Journal
NEUROIMAGE
Volume 189, Issue -, Pages 171-179Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2019.01.027
Keywords
Metabolism; Hyperpolarized; MRI; Carbon-13; Brain; Pyruvate
Funding
- Wellcome Trust
- Cancer Research UK (CRUK) [C19212/A16628, C19212/A911376, C197/A16465]
- CRUK Cambridge Centre
- National Institute of Health Research-Cambridge Biomedical Research Centre
- Medical Research Council
- CRUK/Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester
- Addenbrooke's Charitable Trust
- Cambridge Experimental Cancer Medicine Centre
- Evelyn Trust
- Multiple Sclerosis Society
- National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]
- National Institute for Health Research [Mark Foundation Institute for Integrative Cancer Medicine at the University of Cambridge]
- Austrian Science Fund (FWF) [J4025] Funding Source: Austrian Science Fund (FWF)
- MRC [G0601490] Funding Source: UKRI
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Hyperpolarized C-13 Magnetic Resonance Imaging (C-13-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-C-13]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of C-13 images demonstrated C-13-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 (k(PL)) for exchange of the hyperpolarized C-13 label between [1-C-13]pyruvate and the endogenous lactate pool was 0.012 +/- 0.006 s(-1) and the apparent rate constant (k(PB)) for the irreversible flux of [1-C-1(3)]pyruvate to [C-13]bicarbonate was 0.002 +/- 0.002 s(-1). Imaging also revealed that [1-C-13]pyruvate, [1-C-13] lactate and [C-13]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1-C-13]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.
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