Quantifying microcalcification activity in the thoracic aorta

Alexander J Fletcher, Maria Lembo, Jacek Kwiecinski, Maaz B J Syed, Jennifer Nash, Evangelos Tzolos, Rong Bing, Sebastien Cadet, Gillian MacNaught, Edwin J R van Beek, Alistair J Moss, Mhairi K Doris, Niki L Walker, Damini Dey, Philip D Adamson, David E Newby, Piotr J Slomka, Marc R Dweck, Alexander J Fletcher, Maria Lembo, Jacek Kwiecinski, Maaz B J Syed, Jennifer Nash, Evangelos Tzolos, Rong Bing, Sebastien Cadet, Gillian MacNaught, Edwin J R van Beek, Alistair J Moss, Mhairi K Doris, Niki L Walker, Damini Dey, Philip D Adamson, David E Newby, Piotr J Slomka, Marc R Dweck

Abstract

Background: Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta.

Methods: Twenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores.

Results: Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease.

Conclusions: AMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.

Keywords: Image analysis; Modalities; Molecular imaging agents; Others; PET; Technical; Tests; Tracers.

Conflict of interest statement

The authors have no relevant conflicts of interest to declare.

© 2021. The Author(s).

Figures

Figure 1
Figure 1
18F-Sodium fluoride positron emission tomography and computed tomography in a patient with marked aortic wall uptake. An illustrated representation of standard whole vessel (A) and most diseased segment (B) as well as novel aortic microcalcification (C) methods for quantifying uptake. Average time taken to complete each method is shown. AMA, aortic microcalcification activity; Asc, ascending aorta; CT, computed tomography; PA, pulmonary artery; PET, positron emission tomography; LV, left ventricle; RA, right atrium; TBR, tissue to background ratio
Figure 2
Figure 2
Step-by-step outline of measuring aortic microcalcification activity. (A) Co-register register 18F-sodium fluoride overlay to computed tomography image in three orthogonal planes using landmarks of the sternum, spine, and aortic wall (blue arrows). (B + C) Place a 2 cm3 region of interest in the centre of the right (B) and left (C) atrium. The background activity is the cumulative SUV per cm3 from the volumes of interest in the left and right atrium. (D, F) With the 18F-sodium fluoride overlay turned off, a centreline function is used to draw the ascending aortic volume of interest in multiplanar reconstruction images. Perpendicular to the aorta, the volume of interest starts at the sinotubular junction (D) and finishes at the slice just proximal to the origin of the brachiocephalic artery (E). The width of the volume of interest is increased to the maximum ascending aortic diameter + 4 mm (F + H). The 18F-sodium fluoride overlay is reinstated to ensure good coverage (I). The ascending aortic AMA, and volume are calculated (I). The aortic arch volume of interest is drawn with the same method as the ascending aorta, starting with the slice immediately distal to the ascending aortic volume of interest (J), and finishing with the slice after the origin of the left subclavian artery (K). The width of the aortic arch volume of interest is increased to the maximal arch dimeter + 4 mm (M + N). The 18F-sodium fluoride overlay is reinstated to check good coverage and calculate the aortic arch AMA and volume (N). (O) Provides the formula for calculating overall AMA, whilst (P) uses the values in the current case to provide a working example of AMA calculation
Figure 3
Figure 3
Hybrid 18F-sodium fluoride positron emission tomography and computed tomography coronal images of the ascending aorta and arch in four patients with varying patterns and intensity of aortic wall 18F-sodium fluoride activity: (A) Homogenously low activity across the ascending aorta and arch; (B) Generally low activity with a single high intensity lesion (blue arrow); (C) Moderate activity with a high intensity lesion (blue arrow); (D) High and intense activity throughout ascending aorta and arch. Note that (B) and (C) have similar values for most diseased segment maximum tissue to background ratio (highlighted in yellow) despite substantially different overall activity (aortic microcalcification activity values highlighted in green). AscAo, ascending aorta; AMA, aortic microcalcification activity; AoArch, aortic arch; AoRoot, aortic root; MDS, most diseased segment; LV, left ventricle; RA, right atrium; RPA, pulmonary artery; SUV, standardised uptake measurement; TBR, tissue to background ratio
Figure 4
Figure 4
Scan-rescan reproducibility. Bland-Altmann plots with mean error (blue line) and 95% limits of agreement (red lines) for whole vessel standardized uptake value mean (A), standardized uptake value max (B), tissue to background ratio mean (C), tissue to background ratio max (D), most diseased segment tissue to background ratio mean (E) and tissue to background ratio maximum (F) and aortic microcalcificaion activity (G) methods. Y-axis limits are set to the method mean value of the method concerned. AMA, aortic microcalcification activity; CR, coefficient of reproducibility; ICC, intraclass correlation coefficient, MDS, most diseased segment; LOA, limits of agreement; SD, standard deviation; TBR, tissue to background ratio
Figure 5
Figure 5
Scatterplots with Pearson’s correlation coefficients for the various methods of quantifying 18F-soidum fluoride uptake in the thoracic aorta compared with Framingham Risk Score for stroke in each patient. (A) Aortic macrocalcification activity (B) whole vessel TBRmean (C) whole vessel TBRmax (D) most diseased segment TBRmean (E) most diseased segment TBRmax. AMA, aortic microcalcification activity; TBR tissue to background ratio

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