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Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC)1 and carotid intimal medial thickness (C-IMT)2 provide information about the burden of disease. However, despite multiple validation studies of CAC3–5, and C-IMT2,6, these modalities do not accurately assess plaque characteristics7,8, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events9–13.
[18F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism14,15. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity16, an important source of cellular inflammation in vessel walls. More recently, we17,18 and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries9,16,19,20. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors21,22 and is also highly associated with overall burden of atherosclerosis23. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy24 as well as longer term therapeutic lifestyle changes (16 months)25.
The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is calculated by dividing the arterial SUV by the venous blood pool SUV. This method has shown to represent a stable, reproducible phenotype over time, has a high sensitivity for detection of vascular inflammation, and also has high inter-and intra-reader reliability26. Here we present our methodology for patient preparation, image acquisition, and quantification of atherosclerotic plaque activity and vascular inflammation using SUV, TBR, and a global parameter called the metabolic volumetric product (MVP). These approaches may be applied to assess vascular inflammation in various study samples of interest in a consistent fashion as we have shown in several prior publications9,20,27,28
The table below shows various methods of determining outcomes for atherosclerotic plaque activity and vascular inflammation detected by FDG-PET/CT in a single patient with psoriasis.
|Arterial Segment (number of slices)||SUVmean (SD)||TBR (SD)||MVP (SD)||GIB(SD)|
|Ascending Aorta (n=8)||1.43 (0.24)||1.31 (0.18)||5.68 (3.08)||53.99 (19.50)|
|Aortic Arch (n=5)||1.38 (0.25)||1.30 (0.22)||8.88 (4.94)||59.85 (18.66)|
|Descending Thoracic Aorta (n=20)||1.42 (0.20)||1.29 (0.19)||3.11 (0.98)||125.66 (53.11)|
|Suprarenal Abdominal Aorta (n=29)||1.40 (0.19)||1.26 (0.17)||2.37 (0.66)||50.75 (17.64)|
|Infrarenal Abdominal Aorta (n=26)||1.38 (0.21)||1.20 (0.16)||1.72 (0.54)||45.80 (10.86)|
The methodology presented here is straightforward to perform, and can yield useful information regarding atherosclerotic plaque activity and vascular inflammation in clinically significant arterial beds. There are some important features of this analysis approach which warrant emphasis: 1) We use a high-quality PET/CT scanner which has 16 detector rows and with time of flight capability; 2) We utilize two experienced observers blinded to the clinical information to perform measurements to ensure consistency of the quantitative data; 3) We describe concurrently four outcomes of quantification which are each informative. We recommend measurement of at least arterial mean SUV and venous blood mean SUV so that TBR can be estimated. We believe that MVP, a novel quantitative parameter, will also be an important determinant of atherosclerotic plaque activity and vascular inflammation to obtain, as it provides global quantification of disease burden by incorporating structural and molecular measurements. SUV and TBR do not account for the structural changes observed in atherosclerotic vascular diseases, whereas MVP does. Furthermore, MVP allows for summation of multiple measurements obtained from a vessel of interest for purposes of global assessment.
PET/CT is ideally suited for assessment of the short and long term effects of therapeutic modulation of these outcomes given its high sensitivity, high contrast resolution, quantitative nature, and ability to provide combined metabolic and anatomical information. Future studies should examine the effects of standard and novel treatments beyond statin therapy upon vascular inflammation as measured by PET/CT, as well as upon other disease states associated with excess atherosclerosis such as metabolic syndrome, rheumatoid arthritis, and diabetes mellitus, so as to advance field of non-invasive detection, characterization, and treatment of the atherosclerosis plaque.
The video component of this article can be found at http://www.jove.com/video/3777/
No conflicts of interest declared.