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Purpose To compare in vivo glutamate-weighted chemical exchange saturation transfer (GluCEST-weighted) signal changes between in a rat model of demyelinated multiple sclerosis and control groups. Procedures Using a pre-clinical 7 T magnetic resonance imaging (MRI) system, CEST imaging was applied to a toxin (lysophosphatidylcholine; LPC) induced rat (MSLPC) and control (CTRL) groups to compare in vivo glutamate signal changes. The GluCEST-weighted signals were analyzed based on the magnetization transfer ratio asymmetry approach at 3.0 ppm on the region-of-interests (ROIs) in the corpus callosum and hippocampus at each hemispheric region. Results GluCEST-weighted signals were significantly changed between the CTRL and MSLPC groups, while higher glutamate signals were indicated in the MSLPC than the CTRL group ([MSLPC / CTRL]; hippocampus: [6.159 ± 0.790 / 4.336 ± 0.446] and corpus callosum: [-3.545 ± 0.945 / -6.038 ± 0.620], all p = 0.001). Conclusions Our results show increased GluCEST-weighted signals in the LPC-induced demyelination rat brain compared with control. GluCEST-weighted imaging could be a useful tool for defining a biomarker to estimate the glutamate-related metabolism in MS.

Aryl hydrocarbon receptor (AhR) antagonism can mitigate cellular damage associated with cerebral ischaemia and reperfusion (I/R) injury. This study investigated the neuroprotective effects of AhR antagonist administration before reperfusion in a rat stroke model and influence of the timing of AhR antagonist administration on its neuroprotective effects. Magnetic resonance imaging (MRI) was performed at baseline, immediately after, and 3, 8, and 24 h after ischaemia in the sham, control (I/R injury), TMF10 (trimethoxyflavone [TMF] administered 10 min post-ischaemia), and TMF50 (TMF administered 50 min post-ischaemia) groups. The TMF treatment groups had significantly fewer infarcts than the control group. At 24 h, the relative apparent diffusion coefficient values of the ischaemic core and peri-infarct region were significantly higher and relative T2 values were significantly lower in the TMF10 groups than in the control group. The TMF treatment groups showed significantly fewer terminal deoxynucleotidyl transferase dUTP nick-end labelling positive (+) cells (%) in the peri-infarct region than the control group. This study demonstrated that TMF treatment 10 or 50 min after ischaemia alleviated brain damage. Furthermore, the timing of AhR antagonist administration affected the inhibition of cellular or vasogenic oedema formation caused by a transient ischaemic stroke.

To evaluate the effects of a reference image and keyhole factor (Kf) selections for high-frequency substitution on keyhole imaging technique for applications in glutamate chemical exchange saturation transfer (GluCEST) imaging. The CEST data were obtained using a 7.0 T MRI scanner. We used varied Kf ranges that constituted from 16.67 to 75 % of the full k-space. The reference image was respectively selected for − 3 and + 3 ppm images that associated with the GluCEST calculation and the unsaturated image. The zero-padding algorithm was applied for the missing k-space lines in the low-frequency data collected to compare the results obtained from using the keyhole imaging technique. All the techniques were evaluated using a healthy rat group and extended to the status epilepticus rat group to explore their applicability and usability. The calculated GluCEST signals and visually inspected results from the reconstructed GluCEST maps indicated that the combination of unsaturated image as a reference image, and over 50 % of Kf showed consistent signals and image quality compared with the fully sampled CEST data. Combining the keyhole imaging technique with GluCEST imaging enables stable image reconstruction and quantitative evaluation, and this approach is potentially applicable in various CEST imaging applications.

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

Aryl hydrocarbon receptors (AhRs) have been reported to be important mediators of ischemic injury in the brain. Furthermore, the pharmacological inhibition of AhR activation after ischemia has been shown to attenuate cerebral ischemia-reperfusion (IR) injury. Here, we investigated whether AhR antagonist administration after ischemia was also effective in ameliorating hepatic IR injury. A 70% partial hepatic IR (45-minute ischemia and 24-hour reperfusion) injury was induced in rats. We administered 6,2',4'-trimethoxyflavone (TMF, 5 mg/kg) intraperitoneally 10 minutes after ischemia. Hepatic IR injury was observed using serum, magnetic resonance imaging-based liver function indices, and liver samples. TMF-treated rats showed significantly lower relative enhancement (RE) values and serum alanine aminotransferase (ALT) and aspartate aminotransferase levels than did untreated rats at three hours after reperfusion. After 24 hours of reperfusion, TMF-treated rats had significantly lower RE values, ΔT1 values, serum ALT levels, and necrotic area percentage than did untreated rats. The expression of the apoptosis-related proteins, Bax and cleaved caspase-3, was significantly lower in TMF-treated rats than in untreated rats. This study demonstrated that inhibition of AhR activation after ischemia was effective in ameliorating IR-induced liver injury in rats.

