scholarly journals Cerebral Glutamine Metabolism under Hyperammonemia Determined in vivo by Localized 1H and 15N NMR Spectroscopy

2011 ◽  
Vol 32 (4) ◽  
pp. 696-708 ◽  
Author(s):  
Cristina Cudalbu ◽  
Bernard Lanz ◽  
João MN Duarte ◽  
Florence D Morgenthaler ◽  
Yves Pilloud ◽  
...  
Keyword(s):  
Pulse Sequence ◽  
Glutamine Metabolism ◽  
15N Nmr ◽  
Resonance Spectroscopy ◽  
Reliable Determination ◽  
Noninvasive Measurements ◽  
15N Nmr Spectroscopy ◽  
First Time ◽  
Cerebral Glutamine

Brain glutamine synthetase (GS) is an integral part of the glutamate—glutamine cycle and occurs in the glial compartment. In vivo Magnetic Resonance Spectroscopy (MRS) allows noninvasive measurements of the concentrations and synthesis rates of metabolites. 15N MRS is an alternative approach to 13C MRS. Incorporation of labeled 15N from ammonia in cerebral glutamine allows to measure several metabolic reactions related to nitrogen metabolism, including the glutamate—glutamine cycle. To measure 15N incorporation into the position 5N of glutamine and position 2N of glutamate and glutamine, we developed a novel 15N pulse sequence to simultaneously detect, for the first time, [5-15N]Gln and [2-15N]Gln + Glu in vivo in the rat brain. In addition, we also measured for the first time in the same experiment localized 1H spectra for a direct measurement of the net glutamine accumulation. Mathematical modeling of 1H and 15N MRS data allowed to reduce the number of assumptions and provided reliable determination of GS (0.30 ± 0.050 μmol/g per minute), apparent neurotransmission (0.26 ± 0.030 μmol/g per minute), glutamate dehydrogenase (0.029 ± 0.002 μmol/g per minute), and net glutamine accumulation (0.033 ± 0.001 μmol/g per minute). These results showed an increase of GS and net glutamine accumulation under hyperammonemia, supporting the concept of their implication in cerebral ammonia detoxification.

scholarly journals In vivo 13C MRS in the mouse brain at 14.1 Tesla and metabolic flux quantification under infusion of [1,6-13C2]glucose

2017 ◽  
Vol 38 (10) ◽  
pp. 1701-1714 ◽  
Author(s):  
Marta Lai ◽  
Bernard Lanz ◽  
Carole Poitry-Yamate ◽  
Jackeline F Romero ◽  
Corina M Berset ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Metabolic Flux ◽  
Direct Detection ◽  
Tricarboxylic Acid Cycle ◽  
Quantitative Information ◽  
Glutamine Metabolism ◽  
Resonance Spectroscopy ◽  
Flux Analysis ◽  
Carboxylase Activity

In vivo 13C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing 13C-labeled glucose. Metabolic flux analysis of 13C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, 13C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6-13C2]glucose for up to 5 h. 13C incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were detected dynamically and fitted to a two-compartment model: flux estimation of neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in astrocytes (Vg = 0.16 ± 0.03 µmol/g/min) and neurons (VTCAn = 0.56 ± 0.03 µmol/g/min), pyruvate carboxylase activity (VPC = 0.041 ± 0.003 µmol/g/min) and neurotransmission rate (VNT = 0.084 ± 0.008 µmol/g/min), resulting in a cerebral metabolic rate of glucose (CMRglc) of 0.38 ± 0.02 µmol/g/min, in excellent agreement with that determined with concomitant 18F-fluorodeoxyglucose positron emission tomography (18FDG PET).We conclude that modeling of neuron-glial metabolism in vivo is accessible in the mouse brain from 13C direct detection with an unprecedented spatial resolution under [1,6-13C2]glucose infusion.

scholarly journals Noninvasive Measurements of Human Brain Temperature Using Volume-Localized Proton Magnetic Resonance Spectroscopy

1997 ◽  
Vol 17 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Ron Corbett ◽  
Abbot Laptook ◽  
Paul Weatherall
Keyword(s):  
Magnetic Resonance ◽  
Frontal Lobe ◽  
Mr Spectroscopy ◽  
Brain Temperature ◽  
Human Subjects ◽  
Normal Subjects ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Noninvasive Measurements

