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Hyperpolarized [1-13C]pyruvate enables direct in vivo assessment of real-time liver enzymatic activities by 13C magnetic resonance. However, the technique usually requires the injection of a highly supraphysiological dose of pyruvate. We herein demonstrate that liver metabolism can be measured in vivo with hyperpolarized [1-13C]pyruvate administered at two- to three-fold the basal plasma concentration. The flux through pyruvate dehydrogenase, assessed by 13C-labeling of bicarbonate in the fed condition, was found to be saturated or partially inhibited by supraphysiological doses of hyperpolarized [1-13C]pyruvate. The [13C]bicarbonate signal detected in the liver of fasted rats nearly vanished after treatment with a phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, indicating that the signal originates from the flux through PEPCK. In addition, the normalized [13C]bicarbonate signal in fasted untreated animals is dose independent across a 10-fold range, highlighting that PEPCK and pyruvate carboxylase are not saturated and that hepatic gluconeogenesis can be directly probed in vivo with hyperpolarized [1-13C]pyruvate. Can et al. demonstrate the ability to use hyperpolarized [1-13C]pyruvate at nearphysiological concentrations to directly assess liver enzymatic activities by 13C magnetic resonance. While in the fed state, the normalized [13C]bicarbonate signal produced from hyperpolarized [1-13C]pyruvate derives from PDH activity, which is saturated at supraphysiological doses, it results from PEPCK in the fasted state and is dose-independent, allowing non-invasive in vivo detection of hepatic gluconeogenesis." [ABSTRACT FROM AUTHOR]

Brain cells depend on the availability of glucose for energy metabolism. Glucose transport to the brain can be assessed by utilizing plasma levels to measure brain glucose concentrations. Direct measurement by rapid-freezing in vitro is only possible in animals and not in humans. However, NMR spectroscopy has proven its ability to assess the concentration of several metabolites in living tissue. This method allows direct measurement of brain glucose concentrations and the possibility of examining glucose transport control in human brain in vivo appears promising.

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) allow the chemical analysis of physiological processes in vivo and provide powerful tools in the life sciences and for clinical diagnostics. Excellent homogeneity of the static B0 magnetic field over the object of interest is essential for achieving high‐quality spectral results and quantitative metabolic measurements. The experimental minimization of B0 variation is performed in a process called B0 shimming. In this article, we summarize the concepts of B0 field shimming using spherical harmonic shimming techniques, specific strategies for B0 homogenization and crucial factors to consider for implementation and use in both brain and body. In addition, experts' recommendations are provided for minimum requirements for B0 shim hardware and evaluation criteria for the primary outcome of adequate B0 shimming for MRS and MRSI, such as the water spectroscopic linewidth. [ABSTRACT FROM AUTHOR]

In vivo MRS is a non‐invasive measurement technique used not only in humans, but also in animal models using high‐field magnets. MRS enables the measurement of metabolite concentrations as well as metabolic rates and their modifications in healthy animals and disease models. Such data open the way to a deeper understanding of the underlying biochemistry, related disturbances and mechanisms taking place during or prior to symptoms and tissue changes. In this work, we focus on the main preclinical 1H, 31P and 13C MRS approaches to study brain metabolism in rodent models, with the aim of providing general experts' consensus recommendations (animal models, anesthesia, data acquisition protocols). An overview of the main practical differences in preclinical compared with clinical MRS studies is presented, as well as the additional biochemical information that can be obtained in animal models in terms of metabolite concentrations and metabolic flux measurements. The properties of high‐field preclinical MRS and the technical limitations are also described. [ABSTRACT FROM AUTHOR]