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.

To evaluate the feasibility of motion correction in glutamate chemical exchange saturation transfer (GluCEST) imaging, using a rat model of epileptic seizure. Epileptic seizure was induced in six male Wistar rats by intraperitoneal injection of kainic acid (KA). CEST data were obtained using a 7.0 T Bruker MRI scanner before and 3 h after KA injection. Retrospective motion correction was performed in CEST images using a gradient-based motion correction (GradMC) algorithm. GluCEST signals in the hippocampal regions were quantitatively evaluated with and without motion correction. Calculated GluCEST signals differed significantly between the pre-KA injection group, regardless of motion-correction implementation, and the post-KA injection group with motion correction (3.662 ± 1.393 % / 3.726 ± 1.982 % for pre-KA injection group with/without motion correction vs. 6.996 ± 1.684 % for post-KA injection group with motion correction; all P

Background Investigations of amide proton signal changes in the white matter of demyelinating diseases may provide important biophysical information for diagnostic and prognostic assessments. Purpose To evaluate amide proton signals in cuprizone-induced rats using amide proton transfer-weighted (APTw) MRI, which provides in vivo image contrast by changing amide proton concentrations during demyelination (DEM) and subsequent remyelination (REM). Materials and Methods In this animal study, APTw 7-T MRI was performed in 21 male Wistar rats divided into cuprizone-induced (n = 14) and control (n = 7) groups from February to August 2020. The cuprizone-induced group was further subdivided into DEM (n = 7) and REM (n = 7) groups. Seven weeks after cuprizone feeding, rats in the DEM group were killed prior to transmission electron microscopy and myelin staining, while rats in the REM group were changed to a normal chow diet and fed for 5 weeks. In each group, the APTw signals were calculated using a conventional magnetization transfer ratio at 3.5 ppm based on regions of interest in the corpus callosum. Statistical differences in APTw signals among the groups were analyzed with one-way analysis of variance followed by Tukey post hoc tests. Results The mean APTw signals in the control and DEM groups were -4.42% ± 0.60 (standard deviation) (95% CI: -4.98, -3.86) and -2.57% ± 0.48 (95% CI: -3.01, -2.12), respectively, indicating higher in vivo APTw signals in the DEM lesion (P < .001). After REM, mean APTw signal in the REM group was -3.83% ± 0.67 (95% CI: -4.45, -3.22), similar to that in the control group (P = .18) and lower than that in the DEM group (P < .001). Conclusion Significant amide proton transfer-weighted (APTw) metric changes coupled with the histologic characteristics of the demyelination and remyelination processes indicate the potential usefulness of APTw 7-T MRI to monitor earlier myelination processes. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by van Zijl in this issue.

Background: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. Method: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. Results: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (&minus, 7.25 &plusmn, 1.42% vs. &minus, 2.84 &plusmn, 1.30%, p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (&minus, 6.52 &plusmn, 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). Conclusion: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process.

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 &le, 0.001) between the corpus callosum (&minus, 1.71 &plusmn, 1.04%, white matter) and other brain regions (3.59 &plusmn, 0.41%, cortex, 5.47 &plusmn, 0.61%, hippocampus, 4.49 &plusmn, 1.11%, rest of midbrain, gray matter). The stability test of GluCEST findings for each brain region was not significantly different (all p &ge, 0.263). In line with the GluCEST results, glutamate concentrations measured by 1H MRS also appeared higher in the hippocampus (7.30 &plusmn, 0.16 &mu, mol/g) than the cortex (6.89 &plusmn, 0.72 &mu, mol/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.

To evaluate the effects of a reference image and keyhole factor (KThe CEST data were obtained using a 7.0 T MRI scanner. We used varied KThe calculated GluCEST signals and visually inspected results from the reconstructed GluCEST maps indicated that the combination of unsaturated image as a reference image, and over 50 % of KCombining the keyhole imaging technique with GluCEST imaging enables stable image reconstruction and quantitative evaluation, and this approach is potentially applicable in various CEST imaging applications.

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.

To evaluate signal changes in the hippocampus of epileptic seizure rat models, based on quantified creatine chemical exchange saturation transfer (CrCEST) signals. CEST data and 1H magnetic resonance spectroscopy (1H MRS) data were obtained for the two imaging groups: control (CTRL) and epileptic seizure-induced (ES; via kainic acid [KA] injection) groups. CrCEST signals in the hippocampal regions were quantitatively evaluated; correlations between CrCEST signals and phosphocreatine (PCr) and total creatine (tCr; PCr + Cr) concentrations, derived from the analysis of 1H MRS data, were investigated as a function of time changes (before KA injection, 3 and 5 h after KA injection). Measured CrCEST signals were exhibited significant differences between before and after KA injection in the ES group. At each time point, CrCEST signals showed significant correlations with PCr concentration (all |r| > 0.59; all P 0.05). CrCEST can adequately detect changes in the concentration of Cr as a result of energy metabolism, and may serve as a potentially useful tool for diagnosis and assessment of prognosis in epilepsy.

