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An overview of ^sup 13^C nuclear magnetic resonance (NMR) spectroscopy methods and their applications in the study of the metabolism of brain cells in vitro and in the in vivo brain is presented as well as their implications for modern molecular imaging techniques. Various topics will be discussed, such as general properties of the ^sup 13^C NMR spectrum, ^sup 13^C NMR spectroscopy acquisition protocols, determination of fractional ^sup 13^C enrichment, ^sup 13^C(^sup 2^H) NMR methodologies, and the use of ^sup 13^C hyperpolarized substrates for NMR spectroscopy and imaging. Some illustrative applications are described, both in vitro and in vivo.
KEY WORDS: Magnetic resonance spectroscopy - Brain - Cells - Brain, metabolism -
Since the first ^sup 13^C nuclear magnetic resonance (NMK) spectroscopy metabolic stLicly of a living organism, describing the metabolism of ( 1-^sup 13^C) glucose by an eLikaryotic cell system,1 this techniqLie developed into a powerful method for metabolic research with cells, perfused organs, in vivo animals and humans. 2 4 In fact. ^sup 13^C NMR Spectroscopy allows to measure metabolic processes non-invasively as they proceed in their intracellular environment. It also provides unique information, not accessible from previously used radioactive, spectrophotometric or fluorimetric approaches, as it is based on measurement of unique physical properties specific to NMR, such as spin coupling patterns, isotopic shifts or magnetic relaxation times T^sub 1^ and T^sub 2^.
In 1^sup 13^C NMR spectroscopy, magnetic resonances from ^sup 13^C nuclei, the only stable isotope of carbon having a magnetic moment, are detected. With a natural abundance roughly of 1.1% of the total carbon and a magnetogyric ratio approximately one fourth ofthat of the proton, ^sup 13^C NMR spectroscopy is a relatively insensitive technique.5 However, natural abundance MC resonances from fatty acid chains of triglycerides are easily observed in most tissues and glycogen carbons can be detected in the liver and muscle of fed animals and humans.2, 3, 6 On the other hand, the use of substrates selectively enriched in ^sup 13^C in specific-positions provided a remarkable sensitivity improvement in the detection of other metabolites. This made it possible to follow in vivo and in vitro by ^sup 13^C NMR spectroscopy the activity of a large variety of metabolic pathways in cells, animals and humans. These include, amongst...