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.
Highlights
Cerebral metabolism is important for normal brain function and becomes deranged in a number of pathological processes, such as inflammation, infection, ischemia, traumatic brain injury and in tumors (Jalloh et al, 2015; Mathur et al, 2014; Matz et al, 2006). 18F-fluorodeoxyglucose (FDG) uptake, detected using positron emission tomography (PET), is one approach to imaging this cerebral metabolism in patients
Despite the sensitivity of PET, the signal acquired from 18F-FDG represents flux in only part of the glycolytic pathway measuring a combination of delivery to the tissue, uptake by glucose transporters and subsequent phosphorylation in the reaction catalyzed by the glycolytic enzyme, hexokinase
Lactate and pyruvate all play a role as cerebral energy sources
Summary
Cerebral metabolism is important for normal brain function and becomes deranged in a number of pathological processes, such as inflammation, infection, ischemia, traumatic brain injury and in tumors (Jalloh et al, 2015; Mathur et al, 2014; Matz et al, 2006). 18F-fluorodeoxyglucose (FDG) uptake, detected using positron emission tomography (PET), is one approach to imaging this cerebral metabolism in patients. Cerebral metabolism is important for normal brain function and becomes deranged in a number of pathological processes, such as inflammation, infection, ischemia, traumatic brain injury and in tumors (Jalloh et al, 2015; Mathur et al, 2014; Matz et al, 2006). The work presented here uses a new imaging method to investigate cerebral metabolism of pyruvate, a breakdown product of glucose. The metabolic shift from mitochondrial oxidative metabolism to glycolysis and lactate formation occurs in a number of pathological processes, such as ischemia, inflammation, and in tumors (Jalloh et al, 2015; Mathur et al, 2014; Matz et al, 2006). Alternative non-invasive methods to image lactate would be valuable to monitor glycolysis in vivo
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