To evaluate the effects of signal intensity differences between the b0 image and diffusion tensor imaging (DTI) in the image registration process. To correct signal intensity differences between the b0 image and DTI data, a simple image intensity compensation (SIMIC) method, which is a b0 image re-calculation process from DTI data, was applied before the image registration. The re-calculated b0 image (b0ext) from each diffusion direction was registered to the b0 image acquired through the MR scanning (b0nd) with two types of cost functions and their transformation matrices were acquired. These transformation matrices were then used to register the DTI data. For quantifications, the dice similarity coefficient (DSC) values, diffusion scalar matrix, and quantified fibre numbers and lengths were calculated. The combined SIMIC method with two cost functions showed the highest DSC value (0.802 ± 0.007). Regarding diffusion scalar values and numbers and lengths of fibres from the corpus callosum, superior longitudinal fasciculus, and cortico-spinal tract, only using normalised cross correlation (NCC) showed a specific tendency toward lower values in the brain regions. Image-based distortion correction with SIMIC for DTI data would help in image analysis by accounting for signal intensity differences as one additional option for DTI analysis. • We evaluated the effects of signal intensity differences at DTI registration. • The non-diffusion-weighted image re-calculation process from DTI data was applied. • SIMIC can minimise the signal intensity differences at DTI registration.

Magnetic resonance imaging and spectroscopy (MRI-MRS) is a useful tool for the identification and evaluation of chemical changes in anatomical regions. Quality assurance (QA) is performed in either images or spectra using QA phantom. Therefore, consistent and uniform technical MRI-MRS QA is crucial.Here we developed an MRI-MRS fused phantom along with the inserts for metabolite quantification to simultaneously optimize QA parameters for both MRI and MRS. T1- and T2-weighted images were obtained and MRS was performed with point-resolved spectroscopy.Using the fused phantom, the results of measuring MRI factors were: geometric distortion,2% and ± 2 mm; image intensity uniformity, 83.09 ± 1.33%; percent-signal ghosting, 0.025 ± 0.004; low-contrast object detectability, 27.85 ± 0.80. In addition, the signal-to-noise ratio of N-acetyl-aspartate was consistently high (42.00 ± 5.66).In previous studies, MR phantoms could not obtain information from both images and spectra in the MR scanner simultaneously. Here we designed and developed a phantom for accurate and consistent QA within the acceptance range. It is important to take into account variations in the QA value using the MRI-MRS phantom, when comparing to other clinical or research MR scanners.The MRI-MRS QA factors obtained simultaneously using the phantom can facilitate evaluation of both images and spectra, and provide guidelines for obtaining MRI and MRS QA factors simultaneously.

Rationale and Objectives Variation in tissue damage after cerebral ischemia/reperfusion (I/R) can cause uncertainty in stroke-related studies, which can be reduced if the damage can be predicted early after ischemia by measuring the apparent diffusion coefficient (ADC). We investigated whether ADC measurement in the acute phase can predict permanent cerebral I/R injury. Materials and Methods The middle cerebral artery occlusion model was established using the intraluminal suture method to induce 60 minutes of ischemia followed by reperfusion in rats. T2-weighted images and diffusion-weighted images were obtained at 30 minutes and 24 hours after ischemia. Neuronal cell survival was assessed by neuronal nuclei (NeuN) immunofluorescence staining. The correlation between relative ADC (rADC) values at 30 minutes and I/R injury at 24 hours after ischemia was analyzed. Magnetic resonance imaging results were confirmed by histologic analysis. Results The correlation between rADC values at 30 minutes and 24 hours was strong in the ischemic core and peri-infarct region but moderate in the anterior choroidal and hypothalamic region. Histologic analysis revealed that the correlation between rADC values at 30 minutes and the number of NeuN-positive cells at 24 hours was strong in the ischemic core and peri-infarct region but moderate in the anterior choroidal and hypothalamic region. Furthermore, there was a strong positive correlation between the sum of rADC values of three regions at 30 minutes and the infarct volume at 24 hours. Conclusion ADC measurement in the acute phase can predict permanent cerebral I/R injury and provide important information for the evaluation of ischemic stroke.

