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Quantifying normal human brain metabolism using hyperpolarized [1-13C]pyruvate and magnetic resonance imaging.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Grist, James T 
McLean, Mary A 
Schulte, Rolf F 
Deen, Surrin S 

Abstract

Hyperpolarized 13C Magnetic Resonance Imaging (13C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1-13C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13C images demonstrated 13C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (kPL) for exchange of the hyperpolarized 13C label between [1-13C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s-1 and the apparent rate constant (kPB) for the irreversible flux of [1-13C]pyruvate to [13C]bicarbonate was 0.002 ± 0.002 s-1. Imaging also revealed that [1-13C]pyruvate, [1-13C]lactate and [13C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1-13C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.

Description

Keywords

Brain, Carbon-13, Hyperpolarized, MRI, Metabolism, Pyruvate, Adult, Brain, Carbon Isotopes, Female, Humans, Magnetic Resonance Imaging, Male, Neuroimaging, Pyruvic Acid

Journal Title

Neuroimage

Conference Name

Journal ISSN

1053-8119
1095-9572

Volume Title

189

Publisher

Elsevier BV
Sponsorship
MRC (1508766)
Cancer Research Uk (None)
Cancer Research Uk (None)
Evelyn Trust (project ref 15/37)
Multiple Sclerosis Society (35)
MRC, BBSRC, CRUK, NIHR, EPSRC, ACT, ECMC, Evelyn Trust, MS society,