Molecular imaging in cardiovascular disease: Which methods, which diseases?

Abstract

Techniques for in vivo assessment of disease-related molecular changes are being developed for all forms of non-invasive cardiovascular imaging. The ability to evaluate tissue molecular or cellular phenotype in patients has the potential to not only improve diagnostic capabilities but to enhance clinical care either by detecting disease at an earlier stage when it is more amenable to therapy, or by guiding most appropriate therapies. These new techniques also can be used in research programs in order to characterize pathophysiology and as a surrogate endpoint for therapeutic efficacy. The most common approach for molecular imaging involves the creation of novel-targeted contrast agents that are designed so that their kinetic properties are different in disease tissues. The main focus of this review is not to describe all the different molecular imaging approaches that have been developed, but rather to describe the status of the field and highlight some of the clinical and research applications that molecular imaging will likely provide meaningful benefit. Specific target areas include assessment of atherosclerotic disease, tissue ischemia, and ventricular and vascular remodeling.

Figure 1

Potential roles of molecular imaging in science and clinical medicine.

Figure 2

Schematic depiction of potential targets for imaging early, mid-stage, or advanced “vulnerable” atherosclerosis.

Figure 3

Images of the aorta from a murine model of age-dependent atherosclerosis at (A) 10 weeks and (B) 40 weeks of age demonstrating time-dependent increase in plaque by oil red-O (ORO) staining of the thoracic aorta; increased macrophage (Mac-1) accumulation in the neointima, and increased distribution of CEU molecular imaging signal for VCAM-1. (C) Quantitative data for VCAM-1 and P-selectin CEU signal demonstrating the ability to detect very early ECAM expression at disease initiation. Reproduced from Kaufmann et al.

Figure 4

Images in the horizontal and vertical long-axis planes from a patient with recent anterior MI showing corresponding region of infarct by delayed-enhanced gadolinium MRI (A, D), regional hypoperfusion by ¹³N-ammonia PET (B, E), and increased PET signal from ¹⁸F-labeled RGD peptide targeted to α_vβ₃ integrin (C, F). Reproduced with permission from Makowski et al.

Figure 5

Potential roles of molecular imaging in stem cell therapy.

Figure 6

(A) Contrast CT (top row), ¹³N-NH₃ PET perfusion (middle row), and molecular imaging of AT1R images using ¹¹C-KR31173 PET in a pig following myocardial infarction. Relative activity of AT1R in the infarct zone is greater than relative perfusion and is also increased in the right ventricle. (B) Fused transaxial ¹¹C-KR31173 PET/CT images in a normal subject through the mid-cardiac region demonstrating homogeneous myocardial uptake of AT1R at baseline (left) at baseline which is reduced after administration of an angiotensin receptor blocker (olmesartan).