Purpose To evaluate temporal changes in gamma-aminobutyric acid (GABA) signals in the hippocampus during epileptiform activity induced by kainic acid (KA) in a rat model of status epilepticus using chemical exchange saturation transfer (CEST) imaging technique. Methods CEST imaging and 1H magnetic resonance spectroscopy (1H MRS) were applied to a systemic KA-induced rat model to compare GABA signals. All data acquisition and analytical procedures were performed at three different time points (before KA injection, and 1 and 3 h after injection). The CEST signal was analyzed based on regions of interests (ROIs) in the hippocampus, while 1H MRS was analyzed within a 12.0 μL ROI in the left hippocampus. Signal correlations between the two methods were evaluated as a function of time change up to 3 h after KA injection. Results The measured GABA CEST-weighted signal intensities of the rat epileptic hippocampus before injection showed significant differences from those after (averaged signals from both hippocampi: 4.37% ± 0.87% and 7.305 ± 1.11%; P 0.05). In contrast, the correlation between the CEST imaging values and 1H MRS was significant (r ≥ 0.64; P Conclusions GABA signal changes during epileptiform activity in the rat hippocampus, as detected using CEST imaging, provided a significant contrast according to changes in metabolic activity. Our technical approach may serve as a potential supplemental option to provide biomarkers for brain disease.

The aim of this study was to evaluate the transverse relaxation time of methylene resonance as compared to other lipid resonances. The examinations were performed using a 3.0 T scanner with a point-resolved spectroscopy (PRESS) sequence. Lipid relaxation time in a lipid phantom filled with canola oil was estimated with a repetition time (TR) of 6000ms and echo time (TE) of 40-550ms. For in vivo proton magnetic resonance spectroscopy ((1)H-MRS), eight male Sprague-Dawley rats were given free access to a normal-chow (NC) and another eight male Sprague-Dawley rats were given free access to a high-fat (HF) diet. Both groups drank water ad libitum. T2 measurements in the rats' livers were conducted at a fixed TR of 6000ms and TE of 40-220ms. Exponential curve fitting quality was calculated through the coefficients of determination (R(2)). Chemical analyses of the phantom and livers were not performed, but T2 decay curves were acquired. The T2 relaxation time of methylene resonance was estimated as follows: NC rats, 37.1±4.3ms; HF rats, 31.4±1.8ms (p

To identify the hand and foot fibre tracts of the corticospinal tract (CST), and to evaluate the relative locations, angles, and distances of two fibre tracts using diffusion tensor tractography (DTT). Twelve healthy subjects were enrolled. The regions of interests (ROIs) were drawn in the functional magnetic resonance imaging (fMRI) activation areas and pons in each subject for fibre tracking. We evaluated fibre tract distributions using distances and angles between two fibre tracts starting from the location of a hand fibre tract in multiple brain regions. The measured angles and distances were 96.43–150°/2.69–9.93 mm (upper CR), 91.86–180°/1.63–7.42 mm (lower CR), 54.47–75°/0.75-4.45 mm (PLIC), and 3.65–90°/0.11–2.36 mm (pons), respectively. The distributions between CR and other sections, such as PLIC and pons, were statistically significant (p

The primary goal of this study was to quantitatively assess regional changes in function and pathophysiological characteristics in renal ischemia/reperfusion (IR)-injured mice and compare data obtained at baseline and following injury. The second goal was to correlate blood oxygenation level-dependent (BOLD) and diffusion tensor imaging (DTI) data obtained in renal IR-injured mice at baseline using time-dependent scans. The analyses were conducted using a mouse model of IR injury. T2*, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) values were acquired to pathophysiologically evaluate three renal regions. The T2* values obtained in the renal cortex and medulla demonstrated no significant differences between baseline and after IR injury. According to DTI results, ADC values in both renal regions were significantly lower at 0 h, and then gradually increased within 48 h. The FA values of both renal regions decreased at 0 h, and then gradually increased by 8 h after IR injury. BOLD and DTI correlations were not significant in renal cortex. However, significantly positive correlations were found between baseline and time-dependent data obtained from renal medulla of IR-injured kidneys. Our current findings suggest that magnetic resonance imaging could be used to obtain pathophysiological data from separate renal compartments in IR-injured mice. Hence, BOLD and DTI may also provide functional and pathophysiological data on allograft status following kidney transplant without the need to use a contrast agent.