Brain metabolism evolves rapidly during early post‐natal development in the rat. While changes in amino acids, energy metabolites, antioxidants or metabolites involved in phospholipid metabolism have been reported in the early stages, neurometabolic changes during the later post‐natal period are less well characterized. Therefore, we aimed to assess the neurometabolic changes in male Wistar rats between post‐natal days 29 and 77 (p29‐p77) using longitudinal magnetic resonance spectroscopy (MRS) in vivo at 9.4 Tesla. 1H MRS was performed in the hippocampus between p29 and p77 at 1‐week intervals (n = 7) and in the cerebellum between p35 and p77 at 2‐week intervals (n = 7) using the SPECIAL sequence at ultra‐short echo‐time. NOE enhanced and 1H decoupled 31P MR spectra were acquired at p35, p48 and p63 (n = 7) in a larger voxel covering cortex, hippocampus and part of the striatum. The hippocampus showed a decrease in taurine concentration and an increase in glutamate (with more pronounced changes until p49), seemingly a continuation of their well‐described changes in the early post‐natal period. A constant increase in myo‐inositol and choline‐containing compounds in the hippocampus (in particular glycero‐phosphocholine as shown by 31P MRS) was measured throughout the observation period, probably related to membrane metabolism and myelination. The cerebellum showed only a significant increase in myo‐inositol between p35 and p77. In conclusion, this study showed important changes in brain metabolites in both the hippocampus and cerebellum in the later post‐natal period (p29/p35‐p77) of male rats, something previously unreported. Based on these novel data, changes in some neurometabolites beyond p28‐35, conventionally accepted as the cut off for adulthood, should be taken into account in both experimental design and data interpretation in this animal model. [ABSTRACT FROM AUTHOR]

Hippocampus plays a critical role in linking brain energetics and behavior typically associated to stress exposure. In this study, we aimed to simultaneously assess excitatory and inhibitory neuronal metabolism in mouse hippocampus in vivo by applying 18FDG-PET and indirect 13C magnetic resonance spectroscopy (1H-[13C]-MRS) at 14.1 T upon infusion of uniformly 13C-labeled glucose ([U-13C6]Glc). Improving the spectral fitting by taking into account variable decoupling efficiencies of [U-13C6]Glc and refining the compartmentalized model by including two γ-aminobutyric acid (GABA) pools permit us to evaluate the relative contributions of glutamatergic and GABAergic metabolism to total hippocampal neuroenergetics. We report that GABAergic activity accounts for ∼13% of total neurotransmission (VNT) and ∼27% of total neuronal TCA cycle (VTCA) in mouse hippocampus suggesting a higher VTCA/VNT ratio for inhibitory neurons compared to excitatory neurons. Finally, our results provide new strategies and tools for bringing forward the developments and applications of 13C-MRS in specific brain regions of small animals. [ABSTRACT FROM AUTHOR]

d‐amino acid oxidase (DAO) is a peroxisomal enzyme that catalyzes the oxidative deamination of several neutral and basic d‐amino acids to their corresponding α‐keto acids. In most mammalian species studied, high DAO activity is found in the kidney, liver, brain and polymorphonuclear leukocytes, and its main function is to maintain low circulating d‐amino acid levels. DAO expression and activity have been associated with acute and chronic kidney diseases and with several pathologies related to N‐methyl‐d‐aspartate (NMDA) receptor hypo/hyper‐function; however, its precise role is not completely understood. In the present study we show that DAO activity can be detected in vivo in the rat kidney using hyperpolarized d‐[1‐13C]alanine. Following a bolus of hyperpolarized d‐alanine, accumulation of pyruvate, lactate and bicarbonate was observed only when DAO activity was not inhibited. The measured lactate‐to‐d‐alanine ratio was comparable to the values measured when the l‐enantiomer was injected. Metabolites downstream of DAO were not observed when scanning the liver and brain. The conversion of hyperpolarized d‐[1‐13C]alanine to lactate and pyruvate was detected in blood ex vivo, and lactate and bicarbonate were detected on scanning the blood pool in the heart in vivo; however, the bicarbonate‐to‐d‐alanine ratio was significantly lower compared with the kidney. These results demonstrate that the specific metabolism of the two enantiomers of hyperpolarized [1‐13C]alanine in the kidney and in the blood can be distinguished, underscoring the potential of d‐[1‐13C]alanine as a probe of d‐amino acid metabolism. [ABSTRACT FROM AUTHOR]