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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 (1 H 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 1 H 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 1 H 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.

Tumor heterogeneity is an important concept when assessing intratumoral variety in vascular phenotypes and responses to antiangiogenic treatment. This study explored spatiotemporal heterogeneity of vascular alterations in C6 glioma mice during tumor growth and antiangiogenic treatment on serial MR examinations (days 0, 4, and 7 from initiation of vehicle or multireceptor tyrosine kinase inhibitor administration). Transvascular permeability (TP) was quantified on dynamic‐contrast‐enhanced MRI (DCE‐MRI) using extravascular extracellular agent (Gd‐DOTA); blood volume (BV) was estimated using intravascular T2 agent (SPION). With regard to region‐dependent variability in vascular phenotypes, the control group demonstrated higher TP in the tumor center than in the periphery, and greater BV in the tumor periphery than in the center. This distribution pattern became more apparent with tumor growth. Antiangiogenic treatment effect was regionally heterogeneous: in the tumor center, treatment significantly suppressed the increase in TP and decrease in BV (ie, typical temporal change in the control group); in the tumor periphery, treatment‐induced vascular alterations were insignificant and BV remained high. On histopathological examination, the control group showed greater CD31, VEGFR2, Ki67, and NG2 expression in the tumor periphery than in the center. After treatment, CD31 and Ki67 expression was significantly suppressed only in the tumor center, whereas VEGFR2 and α‐caspase 3 expression was decreased and NG2 expression was increased in the entire tumor. These results demonstrate that MRI can reliably depict spatial heterogeneity in tumor vascular phenotypes and antiangiogenic treatment effects. Preserved angiogenic activity (high BV on MRI and high CD31) and proliferation (high Ki67) in the tumor periphery after treatment may provide insights into the mechanism of tumor resistance to antiangiogenic treatment.

The purpose of this study is to design a simple image intensity compensation SIMIC method prior to the application of a variety of cost functions for distortion correction in diffusion tensor imaging DTI. The synthetic dataset consists of each direction of diffusion weighted imaging DWI made by multiplication of nondiffusion weighted image b = 0 image and tensor matrices. We added the effects of patient motion and eddy current distortion using translation, rotation, scaling and shearing matrices. We calculated the b = 0 image of each direction from original DTI, inversely. A co-registration method was applied to the extracted b = 0 images of each direction based on the original b = 0 image and then, the transformation matrices were generated and the original DTI were transformed using this transformation matrix. For the DTI distortion correction, two kinds of cost functions, normalized mutual information NMI and normalized cross-correlation NCC, were used. Visual assessments and quantitative measurements were used to evaluate the results. When using the NMI as a cost function, the quantitative results showed no significant differences between NMI and NMI with SIMIC method. However, there are significant differences compared with using the NCC as a cost function. Our study showed cost function for image distortion correction with SIMIC method improved the results both quantitatively and in terms of qualitative accuracy. This method may be helpful for DTI analysis and helpful for increasing accuracy. © 2015 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 25, 328-33, 2015

Subanesthetic doses of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in patients with schizophrenia. In the present study, in vivo 1H-MRS and ex vivo 1H high-resolution magic angle spinning (HR-MAS) spectroscopy was used to examine the brain metabolism of rats treated with subanesthetic doses of ketamine (30 mg/kg) for 6 days. A single voxel localization sequence (PRESS, TR/TE = 4000/20 ms and NEX = 512) was used to acquire the spectra in a 30-µl voxel positioned in the cerebral cortex (including mainly PFC) of the rats (ketamine group: n = 12; saline group: n = 12) anesthetized with isoflurane. After the in vivo 1H-MRS acquisition, the animals were sacrificed and the cerebral cortex tissues were extracted (ketamine group: n = 7; saline group: n = 7) for ex vivo 1H HR-MAS spectroscopy (CPMG sequence, 2.0-s presaturation delay, 2.0-s acquisition time, 128 transients and 4-ms inter-pulse delay) using a 500-MHz NMR spectrometer. All proton metabolites were quantified using the LCModel. For the in vivo spectra, there was a significant increase in glutamate concentration in the cerebral cortex of the ketamine group compared with the controls (p

Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of repeated intermittent ethanol intoxication in the frontal cortex.

Purpose: The objectives of this study were to develop MRI-MRS fused phantom with metabolite inserts for QA, to optimize simultaneously QA parameters using fused phantom and to conduct quantitative analysis of sixteen metabolites solution with layered shape vials using localization sequence. Methods: The circular cylinder body was filled with waterdiluted CuSO4(0.7g/L) for having a T1 time shorting function and NaCl(75mM) to make similarly with bodily salt. The solutions of the 10 metabolites were prepared at about 100mM and pH of the solution was adjusted using K2HPO4(72mM) and KH2PO4(28mM) in H2O at pH 7.0. All measurements of MRI, MRS were made using a 3.0 T scanner (Achiva Tx 3.0 T) with SENSE - 32 channel head coil. The water signal of each volume of interest (VOI) was suppressed by variable pulse powers and optimized relaxation delays (VAPOR) applied before progress of the scan. The MRS scan parameters were as follows: point-resolved spectroscopy (PRESS) sequence; TR, 2000 ms; TE, 35 ms; shim, iterative VOI; NSA, 64. In addition, this study was conducted with jMRUI-5.0 software, with AMARES for spectral fitting. Results: Results of measured magnetic resonance imaging (MRI) factors were as follows: geometric accuracy (191.23±0.60), low contrast object detectability (28.13±0.835), image-shift distortion (0.41±0.0032). Results of measured magnetic resonance spectroscopy (MRS) factors were as follows: signal-to-noise ratio (SNR) of the NAA (25.95±0.35), water suppression percent (99.70±0.09 %), line width of water peak (5.75±0.91 Hz). Conclusion: This study was to perform QA on SVS technique using the ACR-MRS phantom which was refered ACR test guideline.The present study is being measured the quantitative accuracy of the metabolite and the accuracy of the position of the VOI which could be performed by layered shape vials. When QA protocol factors is established in this experiment, it is possible as MVS QA guideline.

