Characterization of Brain Metabolism by Nuclear Magnetic Resonance

Abstract

The noninvasive, quantitative ability of nuclear magnetic resonance (NMR) spectroscopy to characterize small molecule metabolites has long been recognized as a major strength of its application in biology. Numerous techniques exist for characterizing metabolism in living, excised, or extracted tissue, with a particular focus on 1H‐based methods due to the high sensitivity and natural abundance of protons. With the increasing use of high magnetic fields, the utility of in vivo 1H magnetic resonance spectroscopy (MRS) has markedly improved for measuring specific metabolite concentrations in biological tissues. Higher fields, coupled with recent developments in hyperpolarization, also enable techniques for complimenting 1H measurements with spectroscopy of other nuclei, such as 31P and 13C, and for combining measurements of metabolite pools with metabolic flux measurements. We compare ex vivo and in vivo methods for studying metabolism in the brain using NMR and highlight insights gained through using higher magnetic fields, the advent of dissolution dynamic nuclear polarization, and combining in vivo MRS and ex vivo NMR approaches.

Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans

“…Phospholipids are directly implicated in these processes as they provide major structural integrity to the neuropil and myelin. 31 P-MRS can detect key metabolites of cell membrane phospholipid synthesis [phosphomonoesters (PME): phosphocholine (PC) and phosphoethanolamine (PE)], of membrane phospholipid membrane breakdown (phosphodiesters (PDE): glycerophosphocholine (GPC) and glycerophos-phosphoethanolamine (GPE), and turnover (PME/PDE) Downes et al, 2019;Haszto et al, 2020). Hence their quantification provides a measure of membrane expansion and contraction.…”

“…Recently, quantitative and non-invasive measurement of NAD + and NADH in human brain was demonstrated using 31-phosphorus magnetic resonance spectroscopy ( 31 P-MRS) at high magnetic field (Zhu et al, 2015). This technique provides a unique non-invasive tool to monitor NAD level and NAD + /NADH redox ratio changes in humans under healthy and pathological conditions Downes et al, 2019).…”

“…Aside from NAD + and NADH, 31 P-MRS can simultaneously measure other phospho-metabolites involved in energy and membrane phospholipid metabolism Downes et al, 2019), allowing the investigation of their association with the NAD status. This should provide critical mechanistic information such as how the impact of NAD redox dysregulation in aging and neurological diseases affects the brain levels of ATP and phosphocreatine (PCr).…”

High-Resolution Magic Angle Spinning (HR-MAS) NMR-Based Fingerprints Determination in the Medicinal Plant Berberis laurina

“…Nuclear magnetic resonance (NMR) is worldwide well-stablished spectroscopic technique that allows to obtain information related to the genotype, phenotype, and intra- and interorganism classifications based on its origin and biological importance, environmental toxicity, and pollution [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. In such, NMR spectroscopy is widely used in multidisciplinary “omics”, such as metabolomics, metabolic profiling, fingerprinting, and phenotyping [ 11 , 12 , 13 , 14 ], as well as in identification and structural determination of organic compounds in various samples such as food [ 4 ], ice [ 8 ], serum [ 10 ], environmental [ 15 ], material science [ 16 ], and water [ 17 ].…”

Short echo time relaxation‐enhanced MR spectroscopy reveals broad downfield resonances

“…Typically, the short excitation pulse will be immediately followed by acquisition, furnishing ISIS with very short TE capabilities and making it particularly useful for acquiring signals arising from short T 2 spins, such as e.g., 31 P. [15][16][17][18][19] The vast majority of MRS studies explored the spectral region upfield of water, which contains, among others, nonoxygenated aliphatic protons, aliphatic/aromatic acetoxyl protons, as well as methoxy protons. 20 However, the spectrum downfield of the water signal is very rarely investigated by MRS, even though it contains highly relevant chemical functional groups, such as hydroxyls, amines, amides, aldehydes, aromatic, and carboxylic protons, among others. 21 Because some of these biologically-relevant functional groups are present at relatively high concentration in vivo, they could provide complementary information to upfield spectra.…”