Assessing global coronary artery disease with NaF-PET/CT: Introducing the Alavi-Carlsen Calcification Score (ACCS)

Introduction: 1. Review the conventional methods in evaluating coronary artery disease (CAD) and discuss the utilization of molecular imaging in CAD. 2. Discuss the advantages of ¹⁸F-sodium fluoride (NaF) as a PET tracer in atherosclerosis imaging. 3. Introduce the Alavi-Carlsen Calcification Score (ACCS) as a method of global assessment of micro-calcification in CAD.

Methods: CAD is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the known major contributing disease process. Atherosclerosis is a complex and progressive process which can begin as early as in childhood with the development of fatty streaks, followed by molecular micro-calcification of atheromatous plaques, and gradually progressing to structural macro-calcification under the influence of the inflammatory mechanism, leading to the risk of plaque rupture and eventually vessel occlusion. Additionally, coronary artery calcification has been proven as an important independent predictor of CAD events. Therefore, it is of utmost importance to develop diagnostic methods that can identify micro-calcification of the vessels in the early stages. Over the past few decades, the evolution of imaging techniques has improved the evaluation of CAD. The most established non-invasive diagnostic imaging for identifying atherosclerosis is computed tomography (CT) using the coronary artery calcium score (CACS), a reliable metric for macro-calcification burden. Similarly, other conventional imaging modalities such as coronary computed tomographic angiography (CTA) and cardiac magnetic resonance imaging (MRI) have proven beneficial in detecting macro-calcification but are of limited ability to visualize micro-calcification in early stages of atherosclerosis. Invasive coronary angiography, which has been the gold standard for coronary atherosclerosis imaging, does not exhibit the ability for direct imaging of micro-calcification. In contrast, positron emission tomography (PET) molecular imaging is able to detect early-stage CAD with ¹⁸F-fluorodeoxyglucose (FDG) and NaF, markers of inflammation and micro-calcification, respectively.

Results: Previous studies of NaF have shown that its uptake is significantly correlated with the risk factors of CAD and the incidence of myocardial infarction. It has been demonstrated that coronary NaF uptake precedes macroscopic calcification and that there is no accumulation of NaF in the myocardium. The Alavi–Carlsen Calcification Score (ACCS) was introduced based on the concept of global disease assessment as applied to atherosclerosis imaging rather than focusing on individual plaques. The score is derived from measuring the total NaF uptake by segmenting the entire heart from the surrounding tissues and calculating the average standardized uptake value (SUVmean). Since the score is measured based on clearly delineated anatomical boundaries, it has less inter-rater variation. Furthermore, the implementation of artificial intelligence (AI)-based approaches in ACCS would ensure a fast and reliable method.

Conclusions: Global assessment of CAD using ACCS has the potential to detect and quantify burden of disease by reliably detecting molecular changes not apparent by other means. This represents a landmark approach, with implications for both the diagnosis and treatment of CAD.