Purpose: The aim of present study was to provide ex vivo evidence of changes in neurochemical profiles of rat hippocampus after acute‐binge ethanol intoxication, using high‐resolution magic angle spinning (HR‐MAS) NMR spectroscopy using a 500‐MHz spectrometer. Methods: Twenty‐male‐Wistar rats, divided into two groups (control group: n=10, binge ‐ ethanol group: n=10), were used in this study. The 10 rats in binge ‐ ethanol group received an initial ethanol dose of 5 g/kg (30% w/v solution) via oral gavage, then received additional doses of 1.5 g/kg (25% w/v solution) every 8 hours (at 1000, 1800, and 0200 hours) for 4 days. The 10 control rats received an equivalent volume of normal saline, with treatments occurring at comparable times (1100, 1900, and 0300 hours). Ex vivo 1H HR‐MAS spectroscopy was performed using an Agilent VNMRS‐500 (500.13‐MHz). One ‐ dimensional HR‐MAS spectra were acquired from all 20 tissue samples with CPMG sequence [complex data number = 16384, spectral width = 8012.8 Hz, relaxation delay time= 5.0 sec, pre‐saturation time = 2.0 sec, inter‐pulse delay (τ) = 0.4 msec, number of acquisitions = 128, and a total scan time = 15 min 24 sec]. Results: Figure 1 (A and B) shows representative 500‐MHz spectra from hippocampal regions of animals in binge ‐ ethanol and control groups. Figure 2 shows total creatine ratio levels that were quantified from 20 hippocampal tissue samples. Glutamate/tCr (**: p=0.007) and Glx/tCr (Glx: glutamine and glutamate complex [glutamate+glutamine]) (**: p=0.006) ratios were significantly higher in binge‐ethanol group than in control group. Conclusion: Our findings suggest that glutamate signals and glutamate‐glutamine cycle in hippocampal region are particularly sensitive to acute‐binge ethanol consumption. Future studies using a combination of human patients and in vivo animal MRS investigations, as well as other neuroimaging approaches, are required to strengthen our findings and to validate translational component in acute‐binge alcohol intoxicated condition.

Purpose: The cerebral metabolite changes in vivo were quantitatively assessed in binge ethanol ‐ intoxicated rats by using a 4.7‐T proton magnetic resonance spectroscopy (1H‐MRS). Methods: Thirteen 8‐week‐old, male Sprague‐Dawley rats were used and divided into 2 groups (control group: n=6; binge ‐ ethanol group: n=7). 7 binge ethanol group rats received an initial dose of 5 g/kg (30% w/v solution) via oral gavage method, followed by a maximum dose of 2 g/kg (25% w/v solution) every 8‐h (at 1400, 2200, and 0600) for 4 days. The 6 control group rats simultaneously received equal volumes (about 3.55ml) of normal saline (at 1500, 2300, and 0700). Oral gavage ethanol was administered based on body weight. After 4‐days of oral gavage, in vivo scanning was performed on all animals by using a 4.7‐T Bruker BIOSPEC. The volume of interest (VOI, 6×2×3 mm3; volume: 36 μL; Thirteen water suppressed 1H‐MRS spectra were acquired using PRESS sequences (TR/TE = 4000/20 ms; number of acquisitions = 384; number of data points = 2048). Results: Figure 1 shows the representative fitted spectra from hippocampus of binge ethanol and control group rats. Our results showed that total choline (tCho; phosphocholine+glycerophosphocholine [GPC+PCh]) concentrations were significantly lower (p=0.038) in the binge ethanol group than that in the control group (Fig.2). Moreover, tCho/total N‐acetylaspartate (tNAA: NAA+N‐acetylaspartylglutamate [NAAG]) ratios were significantly lower (p=0.043) in the binge‐ethanol group than that in the control group (Fig.3). However, Glutamine/Glutamate ratios showed no significant differences between the 2 groups. Conclusion: According to our findings and from results in previous studies, significantly low tCho concentrations and tCho/tNAA ratios may indicate the cell membrane turnover abnormalities of phosphatidylcholine and changed adaptive mechanism in the hippocampus of binge ethanol intoxicated rats. Thus, we provide quantitative in vivo evidence that binge‐ethanol exposure causes cerebral neurochemical profile changes in rats, in the hippocampal region.