Tandem 5: MR-based Cardiovascular Metabolic Imaging

Short Summary:

We develop and validate accelerated Magnetic Resonance imaging as a tool for mapping substrate and lipid content in experimental models and patients with metabolic syndrome. Currently, we test if the diagnosis of metabolic derangements can serve as an early marker of prospective cardiovascular disease, enabling to identify metabolic alterations before the onset of functional impairment.

Scope:

Cardiovascular diseases remain the major cause of mortality in the Western world. Although diagnostic and therapeutic advances have led to an overall reduction in mortality, direct and indirect cost of cardiovascular diseases continue to rise as a result of an aging population and life style changes. In this regard, obesity and physical inactivity have become major issues frequently resulting in metabolic abnormalities collectively referred to as the cardiometabolic syndrome (Eckel et al., 2010). Patients with metabolic syndrome carry a more than two-fold chance of developing cardiovascular disease relative to age-matched controls (Grundy et al., 2012). To this end, it is of great importance to identify metabolic alterations before the onset of functional impairment. Important mechanism relate to lipotoxicity i.e. accumulation of fatty acids in the heart and liver (Targher et al., 2010) and to changes of substrate uptake and conversion (Schroeder et al., 2011).

Specific Aims:

The overall aim of the project is to develop and validate accelerated Magnetic Resonance spectroscopic imaging as a tool for mapping substrate and lipid content in patients with metabolic syndrome. It is a particular purpose to test if the diagnosis of metabolic derangements can serve as an early marker of prospective cardiovascular disease in conjunction with visceral fat volume and standard functional measurements. Along with efforts to translate hyperpolarized Magnetic Resonance imaging from animal to human application, investigation of metabolic changes in obese animal models will be followed to unravel correlations of metabolic and functional impairment.

Molecular imaging techniques used:

Magnetic Resonance Spectroscopy, Hyperpolarized Magnetic Resonance Imaging.

In vivo metabolic imaging of a rat heart: A = Pyruvate, B = Lactate, C = Bicarbonate

Added value of KFSP for this specific tandem project:

The present project requires considerable efforts in Magnetic Resonance pulse sequence development and image reconstruction techniques to translate current prototype developments into packages applicable to patients. Simultaneously, clinical expertise is required to implement the techniques for patient studies including the development of comprehensive imaging protocols and computation of metabolic and functional indices. Close interaction between a physicist and a clinician is essential. Joint supervision will ensure rapid translation of methodological developments into clinical testing and hence will expedite the overall process of making diagnostic tools available.

References