In-vivo Magnetic Resonance Imaging of GABA and Glutamate (original) (raw)
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Magnetic Resonance in Medicine, 2013
The effects of radio frequency field (B 1 ) inhomogeneity on measured in vivo human brain glutamate chemical exchange saturation transfer contrast maps are normally confounded with contributions from chemical exchange saturation transfer, direct saturation and magnetization transfer effects. Consequently, the chemical exchange saturation transfer effect variation with B 1 follows a complicated function and depends on the tissue types as well. In this work, we developed and tested a novel approach for B 1 inhomogeneity correction based on acquiring calibration data at a coarsely sampled B 1 values in conjunction with the measured B 1 maps. With this approach, different calibration curves are derived for gray matter and white matter instead of a simple linear scaling based on local B 1 values. Potential extensions of this approach to study chemical exchange saturation transfer contrast from other metabolites and tissue types are discussed. Magn Reson Med 000:000-000, 2012. V C 2012 Wiley Periodicals, Inc.
Localized in vivo 13C-NMR of Glutamate Metabolism in the Human Brain: Initial Results at 4 Tesla
Developmental Neuroscience, 1998
Using optimized administration of 13 C-labeled glucose, the time course of the specific activity of glucose was measured directly by in vivo 13 C-NMR in the human brain at 4 Tesla. Subsequent label incorporation was measured at the C2, C3 and C4 positions of both glutamate and the well-resolved C2, C3 and C4 resonances of glutamine and at the C2 and C3 positions of aspartate. GABA was clearly observed for the first time in vivo, suggesting a substantial GABA turnover in the normal human visual cortex. Likewise, lactate C3 labeled with an estimated active pool size on the order of 0.5 mM. A model of cerebral glutamate metabolism is proposed which predicts that glutamatergic action ('neurotransmission'), pyruvate carboxylase flux, TCA cycle activity, glucose consumption and exchange across the mitochondrial membrane can be assessed simultaneously in the human brain. OOOOOOOOOOOOOOOOOOOOOO
NMR in biomedicine, 2017
γ-Aminobutyric acid (GABA) and glutamate (Glu), major neurotransmitters in the brain, are recycled through glutamine (Gln). All three metabolites can be measured by magnetic resonance spectroscopy in vivo, although GABA measurement at 3 T requires an extra editing acquisition, such as Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS). In a GABA-edited MEGA-PRESS spectrum, Glu and Gln co-edit with GABA, providing the possibility to measure all three in one acquisition. In this study, we investigated the reliability of the composite Glu + Gln (Glx) peak estimation and the possibility of Glu and Gln separation in GABA-edited MEGA-PRESS spectra. The data acquired in vivo were used to develop a quality assessment framework which identified MEGA-PRESS spectra in which Glu and Gln could be estimated reliably. Phantoms containing Glu, Gln, GABA and N-acetylaspartate (NAA) at different concentrations were scanned using GABA-edited MEGA-PRESS at 3 T. Fifty-six sets of spectra in five b...
Mapping glutamate in subcortical brain structures using high-resolution GluCEST MRI
NMR in Biomedicine, 2013
In vivo measurement of glutamate (Glu) in brain subcortex can elucidate the role these structures play in cognition and neuropsychiatric disorders. However, accurate quantification of Glu in subcortical regions is challenging. Recently, a novel MRI method based on the Glu chemical exchange saturation transfer (GluCEST) effect has been developed for detecting brain Glu in millimolar concentrations. Here, we use GluCEST to map Glu distributions in subcortical structures of the human brain (e.g. amygdala, hippocampus). Overall, GluCEST was~40% higher in gray matter than in white matter. Within the subcortical gray matters, amygdala showed the highest GluCEST contrast. Utilizing MR spectroscopic data, in vivo GluCEST detection sensitivity (~0.8% mM À1) in subcortical gray matter was evaluated and was consistent with the previously reported values. In general, the GluCEST map approximates the Glu receptor distribution reported in previous positron emission tomography (PET) studies. These findings suggest that high-resolution GluCEST MRI of subcortical brain structures may prove to be a useful tool in diagnosis of brain disorders or treatment responses.
