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Association between atherosclerotic cardiovascular disease risk score estimated by pooled cohort equation and coronary plaque burden as assessed by NaF-PET/CT.

ABSTRACT: Pooled Cohort Equations (PCE) combines metabolic and non-metabolic parameters to predict the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Therefore, we hypothesize that ASCVD risk score is correlated to global cardiac microcalcification, as assessed by ¹⁸F-sodium fluoride-positron emission tomography/computed tomography (NaF-PET/CT). Sixty-one individuals (53.4±8.9 years, 32 females, 100% Caucasian) without known ASCVD underwent NaF-PET/CT imaging. Global cardiac average SUVmean (aSUVmean), also known as the Alavi-Carlsen Calcification Score, was calculated across manually defined regions of interest on each axial slice for each individual. The 10-year ASCVD risk score was determined for each individual using the PCE as per ACC/AHA guidelines, and then individuals were categorized into low-, borderline-, intermediate-, and high-risk groups based on their score. Linear regression analysis was applied to compare each individual's ASCVD score and aSUVmean. Global cardiac aSUVmean stratified by groups estimated by 10-year ASCVD risk score were 0.67±0.09 for low risk (n=32), 0.70±0.11 for borderline risk (n=10), 0.72±0.10 for intermediate risk (n=17), and 0.78±0.10 for high risk (n=2). ASCVD risk score was significantly correlated to aSUVmean (r=0.27, P=0.03). This is among the first studies to compare ASCVD risk scores to cardiac plaque burden as assessed by NaF-PET/CT. Large, prospective studies are needed to further investigate the potential of NaF uptake in ASCVD.

SUBMITTER: Borja AJ

PROVIDER: S-EPMC7724277 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association between atherosclerotic cardiovascular disease risk score estimated by pooled cohort equation and coronary plaque burden as assessed by NaF-PET/CT.

Borja Austin J AJ Bhattaru Abhijit A Rojulpote Chaitanya C Hancin Emily C EC Detchou Donald K DK Patil Shivaraj S Gonuguntla Karthik K Karambelkar Pranav P Chinta Sree S Vuthaluru Kiranmayi K Werner Thomas J TJ Gerke Oke O Høilund-Carlsen Poul F PF Alavi Abass A

American journal of nuclear medicine and molecular imaging 20201215 6

Pooled Cohort Equations (PCE) combines metabolic and non-metabolic parameters to predict the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Therefore, we hypothesize that ASCVD risk score is correlated to global cardiac microcalcification, as assessed by <sup>18</sup>F-sodium fluoride-positron emission tomography/computed tomography (NaF-PET/CT). Sixty-one individuals (53.4±8.9 years, 32 females, 100% Caucasian) without known ASCVD underwent NaF-PET/CT imaging. Global cardiac av ...[more]

PMID: 33329933

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Project description:Background18F-FDG-PET(/CT) is increasingly used in studies aiming at quantifying atherosclerotic plaque inflammation. Considerable methodological variability exists. The effect of data acquisition and image analysis parameters on quantitative uptake measures, such as standardized uptake value (SUV) and target-to-background ratio (TBR) has not been investigated extensively.ObjectiveThe goal of this study was to explore the effect of several data acquisition and image analysis parameters on quantification of vascular wall 18F-FDG uptake measures, in order to increase awareness of potential variability.MethodsThree whole-body emission scans and a low-dose CT scan were acquired 38, 60 and 90 minutes after injection of 18F-FDG in six rheumatoid arthritis patients with high cardiovascular risk profiles.Data acquisition (1 and 2) and image analysis (3, 4 and 5) parameters comprised:1. 18F-FDG uptake time, 2. SUV normalisation, 3. drawing regions/volumes of interest (ROI's/VOI's) according to: a. hot-spot (HS), b. whole-segment (WS) and c. most-diseased segment (MDS), 4. Background activity, 5. Image matrix/voxel size.Intraclass correlation coefficients (ICC's) and Bland Altman plots were used to assess agreement between these techniques and between observers. A linear mixed model was used to determine the association between uptake time and continuous outcome variables.Results1. Significantly higher TBRmax values were found at 90 minutes (1,57 95%CI 1,35-1,80) compared to 38 minutes (1,30 95%CI 1,21-1,39) (P = 0,024) 2. Normalising SUV for BW, LBM and BSA significantly influences average SUVmax (2,25 (±0,60) vs 1,67 (±0,37) vs 0,058 (±0,013)). 3. Intraclass correlation coefficients were high in all vascular segments when SUVmax HS was compared to SUVmax WS. SUVmax HS was consistently higher than SUVmax MDS in all vascular segments. 4. Blood pool activity significantly decreases in all (venous and arterial) segments over time, but does not differ between segments. 5. Image matrix/voxel size does not influence SUVmax.ConclusionQuantitative measures of vascular wall 18F-FDG uptake are affected mainly by changes in data acquisition parameters. Standardization of methodology needs to be considered when studying atherosclerosis and/or vasculitis.

Project description:The ability to detect and quantify macrophage accumulation can provide important diagnostic and prognostic information for atherosclerotic plaque. We have previously shown that LyP-1, a cyclic 9-amino acid peptide, binds to p32 proteins on activated macrophages, facilitating the visualization of atherosclerotic plaque with PET. Yet, the in vivo plaque accumulation of monomeric [(18)F]FBA-LyP-1 was low (0.31 ± 0.05%ID/g). To increase the avidity of LyP-1 constructs to p32, we synthesized a dendritic form of LyP-1 on solid phase using lysine as the core structural element. Imaging probes (FAM or 6-BAT) were conjugated to a lysine or cysteine on the dendrimer for optical and PET studies. The N-terminus of the dendrimer was further modified with an aminooxy group in order to conjugate LyP-1 and ARAL peptides bearing a ketone. Oxime ligation of peptides to both dendrimers resulted in (LyP-1)4- and (ARAL)4-dendrimers with optical (FAM) and PET probes (6-BAT). For PET-CT studies, (LyP-1)4- and (ARAL)4-dendrimer-6-BAT were labeled with (64)Cu (t1/2 = 12.7 h) and intravenously injected into the atherosclerotic (ApoE(-/-)) mice. After two hours of circulation, PET-CT coregistered images demonstrated greater uptake of the (LyP-1)4-dendrimer-(64)Cu than the (ARAL)4-dendrimer-(64)Cu in the aortic root and descending aorta. Ex vivo images and the biodistribution acquired at three hours after injection also demonstrated a significantly higher uptake of the (LyP-1)4-dendrimer-(64)Cu (1.1 ± 0.26%ID/g) than the (ARAL)4-dendrimer-(64)Cu (0.22 ± 0.05%ID/g) in the aorta. Similarly, subcutaneous injection of the LyP-1-dendrimeric carriers resulted in preferential accumulation in plaque-containing regions over 24 h. In the same model system, ex vivo fluorescence images within aortic plaque depict an increased accumulation and penetration of the (LyP-1)4-dendrimer-FAM as compared to the (ARAL)4-dendrimer-FAM. Taken together, the results suggest that the (LyP-1)4-dendrimer can be applied for in vivo PET imaging of plaque and that LyP-1 could be further exploited for the delivery of therapeutics with multivalent carriers or nanoparticles.

Dataset Information

Association between atherosclerotic cardiovascular disease risk score estimated by pooled cohort equation and coronary plaque burden as assessed by NaF-PET/CT.

Publications

Association between atherosclerotic cardiovascular disease risk score estimated by pooled cohort equation and coronary plaque burden as assessed by NaF-PET/CT.

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