Metabolic and Molecular Imaging of Atherosclerosis and Venous Thromboembolism

Abstract

Metabolic and molecular imaging continues to advance our understanding of vascular disease pathophysiology. At present, ¹⁸F-FDG PET imaging is the most widely used clinical tool for metabolic and molecular imaging of atherosclerosis. However, novel nuclear tracers and intravascular optical near-infrared fluorescence imaging catheters are emerging to assess new biologic targets in vivo and in coronary arteries. This review highlights current metabolic and molecular imaging clinical and near-clinical applications within atherosclerosis and venous thromboembolism, and explores the potential for metabolic and molecular imaging to affect patient-level risk prediction and disease treatment.

Keywords: PET; atherosclerosis; molecular imaging; near infrared fluorescence; venous thromboembolism.

FIGURE 1.

Evidence of cardiosplenic axis in ACS patients. ¹⁸F-FDG uptake is significantly increased in aortic wall (left), bone marrow (middle), and spleen (right) in ACS patients compared with controls. (Reprinted with permission of Emami et al. (9).)

FIGURE 2.

¹⁸F-FDG PET/CT inflammation imaging in familial hypercholesterolemia patients. (A) ¹⁸F-FDG uptake is elevated in the aorta of familial hypercholesterolemia subjects (left) compared with controls (right), as quantified by significantly higher mean arterial target-to-background ratio. FH = familial hypercholesterolemia; TBR = target-to-background ratio. (Reprinted with permission from van Wijk et al. (11).)

FIGURE 3.

NIRF imaging of ICG deposition in human atheroma. (A) Aligned photo, fluorescence reflectance image (FRI), and long-view NIRF OCT fusion image of resected human carotid atheroma. Ninety minutes after intravenous ICG administration, elevated ICG signal (green-yellow) presents area of severe stenosis (arrowheads). NIRF OCT cross-sectional image at white dotted line shows thinned/absent fibrous cap (white dotted box), with corresponding high NIRF ICG signal. (B) High-magnification histology reveals complex plaque (top left, Movat’s Pentachrome [MP]) and surface ICG NIRF uptake (yellow, top right; fluorescein isothiocyanate [FITC autofluorescence (purple)]). ICG NIRF–positive areas demonstrate endothelial barrier disruption (CD31; arrows) and macrophage infiltration (CD68). ICA = internal carotid artery; L = lumen. (Reprinted with permission from Verjans et al. (21).)

FIGURE 4.

¹⁸F-FDG PET/CT imaging of recurrent VTE. (A) Mouse model illustrating day-14 DVT and religation of jugular vein to create recurrent DVT mouse model used in ¹⁸F-FDG PET imaging. Histologic staining with hematoxylin and eosin (B), Carstairs (C), and Masson’s Trichrome (D) of resected day-2 recurrent DVT (black dotted line) overlying day-16 DVT (blue dotted line) show red blood cell and fibrin-rich areas in recurrent DVT (red and yellow area in B–D) and collagen-rich zones in older primary DVT (blue areas in C and D). Immunostaining for neutrophils (E) and macrophages (F) highlight differences between recurrent DVT and older DVT. ¹⁸F-FDG PET/CT images (G–I) of recurrent and primary DVT show increased ¹⁸F-FDG uptake in recurrent DVT (J–L). Yellow arrows = recurrent DVT; white arrows = primary day 16 DVT. (Reprinted with permission from Hara et al. (28).)