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

Abstract

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.

Regional Mapping of Brain Glutamate Distributions Using Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging

“…Nevertheless, as we mentioned earlier, our results demonstrate a clear signal contrast between gray and white matter. Furthermore, a comparison with a previous study on GluCEST imaging in the rat brain at 7 T showed that the quantitative signal levels in the hippocampus (~5.2%) and cortex (~3.5%) are comparable to the results of this study [ 31 ]. It would be prudent in future studies to increase scan points with multiple cross-sectional slices or 3D data acquisition for GluCEST imaging analysis to evaluate signals in the extended brain regions.…”

“…It has been used with multiple proton-exchanging solutes such as glutamate, amides, creatine, and glycogen, and applied in multiple brain studies to monitor in vivo changes in solute concentration and exchange-related properties. [ 19 , 20 , 21 , 22 , 23 ] Imaging of in vivo glutamate using glutamate CEST (GluCEST) has been demonstrated in various in vivo brain studies [ 16 , 22 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. The application of GluCEST not only depicts changes in glutamate associated with brain diseases as described in previous studies [ 22 , 24 , 25 , 26 , 27 , 29 , 31 , 32 ] but also shows the difference between gray matter and white matter in the subcortical area in healthy human subjects [ 16 , 28 ].…”

Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging in Pre-clinical and Clinical Applications for Encephalitis

“… Bagga et al (2016 , 2018) successfully used GluCEST MRI in a mouse model of dopamine deficiency and Parkinson’s disease to measure spatial changes in Glu. Davis et al (2015) showed that GluCEST MRI allows the visualization of cerebral Glu changes in rat models of stress-induced sleep disturbance and status epilepticus ( Lee et al, 2019 ). Crescenzi et al (2014) identified Glu deficits in mouse models of dementia using GluCEST imaging.…”

GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First‐Episode and Early‐Onset Major Depression Disorder

“…GluCEST has typically been performed at 7 T or higher fields in previous studies. 22,23 This study attempted to conduct a preliminary investigation of hippocampal glutamate concentration changes in first-onset MDD using a 3-T GluCEST sequence and the result showed that the GluCEST values of the left hippocampus in MDD patients were lower than those in HCs. The same result of GluCEST reduction in the left hippocampus of chronic unpredictable mild stress (CUMS) rats was confirmed in a previous study.…”

“…Haris et al 26 found that the GluCEST values and Glx/Cr in the right cerebral hemisphere of Alzheimer's disease mice were lower than those in the controls. In addition, Lee et al 23 showed that glutamate concentrations measured by 1 H MRS were significantly decreased in the left hippocampus of the stress-induced sleep-disturbance (SDD) rats compared with the controls, and the GluCEST values in the hippocampus of both hemispheres were significantly decreased in the SSD compared with the controls. These studies showed the same changing trend as we did.…”