Imaging Brain Metabolism

Hyperpolarized [1-13C]pyruvate ([1-13C]Pyr) has been used to assess metabolism in healthy and diseased states, focusing on the downstream labeling of lactate (Lac), bicarbonate and alanine. Although hyperpolarized [2-13C] Pyr, which retains the labeled carbon when Pyr is converted to acetyl-coenzyme A, has been used successfully to assess mitochondrial metabolism in the heart, the application of [2-13C]Pyr in the study of brain metabolism has been limited to date, with Lac being the only downstream metabolic product reported previously. In this study, sin- gle-time-point chemical shift imaging data were acquired from rat brain in vivo. [5-13C]Glutamate, [1-13C] acetylcarnitine and [1-13C]citrate were detected in addition to resonances from [2-13C]Pyr and [2-13C]Lac. Brain metabolism was further investigated by infusing dichloroacetate, which upregulates Pyr flux to acetyl-coenzyme A. After dichloroacetate administration, a 40% increase in [5-13C]glutamate, primarily from brain, and a trend to higher citrate were detected, whereas [1-13C]acetylcarnitine was increased in peripheral tissues. This study demonstrates, for the first time, that hyperpolarized [2-13C]Pyr can be used for the in vivo investigation of mitochondrial function and tricarboxylic acid cycle metabolism in brain. 

RSL locations

The Richard M. Lucas Center for Medical Imaging

1201 Welch Rd, Stanford CA 94305-5488

Stanford School of Medicine Technology & Innovation Park

3155 Porter Drive, Palo Alto, CA 94304