Molecular imaging in atherosclerosis

Abstract

Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat cardiovascular disease.

Assessing global cardiovascular molecular calcification with 18F-fluoride PET/CT: will this become a clinical reality and a challenge to CT calcification scoring?

“…For years it has been tried to image coronary lesions by either single photon emission computed tomography (SPECT) or PET. Except for a few promising reports [20,21], attempts to visualize the vulnerable plaque have on the whole been disappointing due to a series of limiting factors [1,2,22]. However, with the idea of measuring global molecular cardiovascular calcification conceptually years, perhaps decades, before it becomes macroscopically visible, things may change dramatically.…”

“…Functional imaging critically looking into each of these distinctive processes can provide insight into their formation, progression, vulnerability, and resulting atherothrombotic complications. The concept of the vulnerable coronary plaque, i.e., the soft, lipid-filled endothelial swelling with a fibrous cap that may disrupt and cause a cascade of thromboembolic processes leading to occlusion and acute myocardial infarction more often than narrow calcified stenoses, has led to a search for methods that can detect these culprit lesions in the coronary bed [2,17]. Further, it has served as a basis for the creation of a novel practice guideline for cardiovascular screening in the asymptomatic at-risk population.…”

“…In a review published in this journal [2], the targets and the radiopharmaceuticals with their targeting characteristics were classified into four major groups: (1) atherosclerotic lesion components (targets include foam cells, lipoproteins, lipids, endothelin); (2) inflammation (targeting metabolic glucose activity, macrophages and monocytes, neutrophils, monocytes and lymphocytes, lymphocytes); (3) thrombosis (targeting platelets, activated platelets, fibrins, etc. ); and (4) apoptosis.…”

“…The complex biology of atherosclerosis has been approached by functional imaging from multiple directions, each exploring the specific and distinctive etiopathogenetic mechanisms underlying its formation and progression as well as its subsequent complications [1][2][3][4][5]. In a review published in this journal [2], the targets and the radiopharmaceuticals with their targeting characteristics were classified into four major groups: (1) atherosclerotic lesion components (targets include foam cells, lipoproteins, lipids, endothelin); (2) inflammation (targeting metabolic glucose activity, macrophages and monocytes, neutrophils, monocytes and lymphocytes, lymphocytes); (3) thrombosis (targeting platelets, activated platelets, fibrins, etc.…”

After the Triumph of Cardiovascular Medicine Over Acute Myocardial Infarction at the End of the 20th Century - Can We Predict the Onset of Acute Coronary Syndrome? (Con) -

“…Therefore, currently there is not a specific tracer that can be used as a diagnostic tool to diagnose prospective AMI/ACS in patients. 18 It was a valuable discovery when acute plaque rupture was found to be the major cause of sudden coronary death. 20 From the examination of more than 800 cases of sudden coronary death at autopsy, Finn et al found that 55-60% of subjects had underlying plaque rupture as the etiology.…”