Clinical imaging of cardiovascular inflammation

Abstract

Cardiovascular disease due to atherosclerosis is the number one cause of morbidity and mortality worldwide. In the past twenty years, compelling preclinical and clinical data have indicated that a maladaptive inflammatory response plays a crucial role in the development of atherosclerosis initiation and progression in the vasculature, all the way to the onset of life-threatening cardiovascular events. Furthermore, inflammation is key to heart and brain damage and healing after myocardial infarction or stroke. Recent evidence indicates that this interplay between the vasculature, organs target of ischemia and the immune system is mediated by the activation of hematopoietic organs (bone marrow and spleen). In this evolving landscape, non-invasive imaging is becoming more and more essential to support either mechanistic preclinical studies to investigate the role of inflammation in cardiovascular disease (CVD), or as a translational tool to quantify inflammation in the cardiovascular system and hematopoietic organs in patients. In this review paper, we will describe the clinical applications of non-invasive imaging to quantify inflammation in the vasculature, infarcted heart and brain, and hematopoietic organs in patients with cardiovascular disease, with specific focus on [18F]FDG PET and other novel inflammation-specific radiotracers. Furthermore, we will briefly describe the most recent clinical applications of other imaging techniques such as MRI, SPECT, CT, CEUS and OCT in this arena.

Figure 1.—

Overall overview of key organs and tissues involved in cardiovascular inflammation and atherogenesis, together with the most relevant PET tracers used to target these processes.

Figure 2.—

[¹⁸F]FDG imaging of cardiovascular immunometabolism. Higher [¹⁸F]FDG can be seen in the aortic arch, spleen and bone marrow of patients with acute coronary syndromes, with respect to controls (modified from Emami et al.). Prominent [¹⁸F]FDG uptake is also present in the infarcted heart after ischemia, indicating the presence of metabolically active inflammatory cells (modified from Marchesseau et al.).

Figure 3.—

[¹⁸F]NaF imaging of microcalcification. High [¹⁸F]NaF can be seen in concomitance with a calcified lesion in the femoral artery of a patient affected by PAD (modified from Chowhdury et al.). [¹⁸F]NaF uptake can also be detected in the infarcted myocardium (modified from Marchesseau et al.).

Figure 4.—

[68Ga]DOTATATE imaging of SSTR2 positive macrophages. [⁶⁸Ga]DOTATATE uptake is remarkable in a non-calcified coronary plaque (modified from Tarkin et al.). Prominent uptake can also be seen in the infarcted heart and brain (modified from Tarkin et al. and Vallee et al.).