Abstract
Purpose: To investigate glutamate signal distributions in multiple brain regions of a healthy rat brain using glutamate-weighted chemical exchange saturation transfer (GluCEST) imaging. Method: The GluCEST data were obtained using a 7.0 T magnetic resonance imaging (MRI) scanner, and all data were analyzed using conventional magnetization transfer ratio asymmetry in eight brain regions (cortex, hippocampus, corpus callosum, and rest of midbrain in each hemisphere). GluCEST data acquisition was performed again one month later in five randomly selected rats to evaluate the stability of the GluCEST signal. To evaluate glutamate level changes calculated by GluCEST data, we compared the results with the concentration of glutamate acquired from 1H magnetic resonance spectroscopy (1H MRS) data in the cortex and hippocampus. Results: GluCEST signals showed significant differences (all p ≤ 0.001) between the corpus callosum (−1.71 ± 1.04%; white matter) and other brain regions (3.59 ± 0.41%, cortex; 5.47 ± 0.61%, hippocampus; 4.49 ± 1.11%, rest of midbrain; gray matter). The stability test of GluCEST findings for each brain region was not significantly different (all p ≥ 0.263). In line with the GluCEST results, glutamate concentrations measured by 1H MRS also appeared higher in the hippocampus (7.30 ± 0.16 μmol/g) than the cortex (6.89 ± 0.72 μmol/g). Conclusion: Mapping of GluCEST signals in the healthy rat brain clearly visualize glutamate distributions. These findings may yield a valuable database and insights for comparing glutamate signal changes in pre-clinical brain diseases.
Highlights
Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system and is involved in neuronal function [1,2,3]
Glutamatergic dysfunction in the brain is implicated in various neuropsychiatric disorders such as epilepsy, Alzheimer’s disease, autism, and aging, as well as neurological issues stemming from gross abnormalities such as ischemia or tumors [4,5,6,7,8,9]
The visible upward shifts in the Z-spectra in the gray matter regions are due to the narrowing of the direct water saturation (DS) curve caused by the difference in relaxation time (T2 )
Summary
Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system and is involved in neuronal function [1,2,3]. Detecting in vivo glutamate signal changes in the brain can be applied to the diagnosis and treatment plan of multiple diseases where glutamate changes are involved and may play a role as a biomarker for neurological diseases in vivo. A variety of studies using medical imaging modalities such as magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), single-photon emission tomography (SPECT), and positron emission tomography (PET) have attempted to image the distribution of in vivo neurotransmitters, glutamate, in the brain [10,11,12,13,14,15]. MR-based imaging and quantification methods have high enough resolution to provide details of brain structure with MRI and to show neurological changes by MRS. MRS has sufficient sensitivity to detect neurotransmitters in many areas of the brain, direct quantification of neurotransmitters in certain cases, such as separation of individual pools of glutamate, is limited in clinical MRI systems (≤3 T). The use of MRS with an ultra-high field (≥7 T) provides improved sensitivity because of high Larmor frequency and improved chemical shift dispersion, allowing better characterization of individual responses. [16]
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