Ethanol is the most commonly abused intoxicating substance among young and middle-aged adults, and ranks highly as a cause of disability and mortality. A pattern of heavy consumption, called binge drinking, leads to various psychiatric disorders. However, to the best of our knowledge, assessments of the influence of short-term binge ethanol (SBE) intoxication on cerebral metabolite changes in human and rat models are scarce. We used in vivo 1H magnetic resonance spectroscopy (1H-MRS) to quantitatively assess neurochemical responses in hippocampus in a rat model of SBE intoxication. Seven SBE-exposed rats received an initial dose of 5.0-g/kg ethanol (30 %-w/v solution) through gavage and additional doses of 2.0-g/kg ethanol (25 %-w/v solution), every 8 hour for 4 days. Six rats in sham control group (CNTL) received an equivalent volume of distilled water at comparable times. Sixty minutes after last gavage session, in vivo 1H-MRS scans were obtained from all rats using a 4.7 Tesla animal scanner. For neurochemical analysis, a single voxel was positioned in the hippocampal region and spectra were fitted for the quantification of 17 cerebral neurochemical signals. In hippocampus, the concentration of total choline-containing compound signals (tCho: [glycerophosphocholine] + [phosphocholine]) was significantly lower in SBE-exposed rats than in CNTL rats. Moreover, gamma-aminobutyric acid (GABA)/total creatine (tCr: creatine + phosphocreatine), tCho/tCr, and tCho/total N-acetyl-aspartate (tNAA: N-acetyl-aspartate + N-acetyl-aspartyl-glutamate) ratios were significantly lower in SBE-exposed rats than CNTL rats. We determined that tCho, GABA, and tNAA signals were highly sensitive to short-term binge ethanol intoxication, which provides insights into neurochemical alterations associated with ethanol abuse.

Although diffusion tensor imaging (DTI) has been widely used for the quantitative analyses of the integrity of white matter in the brain in clinical and research fields, quality assurance (QA) for DTI has not been fully established. Thus, we suggest a QA guideline for DTI using the American College of Radiology (ACR) Magnetic resonance imaging (MRI) head phantom. In this study, the geometric accuracy, slice-position accuracy, image intensity uniformity, percent signalghosting, low-contrast object detectability, image distortion, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were measured and evaluated in 1.5T and 3.0T MRI scanners equipped with an 8-channel SENSE head coil. The standard axial spin echo (SE) T1-weighted MR images and DTI with 6, 15 and 32 directions were obtained. Concerning geometric accuracy, image twisting in the three directions was observed due to the inhomogeneity of echo planar imaging (EPI). Image intensity uniformity was significantly lower for DTI than for the standard SE T1-weighted MR images. Percent signal ghosting was higher for images from 3.0T MRI than for images from 1.5T MRI. Low-contrast object detectability was visually identified and measured at a low contrasttonoise ratio (CNR) and a low signaltonoise ratio (SNR). Image distortion changed remarkably to the phaseencoding direction. The present study using the ACR MRI phantom suggests a QA method for DTI with high reproducibility and easy accessibility.

In this work, we present the feasibility of using a parallel RF transmit with multiple RF sources imaging method (MultiTransmit imaging) in polymer gel dosimetry. Image quality and B1 field homogeneity was statistically better in the MultiTransmit imaging method than in conventional single source RF transmission imaging method. In particular, the standard uncertainty of R 2 was lower on the MultiTransmit images than on the conventional images. Furthermore, the MultiTransmit measurement showed improved dose resolution. Improved image quality and B1 homogeneity results in reduced dose uncertainty, thereby suggesting the feasibility of MultiTransmit MR imaging in gel dosimetry.

Gamma-animobutyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. Deficits in GABA-containing neurons are consistently reported in psychiatric disease, particularly in the prefrontal cortex and hippocampus. Repetitive transcranial magnetic stimulation (rTMS) that use magnetic field to stimulate focal cortical regions with electrical current have a potential therapeutic effects with non-invasive and painless method. In this study, we used chronic unpredictable mild stress (CUMS) rat model of depression to investigate the behavioral and neurochemical alterations. Furthermore, chronic rTMS treatment effect on neurochemical profile in prefrontal cortex and hippocampus of rats were assessed. The CUMS induced significant reductions in absolute sucrose intake and sucrose preference. In addition, high-resolution (1)H-NMR spectra from brain extracts revealed significantly reduced prefrontal and hippocampal GABA levels in CUMS rats compared to control. The behavioral and neurochemical changes were reversed by chronic rTMS treatment. Furthermore, chronic rTMS treatments results in differential effects on different brain regions. Our results suggest specific and regionally different metabolic response to chronic rTMS treatment in animal model of depression.

The aim of this study was to quantitatively assess the effects of short-term intermittent ethanol intoxication on cerebral metabolite changes among sham controls (CNTL), low-dose ethanol (LDE)-exposed, and high-dose ethanol (HDE)-exposed rats, which were determined with ex vivo high-resolution spectra. Eight-week-old male Wistar rats were divided into three groups. Twenty rats in the LDE ( n = 10) and the HDE ( n = 10) groups received ethanol doses of 1.5 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 1 H nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the three groups). Normalized total N -acetylaspartate (tNAA: NAA + NAAG [ N -acetylaspartyl-glutamate]), 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 six 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 (−). Our results suggested that short-term 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 1 H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of short-term intermittent ethanol intoxication in the frontal cortex.