Magnetic resonance imaging of glutamate
Glutamate (Glu) exhibits a pH and concentration dependent chemical exchange saturation transfer effect (CEST) between its -amine group and bulk water, here termed GluCEST. GluCEST asymmetry is observed at ~3 parts per million downfield from bulk water. Following middle cerebral artery occlusion in the rat brain, an approximately 100% elevation of GluCEST in the ipsilateral side compared to the contralateral side was observed, and is predominantly due to pH changes. In a rat brain tumor model with blood brain barrier disruption, intravenous Glu injection resulted in a clear elevation of GluCEST and a comparable increase in the proton magnetic resonance spectroscopy signal of Glu. GluCEST maps from healthy human brain at 7T were also obtained. These results demonstrate the feasibility and potential of GluCEST for mapping relative changes in Glu concentration as well as pH in vivo. Potential contributions from other brain metabolites to the GluCEST effect are also discussed.
A B S T R A C T Imbalances in glutamatergic (excitatory) and GABA (inhibitory) signalling within key brain networks are thought to underlie many brain and mental health disorders, and for this reason there is considerable interest in investigating how individual variability in localised concentrations of these molecules relate to brain disorders. Magnetic resonance spectroscopy (MRS) provides a reliable means of measuring, in vivo, concentrations of neurometabolites such as GABA, glutamate and glutamine that can be correlated with brain function and dysfunction. However, an issue of much debate is whether the GABA observed and measured using MRS represents the entire pool of GABA available for measurement (i.e., metabolic, intracellular, and extracellular) or is instead limited to only some portion of it. GABA function can also be investigated indirectly in humans through the use of non-invasive transcranial magnetic stimulation (TMS) techniques that can be used to measure cortical excitability and GABA-mediated physiological inhibition. To investigate this issue further we collected in a single session both types of measurement, i.e., TMS measures of cortical excitability and physiological inhibition and ultra-high-field (7 T) MRS measures of GABA, glutamate and glutamine, from the left sensorimotor cortex of the same group of right-handed individuals. We found that TMS and MRS measures were largely uncorrelated with one another, save for the plateau of the TMS IO curve that was negatively correlated with MRS-Glutamate (Glu) and intra-cortical facilitation (10ms ISI) that was positively associated with MRS-Glutamate concentration. These findings are consistent with the view that the GABA concentrations measured using the MRS largely represent pools of GABA that are linked to tonic rather than phasic inhibition and thus contribute to the inhibitory tone of a brain area rather than GABAergic synaptic transmission.
Polish Journal of Radiology, 2019
The work describes the physical basis of the chemical exchange saturation transfer (CEST) technique; it presents the beginnings of the implementation of the method and its possible applications. The principles of correct data acquisition and possible solutions used during the design of the CEST sequence are shown. The main problems related to data analysis are indicated, and an example Z-spectrum from in vivo study of the rat brain is introduced. Furthermore, the parameters related to spectrum analyses such as magnetisation transfer asymmetry (MTRasym) and amide proton transfer asymmetry (APTasym) are presented. In the following part, different types of the CEST method often mentioned in the literature are discussed. Subsequently, the possible applications of the CEST method in both clinical and experimental practice are described.
Imaging in Vivo Glutamate Fluctuations with [11C]ABP688: A GLT-1 Challenge with Ceftriaxone
Journal of Cerebral Blood Flow & Metabolism, 2015
Molecular imaging offers unprecedented opportunities for investigating dynamic changes underlying neuropsychiatric conditions. Here, we evaluated whether [11C]ABP688, a positron emission tomography (PET) ligand that binds to the allosteric site of the metabotropic glutamate receptor type 5 (mGluR5), is sensitive to glutamate fluctuations after a pharmacological challenge. For this, we used ceftriaxone (CEF) administration in rats, an activator of the GLT-1 transporter (EAAT2), which is known to decrease extracellular levels of glutamate. MicroPET [11C]ABP688 dynamic acquisitions were conducted in rats after a venous injection of either saline (baseline) or CEF 200 mg/kg (challenge). Binding potentials (BPND) were obtained using the simplified reference tissue method. Between-condition statistical parametric maps indicating brain regions showing the highest CEF effects guided placement of microdialysis probes for subsequent assessment of extracellular levels of glutamate. The CEF adm...
Journal of Neurochemistry, 2010
The simultaneous quantification of excitatory and inhibitory neurotransmission and the associated energy metabolism is crucial for a proper understanding of brain function. While the detection of glutamatergic neurotransmission in vivo by 13 C NMR spectroscopy is now relatively routine, the detection of GABAergic neurotransmission in vivo has remained elusive due to the low GABA concentration and spectral overlap. Using 1 H-[ 13 C] NMR spectroscopy at high magnetic field in combination with robust spectral modeling and the use of different substrates, [U-13 C 6 ]-glucose and [2-13 C]-acetate, it is shown that GABAergic, as well as glutamatergic neurotransmitter fluxes can be detected non-invasively in rat brain in vivo.