Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum

Roalf, David R.; Nanga, Ravi Prakash Reddy; Rupert, Petra; Hariharan, Hari; Quarmley, Megan; Calkins, Monica E.; Dress, Erich; Prabhakaran, Karthik; Elliott, Mark A.; Moberg, Paul J.; Gur, Ruben C.; Gur, Raquel E.; Reddy, Ravinder; Turetsky, Bruce I.

doi:10.1038/mp.2016.258

Cited by 80 publications

(76 citation statements)

References 77 publications

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“…The GluCEST technique has been used in studying the seizure foci in temporal lobe epileptic patients, and showed increased GluCEST contrast on the ipsilateral hippocampus compared with the contralateral hippocampus . In addition, the GluCEST was shown to be a potential biomarker for patients on the psychosis spectrum . In these studies, the GluCEST saturation pulse parameters used were slightly different than those used in the current study.…”

Section: Discussionmentioning

confidence: 90%

“…30 This technique has also been demonstrated in a proof-ofprinciple study in human brain 23 and was recently used in small studies to show differences in brain glutamate levels between patients compared with healthy controls. 25,31 The GluCEST tool is promising for assessing brain glutamate. However, before GluCEST can be implemented in larger clinical studies, the reproducibility of the measurement in healthy subjects must be established.…”

Section: Introductionmentioning

confidence: 99%

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Reproducibility of 2DGluCEST in healthy human volunteers at 7 T

Nanga

DeBrosse

Kumar

et al. 2018

Magnetic Resonance in Med

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PurposeTo investigate the reproducibility of gray and white matter glutamate contrast of a brain slice among a small group of healthy volunteers by using the 2D single‐slice glutamate CEST (GluCEST) imaging technique.MethodsSix healthy volunteers were scanned multiple times for within‐day and between‐day reproducibility. One more volunteer was scanned for within‐day reproducibility at 7T MRI. Glutamate CEST contrast measurements were calculated for within subjects and among the subjects and the coefficient of variations are reported.ResultsThe GluCEST measurements were highly reproducible in the gray and white matter area of the brain slice, whether it was within‐day or between‐day with a coefficient of variation of less than 5%.ConclusionThis preliminary study in a small group of healthy volunteers shows a high degree of reproducibility of GluCEST MRI in brain and holds promise for implementation in studying age‐dependent changes in the brain.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Reproducibility of 2DGluCEST in healthy human volunteers at 7 T

Nanga

DeBrosse

Kumar

et al. 2018

Magnetic Resonance in Med

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“…Recently, CEST imaging of fast‐exchanging amines has also been reported. This CEST effect is centered at around 3 ppm from the water resonance which may originate from glutamate amine and protein lysine amine protons, and which has potential applications in neurological diseases, including Alzheimer's disease, Huntington's disease, epilepsy, psychosis spectrum and dopamine deficiency …”

Section: Introductionmentioning

confidence: 99%

Increased CEST specificity for amide and fast‐exchanging amine protons using exchange‐dependent relaxation rate

Zhang

Wang

et al. 2017

NMR in Biomedicine

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Chemical exchange saturation transfer (CEST) imaging of amides at 3.5 ppm and fast-exchanging amines at 3 ppm provides a unique means to enhance the sensitivity of detection of, for example, proteins/peptides and neurotransmitters, respectively, and hence can provide important information on molecular composition. However, despite the high sensitivity relative to conventional magnetic resonance spectroscopy (MRS), in practice, CEST often has relatively poor specificity. For example, CEST signals are typically influenced by several confounding effects, including direct water saturation (DS), semi-solid non-specific magnetization transfer (MT), the influence of water relaxation times (T ) and nearby overlapping CEST signals. Although several editing techniques have been developed to increase the specificity by removing DS, semi-solid MT and T influences, it is still challenging to remove overlapping CEST signals from different exchanging sites. For instance, the amide proton transfer (APT) signal could be contaminated by CEST effects from fast-exchanging amines at 3 ppm and intermediate-exchanging amines at 2 ppm. The current work applies an exchange-dependent relaxation rate (R ) to address this problem. Simulations demonstrate that: (1) slowly exchanging amides and fast-exchanging amines have distinct dependences on irradiation powers; and (2) R serves as a resonance frequency high-pass filter to selectively reduce CEST signals with resonance frequencies closer to water. These characteristics of R provide a means to isolate the APT signal from amines. In addition, previous studies have shown that CEST signals from fast-exchanging amines have no distinct features around their resonance frequencies. However, R gives Lorentzian lineshapes centered at their resonance frequencies for fast-exchanging amines and thus can significantly increase the specificity of CEST imaging for amides and fast-exchanging amines.