In megavoltage X-ray imaging (MVI), computed radiography (CR) has required a very simple and general quality assurance (QA) method based on a radiotherapy imaging technique. The purpose of this study was to develop a general QA method for evaluating the modulation transfer function (MTF), the noise power spectrum (NPS) and the detective quantum efficiency (DQE) for MVI. Thus, a simple and compact edge block made of tungsten, with dimensions of 19 × 10 × 1 cm3, was efficiently designed and developed. The pre-sampling MTF was evaluated with the following settings: a 6 megavoltage (MV) energy, four different types of detectors, CR-IP (image plate: photo-stimulable phosphor screen), CR-IP-Lead (image plate + lead screen), CR-IP-Regular (fast front screen + image plate + fast front screen) and CR-IP-Fast (fast back screen + image plate + fast front screen). The MTF values at 1 mm−1 for CR-IP-Regular showed the highest resolution of 0.18. The best noise distribution was observed in the measurement of the NPS with CR-IP-Regular. With increasing spatial frequency, our results showed that value of the DQE for the four types of detectors was approximately 1.0 mm−1, which is comparable to the values reported in the literature. In this report, measurements for megavoltage imaging based on line-pair modulations by using an edge block are presented. When the wide side of the tungsten block was reduced, the accuracy of the edge measurement was improved to match those offered by edge techniques. The present study demonstrates that the QA method with our home-made edge block can be used to evaluate the MTF, NPS and DQE for MVI.

Overweight and obesity may significantly worsen glycaemic and metabolic control in type 2 diabetes. However, little is known about the effects of overweight and obesity on the brains of people with type 2 diabetes. Here, we investigate whether the presence of overweight or obesity influences the brain and cognitive functions during early stage type 2 diabetes. This study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in their brain structures and cognition during early stage type 2 diabetes compared with participants with normal weight. Relationships between each of these measures and disease duration were also examined. Global mean cortical thickness was lower in the overweight/obese type 2 diabetes group than in the normal-weight type 2 diabetes group (z = −2.96, p for group effect = 0.003). A negative correlation was observed between disease duration and global mean white matter integrity (z = 2.42, p for interaction = 0.02) in the overweight/obese type 2 diabetes group, but not in the normal-weight type 2 diabetes group. Overweight/obese individuals with type 2 diabetes showed a decrease in psychomotor speed performance related to disease duration (z = −2.12, p for interaction = 0.03), while normal-weight participants did not. The current study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in brain structures and cognition during early stage type 2 diabetes compared with normal-weight participants.

The aim of present study was to quantitatively investigate the neurochemical profile of the frontal cortex region in a rat model of long-term alcohol consumption, by using in vivo proton magnetic resonance spectroscopy ((1)H-MRS) at 4.7 T and ex vivo(1)H high-resolution magic angle spinning (HR-MAS) technique at 11.7 T. Twenty male rats were divided into two groups and fed a liquid diet for 10 weeks. After 10 weeks, in vivo(1)H MRS spectra were acquired from the frontal cortex brain region. After in vivo(1)H MRS experiments, all animals were sacrificed and 20 frontal cortex tissue samples were harvested. All tissue examinations were performed with the 11.7 T HR-MAS spectrometer and high-resolution spectra were acquired. The in vivo and ex vivo spectra were quantified as absolute metabolite concentrations and normalized ratios of total signal-intensity (i.e., metabolitesNorm), respectively. The absolute quantifications of in vivo spectra showed significantly higher glycerophosphocholine plus phosphocholine (GPC+PCh) and lower myo-inositol (mIns) concentrations in ethanol-treated rats compared to controls. The quantifications of ex vivo spectra showed significantly higher PChNorm, ChoNorm and tChoNorm, and lower GPCNorm and mInsNorm ratio levels in ethanol-treated rats compared to controls. Our findings suggest that reduced mIns concentrations caused by the long-term alcohol consumption may lead to hypo-osmolarity syndrome and astrocyte hyponatremia. In addition, increased choline-containing compound concentrations may reflect an increased cell turnover rate of phosphatidylcholine and other phospholipids, indicating an adaptive mechanism. Therefore, these results might be utilized as key markers in chronic alcohol intoxication metabolism.

