Atherosclerosis Burdens in Diabetes Mellitus: Assessment by PET Imaging

Abstract

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers ¹⁸F-fluorodeoxyglucose (FDG) or ¹⁸F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.

Keywords: 18F-fluorodeoxyglucose (FDG); 18F-sodium fluoride (NaF); PET; atherosclerosis; calcification; inflammation; quantification.

Figure 1

Modified PRISMA diagram showing literature selection.

Figure 2

Treatment effects on FDG uptake in atherosclerotic plaques. Representative FDG PET/CT with contrast media images (left) at baseline and (right) after four months of treatment with (bottom) pioglitazone or (top) glimepiride. Note the reduction in FDG uptake in the atherosclerotic plaque with pioglitazone treatment (arrows). Reprinted with permission from Ref. [41]. © 2022, The American College of Cardiology Foundation.

Figure 3

The recent ‘microcalcification-based’ perception of atherosclerosis development. Instead of showing inflammation, as FDG PET/CT is supposed to do, within the circles, this fabricated figure illustrates (upper panel) that a small, but NaF-avid (not shown directly) CT-detectable lesion in the proximal part of the right coronary artery has grown in size at follow-up after some years, at which point it has become more dense and less NaF avid due to a decrease in surface area. In contrast, (lower panel) a NaF-negative CT-visible lesion will usually not develop further. It remains unclear what the precise context for this phenomenon is; for details, see [52,53,54].

Figure 4

Limited co-localization of aortic wall FDG uptake and CT-detectable macrocalcification. PET images (a,d), CT images (b,e), and fused PET/CT images (c,f) of the aortic arch (upper panel) and abdominal aorta (lower panel) of a 72-year-old man with insulin-dependent diabetes. Macrocalcifications are visible in the low-dose CT images (white arrows in (b,e)), while faint and more pronounced NaF uptake in other locations is detectable by PET (black arrows in (a,d)). The SUVmax and SUVmean were 2.9 and 2.2 for the aortic arch, and 2.6 and 2.4 for the abdominal aorta, respectively. Reprinted with permission from Ref. [34]. © 2022, Hellenic Society of Nuclear Medicine.

Figure 5

Schematic presentation of the arterial uptake of FDG and NaF in healthy individuals (A) and diabetic patients (B) as a function of age, as well as the effect of therapy (pioglitazone) on FDG uptake and the unknown effects (dotted lines) of any future attempts to influence NaF uptake.