Basic Science for Clinicians Cardiovascular Molecular Imaging Focus on Clinical Translation

The past few decades have seen an explosion in the knowledge of the molecular basis of cardiovascular diseases owing to rapid advances in molecular biology research. An improved understanding of disease pathogenesis at the genomic, transcriptional, and proteomic levels has led to the discovery of promising experimental strategies for the prevention, diagnosis, and treatment of cardiovascular disease. Unfortunately, only a minute number of these strategies have survived the rigors of preclinical and clinical trials to become therapeutically useful. Furthermore, even these successful strategies must endure a prolonged process of translation from bench to bedside, partially owing to the lack of tools to directly interrogate the molecular events in patients. The strong impetus to develop noninvasive imaging techniques to visualize molecular changes in patients has given birth to the field of molecular imaging. 1,2 Molecular imaging has its roots in nuclear medicine, in which radiolabeled imaging probes are injected into living subjects to assess the functionality of different organ systems. Unlike conventional diagnostic imaging techniques (eg, radiography and computed tomography [CT]) that delineate the anatomy of the cardiovascular system (eg, coronary luminal diameter), molecular imaging techniques have been designed and validated to study much smaller-scale molecular events (eg, gene expression) that may underlie disease processes. The complexity of molecular imaging lies in the requirement for molecular targeting, the design of which requires a solid understanding of the pharmacokinetics of the imaging probe and how it interacts with the molecular target. When the target is proven to be a biomarker, molecular imaging becomes a valuable tool for detecting disease before its clinical manifestation, stratifying disease severity, predicting disease progression, monitoring treatment efficacy, and prognosticating disease. These challenges must be met before the true potential of personalized medicine can be fully realized. 3 Significant advances have been made in molecular imaging to make it a clinical reality in many areas. Instrumental in its development has been the advancement of small-animal imaging technologies over the past 2 decades, including fluorescence imaging (FI), bioluminescence imaging (BLI), ultrasound, micro-positron emission tomography (microPET), micro–single photon emission computed tomography (microSPECT), high-field small animal magnetic resonance imaging (MRI), and micro–computed tomography (microCT; Figure 1A). A parallel development has been the construction of sophisticated imaging probes with high specificity for various molecular targets. The use of these imaging systems and probes has facilitated the validation of molecular imaging techniques in animal models. Ongoing translation of these techniques into the clinical arena is being achieved by use of either clinical versions of small-animal scanners or special imaging platforms specifically developed for clinical translation. A wide range of exciting cardiovascular molecular imaging applications have now been developed and reviewed previously.1,4,5 After a brief overview of the fundamentals of molecular imaging approaches, the present review will focus on the latest advances in the areas of atherosclerosis, heart failure, and stem cell therapy. The article will conclude with discussions on the future prospects of molecular imaging in the clinical arena, as well as future directions that will shape molecular imaging in the postgenomics era.