Compartmental analysis of metabolism by13C magnetic resonance spectroscopy

Abstract

13C NMR, also called13C MRS, is used to track metabolic processes in vivo. Following the administration of molecules labeled with the nonradioactive carbon isotope13C, the isotope can be observed with MRS. If data are acquired while the13C levels in the tissue are changing, then it may be possible to determine absolute metabolic rates. For data that are acquired after13C levels in the tissue have stabilized, then relative rates of metabolism may be determined. The observations support the estimation of rates by fitting metabolic simulations to the data, using a formal procedure that includes the basic elements of an isotopic flow model: metabolic pools, rates, and substrate drivers. Model refinements, such as evaluation of metabolic compartments in samples that cannot be purified to a single biochemical state, can often be achieved by making multiple observations, each under conditions that emphasize one compartment more than the others. One example is measurements with different substrates, such as13C-acetate to emphasize glial metabolism, compared to13C-glucose to emphasize neuronal metabolism. Another is a measurement that contains more stimulated brain tissue compared to a measurement that contains less stimulated brain tissue, to assess unstimulated and stimulated metabolism. Sampling can be performed in vivo, in situ, ex vivo, and in cell cultures, and other conditions, each of which has its own limitations and advantages. This chapter is designed to provide a practical perspective on the acquisition and analysis of13C MRS data.