Neuroprotective therapeutics slows down the degeneration process in animal models of Parkinson’s disease (PD). The neuronal survival in PD animal models is often measured by using immunohistochemistry. However, dynamic changes in the pathology of the brain cannot be explored with this technique. Application of in-vivo 1H magnetic resonance spectroscopy (1H MRS) can cover this shortcoming, as these techniques are non-invasive and can be repeated over time in the same animal. Thus, the sensitivity of both techniques to measure changes in the PD pathology was explored in an experiment studying the neuroprotective effects of the vigilance enhancer bee-venom (BV) in a mouse model of PD. The mice were pre-treated with 0.02-ml BV administered to the acupuncture point GB34 (Yangneungcheon) once every 3 days for 2 weeks. Three groups were classified as control, MPTP-intoxicated PD model and BV-treated mice. Outer volume suppression combined with the ultra-short echo-time STEAM (TE = 2.2 ms, TM = 20 ms, TR = 5000 ms) was used for localized in-vivo 1H MRS. Based on the 1H MRS spectral analysis, substantial changes of the neurochemical profiles were evaluated in the three investigated groups. In particular, the glutamate complex (Glx)/creatine (Cr) ratio (7.72 ± 1.25) in the PD group was significantly increased compared to that in the control group (3.93 ± 2.21, P = 0.001). Compared to the baseline values, the Glx/Cr ratio of the BV-treated group was significantly decreased 2 weeks after MPTP intoxication (one-way ANOVA, p < 0.05). In conclusion, the present study demonstrated that neurochemical alterations occurred in the three groups and that the neuroprotective effects of the BV acupuncture in a mouse model of PD could be quantified by using immunohistochemistry and 1H MRS.

BACKGROUND The metabolite response during a memory task in Alzheimer's disease (AD) patients is unknown. OBJECTIVE To investigate the metabolite changes in subjects with AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) elderly during a memory task using functional magnetic resonance spectroscopy (fMRS). METHODS This study involved 23 young normal controls (YC), 24 CN elderly, 24 aMCI, and 24 mild and probable AD individuals. fMRS data were acquired at the precuneus and posterior cingulate brain regions during a face-name association task. Statistical analyses of quantified metabolites were performed to evaluate differences of the metabolite values between the stimulation conditions and among the four subject groups. Receiver operating curve analysis was performed to evaluate whether the metabolic changes after functional activations can differentiate the subject groups. RESULT Glutamine and glutamate complex (Glx) was statistically significantly different between the fixation and repeat conditions in aMCI (p = 0.0492) as well as between the fixation and the novel conditions in the AD (p = 0.0412) group. The total N-acetylaspartate (tNAA) was statistically significantly different among the four subject groups in the fixation condition (DF = 3, F = 7.673, p < 0.001), the novel condition (DF = 3, F = 6.945, p < 0.001), and the repeat condition (DF = 3, F = 7.127, p < 0.001). tNAA, tCr, and mIns could be used to differentiate CN from aMCI. Furthermore, tNAA, tCr, Glx, and Glu could also differentiate CN from AD, and aMCI from AD. CONCLUSION Glx was altered during a stimulation that may be used to evaluate neuronal dysfunction in a demented patient. tNAA and tCr were reduced in patients with AD.

Repeated exposure to dizocilpine (MK-801) can be used as a model of schizophrenia that incorporates disease progression. Proton magnetic resonance spectroscopy ( 1 H MRS) has been widely used to investigate schizophrenia-related alterations in glutamate (Glu). The purpose of this study was to investigate metabolic alterations in the prefrontal cortex (PFC) in an animal model of schizophrenia by using in vivo 1 H MRS. Because of the spectral overlap of Glu and glutamine (Gln), high-field 1 H MRS with short echo time (TE) was used. A point-resolved spectroscopy sequence was used to measure the levels of Glu and Gln, and the brain metabolites in a volume of interest (22.5 μL) located in the PFC region of rats (n = 13) before and after 6 days of MK-801 (0.5 mg/kg) treatment. Analysis of the spectra showed that the cross-contamination of Glu and Gln can be considered to comparably low. No metabolic parameters were altered ( p > 0.05). However, differences in Glu and N-acetylaspartate (NAA) levels between two times were significantly correlated ( p 1 H MRS can quantify Glu and Gln with reliably low level of cross-contamination and that repeated exposure to MK-801 induces the progressive development of schizophrenia.

The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue. In the right dorsal hippocampal region, the gamma-aminobutyric-acid (GABA) and glutamine (Gln) concentrations were significantly higher in the sleep-perturbed rats than in the sham controls. The ratios of Gln/Glu (glutamate), Gln/tCr (total-creatine), and GABA/Glu were also significantly higher in the sleep-perturbed group, while serotonin concentrations were significantly lower in the sleep-perturbed rats. Pearson correlation results among individual rat data indicate that concentrations of dopamine (DA) and serotonin (5-HT) were significantly higher in SSP rats. A larger correlation coefficient was also observed for the SSP rats. Analysis of the correlation between the in vivo and in vitro signals indicated that the concentrations of Gln, 5-HT, and DA exhibited a significant negative correlation in the SSP rat data but not in that of control rats. The authors propose that the altered and correlated GABA, Gln, 5-HT, and DA concentrations/ratios could be considered key markers of neurological function in animal models of stress-induced sleep perturbation.

