Cardiovascular molecular imaging: the road ahead

Abstract

Despite significant advancements in medical and device-based therapies, cardiovascular disease remains the number one cause of death in the United States. Early detection of atherosclerosis, prevention of myocardial infarction and sudden cardiac death, and modulation of adverse ventricular remodeling still remain elusive goals. Molecular imaging focuses on identifying critical cellular and molecular targets and therefore plays an integral role in understanding these biologic processes in vivo. Because many imaging targets are upregulated before irreversible tissue damage occurs, early detection could ultimately lead to development of novel, preventive therapeutic strategies. This review addresses recent work on radionuclide imaging of cardiovascular inflammation, infection, and infarct healing. We further discuss opportunities provided by multimodality approaches such as PET/MRI and PET/optical imaging.

Figure 1. Imaging and the ischemic cascade

Schematic representation of disease progression. Plaque rupture and coronary thrombosis represent the inflection point. A) PET/CT of VCAM-1 expression (4); B) PET/CT of macrophages (5); C) SPECT/CT of MMP (7); D) intracoronary optical coherence tomography(courtesy of Kevin Croce); E) thrombotic occlusion of a coronary artery(reproduced with permission from British Medical Journal publishing group); F) tagging MRI (own data); G) angina pectoris (reproduced with permission from American Medical Association); H) late gadolinium enhancement MRI showing myocardial infarction (own data).

Figure 2. Targeted imaging of atherosclerosis

(A) ¹⁸F-4V PET/CT of VCAM-1 expression (4). Higher uptake is seen in ApoE^−/− mice as compared to statin-treated mice (B). (C) Nanoparticle PET/CT of macrophages (5). (D) MRI with pseudocolored T2 signal intensity which decreased due to accumulation of iron oxide nanoparticles.

Figure 3. Vascular inflammation, infection, and infarct healing

(A) Macrophage-targeted PET/CT of inflammation in aortic aneurysm with ¹⁸F-CLIO (12). Dotted circle outlines the aneurysm in the ascending aorta. (B) PET/CT of S. aureus endocarditic vegetation (arrow) in mice with ⁶⁴Cu-ProT(14). (C) Hybrid PET/MRI of murine post-infarction inflammation with a macrophage-targeted ⁶⁴Cu-labeled nanoparticle (own unpublished data). The infarct area is detected by late gadolinium enhancement on MRI (insert, arrows).