerotic carotid plaques of patients who have had a previous myocardial infarction and a higher concentration of serum inflammatory markers (including matrix metalloproteinase (MMP 3 and MMP 9) and C-reactive protein (CRP)).

PET/CT allows for the evaluation of the effectiveness of new generation drugs, which reduce plaque inflammation in some way, by examining their effect on plaque stabilization. Tahara et al. [24] studied the effect of simvastatin on the degree of 18FDG uptake in atherosclerotic plaques in two patient groups: those treated with simvastatin vs. low-cholesterol diet alone (overall population 43 patients). Measuring the 18FDG uptake values before treatment and at 3 months, the18F-FDG uptake in atherosclerotic plaque was markedly smaller in patients treated with simvastatin compared to diet alone, with an added correlation of decreased 18FDG uptake with higher high-density lipoprotein (HDL) levels. Lee et al. [25] established that PET allows for objective conclusions of the effect of lifestyle on disease progression. Prior to the observational period, 362 anatomical areas with increased 18FDG uptake were identified in a cohort of 60 patients. After 17 months the number of areas of increased uptake reduced to 124. The authors also evaluated the whole body 18FDG index. After lifestyle changes, the index decreased from 1.39 to 0.53, which correlated with a decreased total and low-density lipoprotein (LDL) cholesterol concentration. This data illustrates that PET is a useful tool in the study of disease progression, as well as the effectiveness of drugs and lifestyle modification in progression. Fayad et al. [26] used 18FDG-PET/CT combined with MR to study the effect of dalcetrapib on plaque morphology. Dalcetrapib modulates cholesteryl ester transfer protein (CETP) activity to raise HDL cholesterol. The authors were able to demonstrate that PET as well as MRI are acceptable techniques to evaluate drug effectiveness. Furthermore, they have shown that dalcetrapib acts positively on the structure and functional parameters of vessel wall plaques.

MRI is as an established imaging modality for plaque morphology and stenosis evaluation. The technique does not require ionizing radiation, provides high-resolution images, and using multiple sequences can evaluate disease characteristics. The use of different sequences allows for evaluation of plaque structure [28], without the need of intravenous contrast, although this further enhances the technique [29, 30]. It is possible to assess the fibrous cap, lipid-rich necrotic core, or possible intraplaque hemorrhage. In contrast, calcification may be more difficult to analyze.