Correlation of Inflammation Assessed by ¹⁸F-FDG PET, Active Mineral Deposition Assessed by ¹⁸F-Fluoride PET, and Vascular Calcification in Atherosclerotic Plaque: A Dual-Tracer PET/CT Study

Abstract

Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by 18 F-FDG PET and ongoing mineral deposition as measured by 18 F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Methods: Forty-five patients were examined by whole-body 18 F-FDG PET, 18 F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient r s were used for statistical analysis of image-based results and cardiovascular risk factors. Intra-and interrater reproducibility were evaluated using the Cohen k. Results: 18 F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 6 0.7. 18 F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 6 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked 18 F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with 18 F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both 18 F-sodium fluoride and 18 F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. Conclusion: PET/ CT with 18 F-FDG and 18 F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

“…Other retrospective studies of similar patient populations have described association between the incidence of 18 F-NaF uptake in the peripheral vasculature and the number of cardiovascular disease risk factors and variations of Framingham cardiovascular risk scores (88,94,97). In one particular study 18 F-FDG and 18 F-NaF PET were compared retrospectively in a group of 45 patients who had undergone both types of assessment for oncological work up (89). 18 F-NaF showed a markedly increased propensity for colocalization with vascular calcification than did 18 F-FDG (77.1% vs. 14.5%), with co-localization of both radiotracers at the same site present in only 6.5% of cases.…”

18F-NaF Uptake by Atherosclerotic Plaque on PET/CT Imaging: Inverse Correlation Between Calcification Density and Mineral Metabolic Activity

“…To be included in the study, the patient had to have at least one calcification in the infrarenal abdominal aorta. Calcification was defined as a mural area having a minimum density of 130 HU (14). Patients were excluded from the study if they had a history of vasculitis, autoimmune disease, or systemic inflammatory disease or had received chemotherapy or radiotherapy in the preceding 8 wk, as previously proposed (18).…”

“…However, a calcification score represents only a static picture, not the pathophysiologic behavior of plaque, and may not fully correlate with a patient's clinical status and cardiovascular risk (6)(7)(8). Therefore, in view of the similarities between calcification formation and osteogenesis, functional studies with 18 FNaF PET have been performed to complement the calcification score with functional data on plaque mineral metabolism (9)(10)(11)(12)(13)(14)(15). These studies, however, highlighted a striking discrepancy between PET and CT in imaging plaque.…”

Imaging Cardiovascular Calcification

“…Several other studies have reported similar findings and have led to growing support for the use of 18 F‐NaF for imaging the process of microcalcification and visualizing ongoing mineral deposition within the atherosclerotic plaque 64, 99, 100, 101, 102, 103…”

“…Recently, substantial attention has been given to using 18 F‐NaF to investigate vascular calcification in the coronary arteries,22, 64 the aorta,99 and the carotid arteries,100 and it has rapidly gained acceptance as a useful tool for the investigation of plaque pathobiology.…”