Elucidation of the role of cerebral hyperthermia as a secondary factor that worsens outcome after brain injury, and the therapeutic application of modest brain hypothermia would benefit from noninvasive measurements of absolute brain temperature. The present study was performed to evaluate the feasibility of using 1H magnetic resonance (MR) spectroscopy to measure absolute brain temperature in human subjects on a clinical imaging spectroscopy system operating at a field strength of 1.5 T. In vivo calibration results were obtained from swine brain during whole-body heating and cooling, with concurrent measurements of brain temperature via implanted probes. Plots of the frequency differences between the in vivo MR peaks of water and N-acetyl-aspartate and related compounds (NAX), or water and choline and other trimethylamines versus brain temperature were linear over the temperature range studied (28–40°C). These relationships were used to estimate brain temperature from 1H MR spectra obtained from 10 adult human volunteers from 4 cm3-volumes selected from the frontal lobe and thalamus. Oral and forehead temperatures were monitored concurrently with MR data collection to verify normothermia in all the subjects studied. Temperatures determined using N-acetyl-aspartate or choline as the chemical shift reference did not differ significantly, and therefore results from these estimates were averaged. The brain temperature (mean ± SD) measured from the frontal lobe (37.2 = 0.6°C) and thalamus (37.7 ± 0.6°C) were significantly different from each other (paired t-test, p = 0.035). We conclude that 1H MR spectroscopy provides a viable noninvasive means of measuring regional brain temperatures in normal subjects and is a promising approach for measuring temperatures in brain-injured subjects.

Anwendung der 15N-NMR-Spektroskopie zur Charakterisierung reaktiver, koordinativ ungesättigter Zinn-, Bleiund Phosphor-Stickstoff-Verbindungen / Application of 15N-NMR Spectroscopy to the Characterization of Reactive, Coordinatively Unsaturated Tin-, Lead- and Phosphorus-Nitrogen Compounds

1987 ◽  
Vol 42 (12) ◽  
pp. 1515-1519 ◽  
Author(s):  
Carin Stader ◽  
Bernd Wrackmeyer
Keyword(s):  
Nmr Spectra ◽  
Pulse Sequence ◽  
Coupling Constants ◽  
Spin Coupling ◽  
15N Nmr ◽  
Nmr Data ◽  
15N Nmr Spectroscopy ◽  
Spin Coupling Constants ◽  
Spin Spin Coupling

AbstractThe basic INEPT pulse sequence proved most useful for recording 15N NMR spectra at natural abundance of bis(amino)stannvlenes (1). -plumbylenes (2) and of imino-amino-λ2-phosphanes (3), where the nitrogen atoms carry bulky substituents like Me3Si-, t-Bu-, 2.4.4-trimethyl-2- pentyl-groups (t-Oct-groups) or are part of the 2.2.6.6-tetramethylpiperidinyl group. The sensitiv­ity of this technique is proved by the observation of 117/119Sn or 207Pb satellites owing to spin-spin coupling constants 1J(117/119Sn15N) and 1J(117/119Pb15N), respectively. NMR data of bis[bis(trimethylsilyl)methyl]tin (4) are reported in order to corroborate the arguments for the interpretation of the δ(15N) and 1J(119Sn15N) data. The 15N NMR data of the λ2-phosphanes (3) indicate a bonding situation similar to that in triazenes.

scholarly journals Current Practice and New Developments in the Use of In Vivo Magnetic Resonance Spectroscopy for the Assessment of Key Metabolites Implicated in the Pathophysiology of Schizophrenia

2019 ◽  
Vol 18 (21) ◽  
pp. 1908-1924 ◽  
Author(s):  
Gerard E. Dwyer ◽  
Kenneth Hugdahl ◽  
Karsten Specht ◽  
Renate Grüner
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Pulse Sequence ◽  
Resonance Spectroscopy ◽  
New Developments ◽  
Single Voxel ◽  
In Vivo Spectroscopy ◽  
Pulse Sequence Design ◽  
Review Current

Magnetic Resonance Spectroscopy (MRS) has become a valuable tool for investigating the biochemical bases of both normal processes in the healthy brain and elucidating the pathophysiology of neuropsychiatric disorders. As a rapidly advancing field, new developments in pulse sequence design have seen new possibilities arise in terms of what can be done with in vivo spectroscopy. While the applications of MRS are numerous, this review has been confined to the use of single voxel spectroscopy in the assessment of five key metabolites and their roles in schizophrenia: N-acetylaspartate (NAA), glutamate (Glu) and glutamine (Gln), γ-aminobutyric acid (GABA) and glutathione (GSH). This article will briefly cover the roles they play in schizophrenia, review current methods being used in their assessment and highlight new approaches that may potentially overcome some of the limitations current methods pose.

scholarly journals From synaptic activity to human in vivo quantification of neurotransmitter dynamics: a neural modelling approach

2021 ◽  
Author(s):  
Caroline A. Lea-Carnall ◽  
Wael El-Deredy ◽  
Stephen R. Williams ◽  
Charlotte J. Stagg ◽  
Nelson J. Trujillo-Barreto
Keyword(s):  
Mean Field ◽  
Neural Dynamics ◽  
Resonance Spectroscopy ◽  
Mean Field Model ◽  
Physiological Basis ◽  
1H Magnetic Resonance Spectroscopy ◽  
Dependent Change ◽  
First Time ◽  
Activity Dependent

