Molecular Coronary Plaque Imaging Using 18F-Fluoride

Abstract

Background: Coronary ¹⁸F-fluoride positron emission tomography identifies ruptured and high-risk atherosclerotic plaque. The optimal method to identify, to quantify, and to categorize increased coronary ¹⁸F-fluoride uptake and determine its reproducibility has yet to be established. This study aimed to optimize the identification, quantification, categorization, and scan-rescan reproducibility of increased ¹⁸F-fluoride activity in coronary atherosclerotic plaque.

Methods: In a prospective observational study, patients with multi-vessel coronary artery disease underwent serial ¹⁸F-fluoride positron emission tomography. Coronary ¹⁸F-fluoride activity was visually assessed, quantified, and categorized with reference to maximal tissue to background ratios. Levels of agreement for both visual and quantitative methods were determined between scans and observers.

Results: Thirty patients (90% male, 20 patients with stable coronary artery disease, and 10 with recent type 1 myocardial infarction) underwent paired serial positron emission tomography-coronary computed tomography angiography imaging within an interval of 12±5 days. A mean of 3.7±1.8 ¹⁸F-fluoride positive plaques per patient was identified after recent acute coronary syndrome, compared with 2.4±2.3 positive plaques per patient in stable coronary artery disease. The bias in agreement in maximum tissue to background ratio measurements in visually positive plaques was low between observers (mean difference, -0.01; 95% limits of agreement, -0.32 to 0.30) or between scans (mean difference, 0.06; 95% limits of agreement, -0.49 to 0.61). Good agreement in the categorization of focal ¹⁸F-fluoride uptake was achieved using visual assessment alone (κ=0.66) and further improved at higher maximum tissue to background ratio values.

Conclusions: Coronary ¹⁸F-fluoride activity is a precise and reproducible metric in the coronary vasculature. The analytical performance of ¹⁸F-fluoride is sufficient to assess the prognostic utility of this radiotracer as a noninvasive imaging biomarker of plaque vulnerability.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110303 and NCT02278211.

Keywords: angiography; computed tomography angiography; coronary artery disease; fluorides; myocardial infarction.

Figure 1.

Background blood pool and cardiac ¹⁸F-fluoride activity. The mean standardized uptake value (SUV_MEAN; g/mL) in each region was compared by 3 observers across 2 scans. A, Box-plot of the median and the interquartile range of coefficients of variation for each region (black line, mean). There was no difference in the coefficients of variation of ¹⁸F-fluoride SUV_MEAN within intracardiac chambers (red), but there were increased coefficients of variation using systemic venous blood pool measurement (P<0.001) and interventricular septal myocardium (P<0.001) compared with measurement of SUV_MEAN ¹⁸F-fluoride activity in the left atrium. B, Box-plot of the median and the interquartile range of mean standardized uptake values for brachiocephalic, superior vena cava, right atrium, and interventricular septum (black line, mean). Note the low myocardial and background coronary arterial ¹⁸F-fluoride uptake compared with blood pool in the right atrium. BCV indicates brachiocephalic vein; IVS, interventricular septum; LA, left atrium; LV, left ventricle; NS, not-significant; RA, right atrium; RV, right ventricle; and SVC, superior vena cava. *P≤0.05; †P≤0.01; ‡P≤0.001; and §P≤0.0001.

Figure 2.

Culprit plaque ¹⁸F-fluoride activity on positron emission tomography-coronary computed tomography angiography (PET-CT). After acute myocardial infarction, culprit plaque ¹⁸F-fluoride activity can be measured in the right coronary artery (A–F), left anterior descending artery (G–I), and atrioventricular circumflex artery (J–L).

Figure 3.

Quantification of coronary ¹⁸F-fluoride activity. Visual identification of coronary ¹⁸F-fluoride activity was present in all ruptured plaques and 13.8% of stable coronary segments. The signal intensity of ¹⁸F-fluoride activity in coronary plaque was assessed both visually and semi-quantitatively by referencing to atrial blood pool activity (maximum target-to-background ratio [TBR_MAX]). Activity in coronary plaques was categorized into activity above blood pool (TBR_MAX >1.1), at or around blood pool (TBR_MAX 0.9–1.1), or below blood pool (TBR_MAX <0.9). Higher intensity signals were observed in stable segments compared with ruptured plaques.

Figure 4.

Bland-Altman plots of coronary ¹⁸F-fluoride activity. Correlation and Bland-Altman plots for scan-rescan reproducibility for coronary plaques at different levels of coronary ¹⁸F-fluoride activity (TBR_MAX; A and C, respectively). Correlation and Bland-Altman plots for interobserver reproducibility between 2 observers at different levels of ¹⁸F-fluoride activity (TBR_MAX; B and D, respectively). The shaded circles represent individual observations whilst the red and grey hatched lines represent the mean difference and 95% mixed-effects limits of agreement, respectively.