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

Several studies have highlighted the role of vascular F-18-NaF uptake as a marker of ongoing calcium deposition. However, accumulation of F-18-NaF is often inconsistent with localization of arterial plaque. Calcification activity and thus F-18-NaF uptake might prevail in the earlier plague stages. To test this hypothesis, we evaluated F-18-NaF uptake in plaque of 3 different densities, using density as a marker of calcification progression. We also tested whether attenuation-weighted image reconstruction affects F-18-NaF uptake in the different plaque stages. Methods: Sixty-four oncologic patients (14 men and 50 women; mean age, 65.3 +/- 8.2 y; range, 26-81 y) underwent F-18-NaF PET/CT. A volume of interest was drawn on each plaque within the infrarenal aorta to assess mean standardized uptake value and attenuation (in Hounsfield units [HU]). Plaque was then categorized as light (<210 HU), medium (211-510 HU), or heavy (>510 HU). Standardized uptake value was normalized for blood F-18-NaF activity to obtain the plaque target-to-background ratio (TBR). During this process, several focal, noncalcified areas of F-18-NaF were identified (hot spots). The TBR of the hot spots was computed after isocontour thresholding. The TBR of a noncalcified control region was also calculated. In 35 patients, the TBR of non-attenuation-corrected images was calculated. Results: The average TBR was highest in light plaque (2.21 +/- 0.88), significantly lower in medium plague (1.59 +/- 0.63, P < 0.001), and lower still in heavy plaque (1.14 +/- 0.37, P < 0.0001 with respect to both light and medium plaque). The TBR of the control region was not significantly different from that of heavy plaque but was significantly lower than that of light and medium plaque (P < 0.01). Hot spots had the highest absolute TBR (3.89 +/- 1.87, P < 0.0001 vs. light plaque). TBRs originating from non-attenuation-corrected images did not significantly differ from those originating from attenuation-corrected images. Conclusion: Our results support the concept that F-18-NaF is a feasible option in imaging molecular calcium deposition in the early stages of plaque formation, when active uptake mechanisms are the main determinants of calcium presence, but that retention of F-18-NaF progressively decreases with increasing calcium deposition in the arterial wall. Our data suggest that non-attenuation-corrected reconstruction does not significantly affect evaluation of plaque of any thickness.