AbstractUnderstanding the role of neurotransmitters glutamate and GABA during normal and abnormal brain function and under external stimulation in humans are critical neuroscientific and clinical goals. The recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neuro-transmitter activity in vivo for the first time. However, the physiological basis of the observed fMRS signal remains unclear. It has been proposed that fMRS detects shifts in metabolite concentrations as they move from presynaptic vesicles, where they are largely invisible, to extracellular and cytosolic pools, where they are visible.Here we bridge the gap between neural dynamics and fMRS by developing a mean-field model to link the neurotransmitter dynamics at the microscopic-level to the macroscopic-level imaging measurements. GABA and glutamate are described as cycling between three metabolic pools: in the vesicles; active in the cleft; or undergoing recycling in the astrocytic or neuronal cytosol. We interrogate the model by applying a current to manipulate the mean membrane potential and firing rate of the neural populations.We find that by disregarding the contribution from the vesicular pool, our model predicts activity-dependent changes in the MRS signal, which are consistent with reported empirical findings. Further, we show that current magnitude and direction has a selective effect on the GABA/glutamate-MRS signal: inhibitory stimulation leads to reduction of both metabolites, whereas excitatory stimulation leads to increased glutamate and decreased GABA. In doing so, we link neural dynamics and fMRS and provide a mechanistic account for the activity-dependent change in the observed MRS signal.Key Points SummaryThe recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neurotransmitter activity in vivo for the first time in humans. However, the physiological basis of the observed fMRS signal is unclear.It has been proposed that fMRS detects shifts in metabolite concentrations as they move from presynaptic vesicles, where they are largely invisible to MRS, to extracellular and cytosolic pools, where they are visible to MRS.We test this hypothesis using a mean field model which links the neural dynamics of neurotransmitters at the microscopic-level to the macroscopic-level imaging measurements obtained in experimental studies.By disregarding activity in the vesicular pool, our model can generate activity-dependent changes in the MRS signal in response to stimulation which are consistent with experimental findings in the literature.We provide a mechanistic account for the activity-dependent change in observed neurotransmitter concentrations using MRS.

scholarly journals Effect of Deep Pentobarbital Anesthesia on Neurotransmitter Metabolism in Vivo: On the Correlation of Total Glucose Consumption with Glutamatergic Action

2002 ◽  
Vol 22 (11) ◽  
pp. 1343-1351 ◽  
Author(s):  
In-Young Choi ◽  
Hongxia Lei ◽  
Rolf Gruetter
Keyword(s):  
Glucose Metabolism ◽  
Tca Cycle ◽  
Reaction Rates ◽  
Glutamine Metabolism ◽  
Resonance Spectroscopy ◽  
Metabolic Reaction ◽  
Glutamatergic Neurotransmission ◽  
Brain Glucose ◽  
Neurotransmitter Metabolism

The effect of deep barbiturate anesthesia on brain glucose transport, TCA cycle flux, and aspartate, glutamate, and glutamine metabolism was assessed in the rat brain in vivo using 13C nuclear magnetic resonance spectroscopy at 9.4 T in conjunction with [1-13C] glucose infusions. Brain glucose concentrations were elevated, consistent with a twofold reduced cerebral metabolic rate for glucose (CMRglc) compared with light α-chloralose anesthesia. Using a mathematical model of neurotransmitter metabolism, several metabolic reaction rates were extracted from the rate of label incorporation. Total oxidative glucose metabolism, CMRglc(ox), was 0.33 ± 0.03 μmol·g−1 · min−1. The neuronal TCA cycle rate was similar to that in the glia, 0.35 ± 0.03 μmol · g−1 · min−1 and 0.26 ± 0.06 μmol · g−1 · min−1, respectively, suggesting that neuronal energy metabolism was mainly affected. The rate of pyruvate carboxylation was 0.03 ± 0.01 μmol·g−1 · min−1. The exchange rate between cytosolic glutamate and mitochondrial 2-oxoglutarate, Vx, was equal to the rate of neuronal pyruvate dehydrogenase flux. This indicates that Vx is coupled to CMRglc(ox), implying that the malate-aspartate shuttle is the major mechanism that facilitates label exchange across the inner mitochondrial membrane. The apparent rate of glutamatergic neurotransmission, VNT, was 0.04 ± 0.01 μmol·g−1 · min−1, consistent with strong reductions in electrical activity. However, the rates of cerebral oxidative glucose metabolism and glutamatergic neurotransmission, CMRglc(ox)/VNT, did not correlate with a 1:1 stoichiometry.

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