Hyperpolarized Magnetic Resonance Spectroscopy for Metabolic Imaging of the Diseased Heart

There are about 1.8 million people in the UK with diabetes and 3 million cases are predicted by 2010. Diabetics are at high risk of heart disease because the way they make energy from foods, such as fats and sugars, is faulty. Understanding these faults is important to find new ways to treat people with diabetes.
Magnetic Resonance Imaging (MRI) is a method which can see inside living things and can help us to see how we change the food we eat into energy. The big problem with MRI is that the amount of signal we can see can be very small. In 2003, a new method of imaging which gives more signal in MRI was invented. This new method provides greater than 10,000 times more signal for a short period of time. This method is a tool which can help us answer our questions about why some people make energy from food in a faulty way.
Our aim is to develop this new method to help us understand how normal hearts work and what goes wrong in diabetic hearts.

Molecular imaging, in which imaging technology is coupled with molecular probes to detect disease-specific markers, will transform our approach to disease detection and treatment. Recently developed methods that can hyperpolarize molecular tracers [Dynamic Nuclear Polarization (DNP) technique] result in greater than 10,000 fold increases in the sensitivity of Magnetic Resonance Spectroscopy (MRS) for metabolic imaging. The aim of this project is to develop further this technique to study initial rates of metabolism in the healthy rat heart and in a model of type-1 diabetes. Primarily the rates of pyruvate metabolism through key metabolic enzymes, such as pyruvate dehydrogenase, in the normal heart will be made. Through technical developments, this project will also allow the study of other important metabolic molecules, such as acetate and alpha-ketogluterate. Understanding of initial metabolic rates of key molecules will provide insight into disease identification, progression and treatment that will provide new information to basic biochemical science. The techniques developed could eventually be transferred to the clinical environment.