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

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.

Comparison between 8‐ and 32‐channel phased‐array receive coils for in vivo hyperpolarized 13C imaging of the human brain

“…Following the discovery of dissolution dynamic nuclear polarization (d‐DNP) techniques, the field of hyperpolarized 13 C imaging has enabled diverse applications for non‐invasively probing real‐time metabolism in vivo . In the context of clinical translation, validating the utility of these applications is key to understanding their potential diagnostic impact.…”

“…Following the discovery of dissolution dynamic nuclear polarization (d-DNP) techniques, 1 the field of hyperpolarized 13 C imaging has enabled diverse applications for non-invasively probing real-time metabolism in vivo. [2][3][4] In the context of clinical translation, validating the utility of these applications is key to understanding their potential diagnostic impact. While d-DNP affords appreciable signal enhancement by means of spin polarization, metabolites downstream of the substrate can fall within a low SNR regime, given their enzyme-mediated conversion, signal decay from T 1 and radiofrequency (RF) use, and label/molecule-dependent T 1 -shortening effects.…”

Three‐dimensional accelerated acquisition for hyperpolarized 13C MR with blipped stack‐of‐spirals and conjugate‐gradient SENSE

“…This has been demonstrated in multiple recent patient studies. [1][2][3][4][5][6][7][8][9][10] However, because of the short-lived nature of the hyperpolarized substrate, 11 many sequence designs for human imaging end up sacrificing either resolution or coverage in one or more dimensions for the sake of encoding the remaining multidimensional space within the narrow time window.…”

Glycolytic metabolism of pathogenic T cells enables early detection of GvHD by13C-MRI

“…As a result, FDG-PET is unable to distinguish increases in glycolytic flux from increases in oxidative phosphorylation 24 . To overcome this limitation 13 C-labeled metabolites detected by spectroscopic magnetic resonance imaging (MRI) have become increasingly used for functional imaging primarily in the setting of malignancy [25][26][27][28][29][30] , and more recently in other inflammatory conditions 31,32 . Ex vivo dynamic nuclear hyperpolarization (DNP) of the 13 C-pyruvate tracer prior to infusion has improved the sensitivity of its MRI detection to allow real-time spectroscopic measurement of in vivo glycolytic activity within tissues in preclinical and clinical studies 33,34 .…”