The purpose of this study is to acquire accurate diffusion tensor tractography (DTT) results for arcuate fasciculus (AF) fiber tract using Brodmann's area (BA) template for region of interest (ROI) setting. Thirteen healthy subjects were participated in this study. Fractional anisotropy (FA) map of each subject was calculated using diffusion tensor data, and T1w template was co-registered to FA map. The BA template was also co-registered using the transformation matrix. The ROIs were drawn in the co-registered BA template, and AF fiber tract was extracted. To generate the probabilistic pathway map, a binary mask image was generated based on the fiber tract image and co-registered to T1w template image. We also measured relative location of the AF fiber tract. The location of the probabilistic pathway map of each subject's AF fiber tract was well defined in the brain. By using this probabilistic map, the mediolateral position ratio of AF was measured 18%, and the anteroposterior position ratio of AF was measured 35%, respectively. This study demonstrated that the AF fiber tract can be extracted using BA template for ROI setting and probabilistic pathway of fiber tract. Our results and analytical approaches can helpful for accurate fiber tracking and application of perspective clinical researches.

The noise power spectrum (NPS) is one of the most general methods for measuring the noise amplitude and the quality of an image acquired from a uniform radiation field. The purpose of this study was to compare different NPS methodologies by using megavoltage X-ray energies. The NPS evaluation methods in diagnostic radiation were applied to therapy using the International Electrotechnical Commission standard (IEC 62220-1). In order to measure the region of interest (ROI) of the NPS, we used the following five factors: the overlapping impact, the non-overlapping impact, the penumbra, the flatness and different ROI sizes. We used NPS from four different types of detectors, the CR-IP (computed radiography image plate: photo-stimulable phosphor screen), the CR-IP-lead (hexalon lead screen), the CR-IP-back [lanex TM fast back screen: {terbium-doped gadolinium oxysulfide granular phosphor screen (Gd2O2S:Tb,133 mg/cm2)} + 1-mm-thick copper plate and the CR-IP-front (lanex TM fast front screen). A Kodak 2000 RT photo-stimulable phosphor-based computed radiographic (CR) system showed that the normalized noise power spectrum (NNPS) curve gradually decreased, in compliance with increasing spatial resolution. In addition, each detector showed a different reactivity of the NPS to megavoltage. The results of multivariate analysis of variance (MANOVA) test (methods × detectors) revealed significant main effects of the methods [F(1, 4) = 53.543, P = 0.001 and of the detectors [F(1, 4) = 17.556, P = 0.001]. The present study revealed that various factors could be employed to produce megavoltage imaging (MVI) of the NPS and as a baseline standard for NPS control in MVI.

It is well known that a variety of stressors induces a significant alteration in various putative neurotransmitters in the mammalian CNS. However, relatively little attention has been paid on the alteration of central glutamate neurotransmission, which is a major excitatory neurotransmitter in the brain. The present study aimed to determine whether acute restraint stress induces the changes in neurotransmitter level, especially glutamate, in rat brain and to examine whether 1-h recovery time after the termination of stress can revert to its pre-stress state. In vivo 1H-NMR spectra were acquired from the cerebral cortex and hippocampus (control: N = 10, stress: N = 10, stress + 1 h rest: N = 10) immediately or after 1 h rest from restraint stress. All in vivo proton spectra were automatically analyzed using LCModel. We found that acute restraint stress induced significant increase in glutamate concentrations in the cerebral cortex and the hippocampus of rat. However, the level could not revert to its pre-stress state by the end of 1-h recovery period in cerebral cortex of rats. In addition, glutamine/glutamate ratio, which may function as an index of the glutamatergic neurotransmission, was significantly lower in the cerebral cortex of both stress and 1 h stress + 1 h recovery groups, as compared to control. Our finding may provide important evidence for altered glutamatergic activity after the stress and suggest a potential biochemical marker for eventual diagnosis and/or therapy monitoring in mood disorder.

The 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopamine system in rat can develop neuropathological and neurochemcial changes similar to those seen in patients with Parkinson’s disease (PD). The purpose of this study was to test the hypothesis that the N-acetylaspartate level (NAA), regarded as neuronal marker would be decreased after 6-OHDA lesions in rat brain and to determine whether metabolic alteration are correlated with behavioral deficit. The animals were undergone adjusting stepping test and proton magnetic resonance spectroscopy (1H-MRS). In vivo 1H-NMR spectra (TR/TE = 2500/144 ms) were acquired from both left (contralateral region) and right striatum (ipsillateral region). There was a highly significant impairment in left forepaw performance and significant reductions in NAA/total creatine (tCr) ratios were observed in the ipsillateral striatum of rat (P < 0.05). Furthermore, there was a significant correlation between left forepaw performance and NAA/tCr level on the whole sample (Spearman correlation test, ρ = 0.634, P = 0.011). Our results suggest that the NAA/tCr ratio may be a valuable criterion for evaluation of functional impairment of the striatum in 6-OHDA rat model of PD.