The vast amount of genomic information becoming available on many organisms has transformed the way we study living systems.  We can now aim to understand how component parts collaborate to create complex biological systems.

This integrative approach requires the observation of molecular functions in the intact system and molecular imaging methods can visualize and quantify such processes.  Magnetic resonance spectroscopy (MRS) can be used to observe metabolic events in intact tissues non-invasively and the method has been widely used to study metabolism in whole organisms including man in normal and clinical situations.  While the information content of the measurement is in principle high, its low sensitivity is a limitation and several other imaging approaches have been developed that provide molecular information at various levels of resolution.  In addition to the study of fundamental biological processes, developments in molecular imaging provide a link to clinical research since most disease processes have a molecular basis.

Current Research Programme

Until 1996 I led a wide-ranging research programme aimed at defining molecular physiological events in human disease and relating these to energetic, control and adaptive functions of the cell using MRS and biochemical approaches.  Between 1996 and 2003, while I was seconded to the Medical Research Council, Professor Kieran Clarke became Director of the British Heart Foundation Magnetic Resonance Research Group (later renamed the Cardiac Metabolism Research Group) and I maintained a research interest mainly in cardiac energetics and specifically on the effect of diabetes and insulin resistance on the heart.

Currently my research at Oxford focuses on two areas:

• The use of stem cells for cardiac repair and the effect of diabetes on cardiac energetics (interacting with Kieran Clarke’s Cardiac Metabolism Research Group).
• I have introduced a programme on Dynamic Nuclear Polarisation with the support and collaboration of GE Healthcare.  A fundamental limitation of magnetic resonance is its low sensitivity, but GE Healthcare scientists have recently developed a practical method to enhance nuclear spin polarisation such that 10,000-fold gains in sensitivity can be achieved, in molecules with in vivo stability of approximately 30 seconds to one minute.  This has enabled visualization of ¹³C-labelled cellular metabolites in vivo and, more importantly, their enzymatic transformation into other species.  This is an important development that could revolutionise spectroscopy using MR. 

We have been selected by GE-Healthcare as one of the three academic sites where this new technique will be developed for specific metabolic studies in vivo.  The aim of the Oxford group will be to investigate the initial rapid metabolism of polarised ¹³C pyruvate, acetate and other metabolites in normal and diabetic and failing rat hearts in vivo.  The study should provide a new approach to the development of spatially resolved kinetic models for oxidative and glycolytic metabolism in normal and diseased rodent hearts and potentially could result in the use of hyperpolarised ¹³C MRS in clinical research and diagnosis.

The work on hyperpolarised ¹³C is likely to open up a completely new approach in metabolic and molecular imaging and could in principle become a clinical tool that may in the long run compete with positron emission tomography (PET).

A research programme which I lead in Singapore on bioimaging and metabolic medicine will be complementary to the work in Oxford; new techniques and disease models developed there will have implications for our studies in Oxford (where many of the studies proposed would not at this stage be possible).  An important part of the research in both locations is that the results will be translatable to clinical investigations of heart disease and diabetes.

Further information can be found at http://www.physiol.ox.ac.uk/Research_Groups/Cardiac_Metabolism/

George Radda