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“…To date, a number of methods based on CEST imaging have been proposed for detecting specific metabolic signals such as glutamate, amide proton, creatine, myo‐inositol, and glycogen . Among them, glutamate CEST (GluCEST), which is sensitive in detecting changes in glutamate concentration resonating at 3.0 ppm from water (0 ppm), has been widely used in brain studies of psychiatric disorders with good quantitative and qualitative results …”

mentioning

confidence: 99%

“…[14][15][16][17][18] Among them, glutamate CEST (GluCEST), which is sensitive in detecting changes in glutamate concentration resonating at 3.0 ppm from water (0 ppm), has been widely used in brain studies of psychiatric disorders with good quantitative and qualitative results. [19][20][21][22] In the present study we aimed to evaluate how stressinduced sleep disturbance in a rat model changes glutamate levels by applying the well-validated GluCEST imaging technique. Moreover, we carried out 1 H MRS on the same model to measure glutamate concentrations and assessed the correlation between 1 H MRS and GluCEST signals.…”

mentioning

confidence: 99%

Cerebral mapping of glutamate using chemical exchange saturation transfer imaging in a rat model of stress‐induced sleep disturbance at 7.0T

Lee

Woo

Kwon

et al. 2019

Magnetic Resonance Imaging

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Background Glutamate chemical exchange saturation transfer (GluCEST) imaging has been widely used in brain psychiatric disorders. Glutamate signal changes may help to evaluate the sleep‐related disorders, and could be useful in diagnosis. Purpose To evaluate signal changes in the hippocampus and cortex of a rat model of stress‐induced sleep disturbance using GluCEST. Study Type Prospective animal study. Animal Model Fourteen male Sprague–Dawley rats. Field Strength/Sequence 7.0T small bore MRI / fat‐suppressed, turbo‐rapid acquisition with relaxation enhancement (RARE) for CEST, and spin‐echo, point‐resolved proton MR spectroscopy (1H MRS). Assessment Rats were divided into two groups: the stress‐induced sleep‐disturbance group (SSD, n = 7) and the control group (CTRL, n = 7), to evaluate and compare the cerebral glutamate signal changes. GluCEST data were quantified using a conventional magnetization transfer ratio asymmetry in the left‐ and right‐side hippocampus and cortex. The correlation between GluCEST signal and glutamate concentrations, derived from 1H MRS, was evaluated. Statistical Analysis Wilcoxon rank‐sum test between CEST signals and multiparametric MR signals, Wilcoxon signed‐rank test between CEST signals on the left and right hemispheres, and a correlation test between CEST signals and glutamate concentrations derived from 1H MRS. Results Measured GluCEST signals showed significant differences between the two groups (left hippocampus; 4.23 ± 0.27% / 5.27 ± 0.42% [SSD / CTRL, P = 0.002], right hippocampus; 4.50 ± 0.44% / 5.04 ± 0.34% [P = 0.035], left cortex; 2.81 ± 0.38% / 3.56 ± 0.41% [P = 0.004], and right cortex; 2.95 ± 0.47% / 3.82 ± 0.26% [P = 0.003]). GluCEST signals showed positive correlation with glutamate concentrations (R2 = 0.312; P = 0.038). Data Conclusion GluCEST allowed the visualization of cerebral glutamate changes in rats subjected to sleep disturbance, and may yield valuable insights for interpreting alterations in cerebral biochemical information. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1866–1872.

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Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum

Cited by 80 publications

References 77 publications

Reproducibility of 2DGluCEST in healthy human volunteers at 7 T

Reproducibility of 2DGluCEST in healthy human volunteers at 7 T

Increased CEST specificity for amide and fast‐exchanging amine protons using exchange‐dependent relaxation rate

Cerebral mapping of glutamate using chemical exchange saturation transfer imaging in a rat model of stress‐induced sleep disturbance at 7.0T

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