Dataset Information

Detection of Glutamate Alterations in the Human Brain Using ¹H-MRS: Comparison of STEAM and sLASER at 7 T.

ABSTRACT:

Purpose

To assess reproducibility of glutamate measurement in the human brain by two short echo time (TE) ¹H-MRS sequences [stimulated echo acquisition mode (STEAM) and semi-localized by adiabatic selective refocusing (sLASER)] at 7 T. Reliable assessment of glutamate is important when studying a variety of neurological and neuropsychiatric disorders. At 7 T, the glutamate signal can be separated from the glutamine signal and hence more accurately measured as compared to lower field strengths. A sLASER sequence has been developed for 7 T, using field focusing at short TE, resulting in twice as much signal as can be obtained using STEAM and improved localization accuracy due to a decreased chemical shift artifact.

Materials and methods

Eight subjects were scanned twice using both STEAM and sLASER. Data were acquired from the frontal and occipital brain region. Subsequently, intraclass correlations were computed for the estimated metabolite concentrations.

Results

sLASER has higher ICC's for glutamate concentration as compared to STEAM in both the frontal and occipital VOI, which is probably due to the higher sensitivity and localization accuracy.

Conclusion

We conclude that sLASER ¹H-MRS at 7 T is a reliable method to obtain reproducible measures of glutamate levels in the human brain at such high accuracy that individual variability, even between age-matched subjects, is measured.

SUBMITTER: Marsman A

PROVIDER: S-EPMC5399075 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Detection of Glutamate Alterations in the Human Brain Using <sup>1</sup>H-MRS: Comparison of STEAM and sLASER at 7 T.

Marsman Anouk A Boer Vincent O VO Luijten Peter R PR Hulshoff Pol Hilleke E HE Klomp Dennis W J DWJ Mandl René C W RCW

Frontiers in psychiatry 20170421

<h4>Purpose</h4>To assess reproducibility of glutamate measurement in the human brain by two short echo time (TE) <sup>1</sup>H-MRS sequences [stimulated echo acquisition mode (STEAM) and semi-localized by adiabatic selective refocusing (sLASER)] at 7 T. Reliable assessment of glutamate is important when studying a variety of neurological and neuropsychiatric disorders. At 7 T, the glutamate signal can be separated from the glutamine signal and hence more accurately measured as compared to lower ...[more]

PMID: 28484398

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Project description:Dysregulation of hippocampus glutamatergic neurotransmission and reductions in hippocampal volume have been associated with psychiatric disorders. The endocannabinoid system modulates glutamate neurotransmission and brain development, including hippocampal remodeling. In humans, elevated levels of anandamide and lower activity of its catabolic enzyme fatty acid amide hydrolase (FAAH) are associated with schizophrenia diagnosis and psychotic symptom severity, respectively (Neuropsychopharmacol, 29(11), 2108-2114; Biol. Psychiatry 88 (9), 727-735). Although preclinical studies provide strong evidence linking anandamide and FAAH to hippocampus neurotransmission and structure, these relationships remain poorly understood in humans. We recruited young adults with and without psychotic disorders and measured FAAH activity, hippocampal glutamate and glutamine (Glx), and hippocampal volume using [11C]CURB positron emission tomography (PET), proton magnetic resonance spectroscopy (1H-MRS) and T1-weighted structural MRI, respectively. We hypothesized that higher FAAH activity would be associated with greater hippocampus Glx and lower hippocampus volume, and that these effects would differ in patients with psychotic disorders relative to healthy control participants. After attrition and quality control, a total of 37 participants (62% male) completed [11C]CURB PET and 1H-MRS of the left hippocampus, and 45 (69% male) completed [11C]CURB PET and hippocampal volumetry. Higher FAAH activity was associated with greater concentration of hippocampal Glx (F1,36.36 = 9.17, p = 0.0045; Cohen's f = 0.30, medium effect size) and smaller hippocampal volume (F1,44.70 = 5.94, p = 0.019, Cohen's f = 0.26, medium effect size). These effects did not differ between psychosis and healthy control groups (no group interaction). This multimodal imaging study provides the first in vivo evidence linking hippocampal Glx and hippocampus volume with endocannabinoid metabolism in the human brain.

Project description:Proton magnetic resonance spectroscopy (1H-MRS) studies have examined glutamatergic abnormalities in schizophrenia and bipolar-I disorders, mostly in single voxels. Though the critical nodes remain unknown, schizophrenia and bipolar-I involve brain networks with broad abnormalities. To provide insight on the biochemical differences that may underlie these networks, the combined glutamine and glutamate signal (Glx) and other metabolites were examined in patients in early psychosis with whole brain 1H-MRS imaging (1H-MRSI). Data were acquired in young schizophrenia subjects (N = 48), bipolar-I subjects (N = 21) and healthy controls (N = 51). Group contrasts for Glx, as well as for N-acetyl aspartate, choline, myo-inositol and creatine, from all voxels that met spectral quality criteria were analyzed in standardized brain space, followed by cluster-corrected level alpha-value (CCLAV ≤ 0.05) analysis. Schizophrenia subjects had higher Glx in the right middle cingulate gyrus (19 voxels, CCLAV = 0.05) than bipolar-I subjects. Healthy controls had intermediate Glx values, though not significant. Schizophrenia subjects also had higher N-acetyl aspartate (three clusters, left occipital, left frontal, right frontal), choline (two clusters, left and right frontal) and myo-inositol (one cluster, left frontal) than bipolar-I, with healthy controls having intermediate values. These increases were likely accounted for by antipsychotic medication effects in the schizophrenia subgroup for N-acetyl aspartate and choline. Likewise, creatine was increased in two clusters in treated vs. antipsychotic-naïve schizophrenia, supporting a medication effect. Conversely, the increments in Glx in right cingulate were not driven by antipsychotic medication exposure. We conclude that increments in Glx in the cingulate may be critical to the pathophysiology of schizophrenia and are consistent with the NMDA hypo-function model. This model however may be more specific to schizophrenia than to psychosis in general. Postmortem and neuromodulation schizophrenia studies focusing on right cingulate, may provide critical mechanistic and therapeutic advancements, respectively.

Dataset Information

Detection of Glutamate Alterations in the Human Brain Using ¹H-MRS: Comparison of STEAM and sLASER at 7 T.

Purpose

Materials and methods

Results

Conclusion

Publications

Detection of Glutamate Alterations in the Human Brain Using <sup>1</sup>H-MRS: Comparison of STEAM and sLASER at 7 T.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Detection of Glutamate Alterations in the Human Brain Using 1H-MRS: Comparison of STEAM and sLASER at 7 T.

Purpose

Materials and methods

Results

Conclusion

Publications

Detection of Glutamate Alterations in the Human Brain Using <sup>1</sup>H-MRS: Comparison of STEAM and sLASER at 7 T.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Detection of Glutamate Alterations in the Human Brain Using ¹H-MRS: Comparison of STEAM and sLASER at 7 T.