The case of the missing glutamine

Hancu, Ileana; Port, John D.

doi:10.1002/nbm.1620

Cited by 33 publications

(41 citation statements)

References 34 publications

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“…If one could find a reliable measure of glutamine, in theory one would know the vesicular glutamate levels. Early studies are under way to discover and refine such techniques (72), and two studies of the medial prefrontal cortex of schizophrenic patients (73,74) found evidence of increased glutamine levels, supporting the current model.…”

Section: Future Directionssupporting

confidence: 59%

MR spectroscopy in schizophrenia

Port

Agarwal

2011

Magnetic Resonance Imaging

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The purpose of this study is to review the MR spectroscopic literature regarding schizophrenia. However, as there are over 250 primary MRS articles and dozens of MRS review articles on the subject already, this study will take a different approach. First, the clinical features of schizophrenia will be described. The background neuroanatomy and biochemistry relevant to schizophrenia will be reviewed, as many readers of this journal are unlikely to be familiar with these fields. A current model of the abnormal neural circuitry in schizophrenia will be presented, and predictions extrapolated about relevant metabolite changes over time. Finally, the existing MRS literature will be reviewed in the context of our existing anatomical and chemical knowledge, and future MRS research directions will be elaborated. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.

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Section: Future Directionssupporting

confidence: 59%

MR spectroscopy in schizophrenia

Port

Agarwal

2011

Magnetic Resonance Imaging

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“…This indicates our results may also be applicable to the design of SVS studies. Hancu and Port et al 39 suggest a TE = 80 ms is optimal for Gln with in vivo COVs of 12.7% compared with 122% for a TE = 35 ms. Due to dephasing a shorter TE was better for Glu with simulation COVs of 4.2% for TE = 35 ms and 5.1% for TE = 80 ms. This finding is in agreement with our study.…”

Section: Discussionmentioning

confidence: 99%

Influence of macromolecule baseline on ¹H MR spectroscopic imaging reproducibility

Birch

Peet

Dehghani³

et al. 2016

Magnetic Resonance in Med

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PurposePoorly characterized macromolecular (MM) and baseline artefacts are known to reduce metabolite quantitation accuracy in 1H MR spectroscopic imaging (MRSI). Increasing echo time (TE) and improvements in MM analysis schemes have both been proposed as strategies to improve metabolite measurement reliability. In this study, the influence of TE and two MM analysis schemes on MRSI reproducibility are investigated.MethodsAn experimentally acquired baseline was collected using an inversion recovery sequence (TI = 750 ms) and incorporated into the analysis method. Intrasubject reproducibility of MRSI scans, acquired at 3 Tesla, was assessed using metabolite coefficients of variance (COVs) for both experimentally acquired and simulated MM analysis schemes. In addition, the reproducibility of TE = 35 ms, 80 ms, and 144 ms was evaluated.ResultsTE = 80 ms was the most reproducible for singlet metabolites with COVs < 6% for total N‐acetyl‐aspartate, total creatine, and total choline; however, moderate multiplet dephasing was observed. Analysis incorporating the experimental baseline achieved higher Glu and Glx reproducibility at TE = 35 ms, and showed improvements over the simulated baseline, with higher efficacy for poorer data.ConclusionOverall, TE = 80 ms yielded the most reproducible singlet metabolite estimates. However, combined use of a short TE sequence and the experimental baseline may be preferred as a compromise between accuracy, multiplet dephasing, and T2 bias on metabolite estimates. Magn Reson Med 77:34–43, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

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“…V ex can be in exchange with a 1 H MR invisible but 13 C labeled glutamine pool (Hancu and Port, 2011) or with unlabeled amino acids from the blood (i.e., glutamine), as astrocytes envelop capillaries (Oz et al, 2004). This second glutamine pool could be associated with biosynthetic pathways, which have rates much slower than mitochondrial energy metabolism (McKenna, 2007).…”

Section: Dynamic 13c Magnetic Resonance Spectroscopy (13c Mrs)mentioning

confidence: 99%

How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

2017

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Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS), several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e., indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of 13C isotopomers), the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here, we review state-of-the-art MR methods to study brain function and metabolism in vivo, and their contribution to the current understanding of how astrocytic energy metabolism supports glutamatergic activity and cerebral function. In this context, recent data suggests that astrocytic metabolism has been underestimated. Namely, the rate of oxidative metabolism in astrocytes is about half of that in neurons, and it can increase as much as the rate of neuronal metabolism in response to sensory stimulation.

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The case of the missing glutamine

Cited by 33 publications

References 34 publications

MR spectroscopy in schizophrenia

MR spectroscopy in schizophrenia

Influence of macromolecule baseline on ¹H MR spectroscopic imaging reproducibility

How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

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The case of the missing glutamine

Cited by 33 publications

References 34 publications

MR spectroscopy in schizophrenia

MR spectroscopy in schizophrenia

Influence of macromolecule baseline on 1H MR spectroscopic imaging reproducibility

How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

Contact Info

Product

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Influence of macromolecule baseline on ¹H MR spectroscopic imaging reproducibility