Recent advances in metabolic imaging

Abstract

Abnormalities in myocardial substrate metabolism play a central role in the manifestations of most forms of cardiac disease such as ischemic heart disease, heart failure, hypertensive heart disease, and the cardiomyopathy due to either obesity or diabetes mellitus. Their importance is exemplified by both the development of numerous imaging tools designed to detect the specific metabolic perturbations or signatures related to these different diseases, and the vigorous efforts in drug discovery/development targeting various aspects of myocardial metabolism. Since the prior review in 2005, we have gained new insights into how perturbations in myocardial metabolism contribute to various forms of cardiac disease. For example, the application of advanced molecular biologic techniques and the development of elegant genetic models have highlighted the pleiotropic actions of cellular metabolism on energy transfer, signal transduction, cardiac growth, gene expression, and viability. In parallel, there have been significant advances in instrumentation, radiopharmaceutical design, and small animal imaging, which now permit a near completion of the translational pathway linking in-vitro measurements of metabolism with the human condition. In this review, most of the key advances in metabolic imaging will be described, their contribution to cardiovascular research highlighted, and potential new clinical applications proposed.

Introduction

It has long been recognized that abnormalities in myocardial substrate metabolism play a central role in the manifestations of most forms of cardiac disease such as ischemic heart disease, heart failure, hypertensive heart disease, and the cardiomyopathy due to either obesity or diabetes mellitus. Indeed, vigorous efforts in drug discovery/development are targeting various aspects of myocardial metabolism such as with the partial fatty acid (FA) oxidation inhibitors and the glucagon-like peptide-1 agonists for the treatment of angina and heart failure, respectively. Further reflecting this recognition has been the development of numerous imaging tools designed to detect the specific metabolic perturbations or signatures related to these different diseases such as positron emission tomography (PET) using ¹⁸F-fluorodeoxyglucose (FDG) to measure myocardial glucose metabolism, single photon emission computed tomography (SPECT) using ¹²³I-methyl iodophenyl-pentadecanoic acid (BMIPP) to assess myocardial FA metabolism, and phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) to measure cardiac energetics. In the prior review in 2005 were discussed the relative strengths and weaknesses of the various approaches to image myocardial metabolism, their application in delineating disease pathogenesis in both experimental models and in humans, and their potential clinical application. Since then we have gained new insights into how perturbations in myocardial metabolism contribute to various forms of cardiac disease. Our understanding of myocardial metabolism has benefitted tremendously from the application of advanced molecular biologic techniques such as genomics, metabolomics, and proteomics. In addition, the development of elegant genetic models to characterize specific metabolic pathways permits exquisite delineation of the role of these pathways and their contribution to cardiac disease. The application of these techniques has highlighted the pleiotropic actions of cellular metabolism on energy transfer, signal transduction, cardiac growth, gene expression, and viability. In parallel, there have been significant advances in both instrumentation and radiopharmaceutical design. Improvements in small animal imaging now permit near completion of the translational pathway linking in-vitro measurements of metabolism with the human condition. In total, these advances have further ensconced metabolic imaging as a necessary tool to further our understanding of various forms of cardiovascular disease and potentially improve the care of the cardiac patient beyond its current use to detect viable myocardium. In this review, many of the key advances in metabolic imaging will be described, their contribution to cardiovascular research highlighted, and potential new clinical applications proposed.