Myocyte Metabolic Imaging with Hyperpolarised MRI

Abstract

Magnetic Resonance is traditionally considered an inherently insensitive technique. This insensitivity arises due to the fact that the nuclear polarisation, the population difference between nuclear spin states, is very close to zero for samples at physiological temperatures for any magnetic field that can be created on earth. This fact serves to make the detection of biochemically pertinent compounds exceptionally challenging, as their concentration in vivo is typically millimolar or below. By exploiting either several nuclear processes or millikelvin temperatures, NMR-visible nuclei can be “pumped” out of what would be their room-temperature thermal equilibrium population distributions, becoming “hyperpolarised”. If subject to a step change in temperature and subsequently introduced to a living system, the large increase in the signal-to-noise ratio of magnetic resonance experiments generated by hyperpolarisation techniques enables the otherwise invisible molecular behaviour of labelled probes to be directly measured by magnetic resonance. Hyperpolarisation techniques therefore allow the in vivo spatial monitoring of perfusion and metabolism in the heart. In particular, there is a large and growing body of work that has investigated cardiac central metabolism through the use of hyperpolarised sodium [1-¹³C]pyruvate and [2-¹³C]pyruvate, which together can rapidly quantify fluxes through the majority of the the citric acid cycle, including the rates k _{Pyruvate→ Lactate} and k _{Pyruvate→Acetyl-CoA}, which are both profoundly altered in heart failure, hypertrophy, and during cardiac ischaemia. This chapter reviews the physical basis of the techniques (and hence the potential challenges in using them), before discussing the myriad array of molecular probes that have been proposed, and their potential utility in understanding both the basic physiology of the heart, and how it is altered in disease.