Explore the vast range of titles available.

Abstract Gliomatosis cerebri (GC) represents an antemortem diagnostic challenge in the absence of histopathology. Proton magnetic resonance spectroscopy (1H-MRS) features of the disease in humans include elevated myo-inositol (mI)-to-creatine and decreased N-acetyl-aspartate (NAA)-to-creatine ratios. Brain 1H-MRS findings at 3 Tesla (3 T) field strength in dogs with GC have not yet been described. A 12-year-old West Highland White Terrier was presented with a progressive history of multifocal encephalopathy. A 3 T MRI revealed a diffuse, bilateral, ill-defined, intra-axial white matter lesion that was T2W and FLAIR hyperintense, T1W iso- to hypointense, showed no contrast enhancement, and was associated with moderate mass effect. 1H-MRS with voxel positioning at the left parietal area showed highly elevated mI and decreased NAA levels compared to healthy control dogs measured using the same protocol in the thalamus. GC was confirmed by stereotactic brain biopsy. Comparable 1H-MRS changes to those reported in humans were identified in a dog with GC.

•The reproducibility assessment of magnetic resonance spectroscopy was explored.•CV and ICC showed good reliability of within- and between- scanning sessions.•Bland-Altman plots indicated strong agreement in the repeated measurements.•Pearson correlation coefficients showed great reproducibility across three machines.•It revealed higher reproducibility for the intra-vendor than the inter-vendor. Proton magnetic resonance spectroscopy (1H-MRS) has potential in clinical diagnosis and understanding the mechanism of illnesses. However, its application is limited by the lack of standardization in data acquisition and processing across time points and between different magnetic resonance imaging (MRI) system vendors. This study examines whether metabolite concentrations obtained from different sessions, scanner models, and vendors can be reliably reproduced and combined for diagnostic analysis-an important consideration for rare disease research. Participants underwent magnetic resonance scanning once on two separate days within one week (one session per day, each including two 1H-MRS scans without subject movement) on each machine. Absolute metabolite concentrations were analyzed for reliability of within- and between- session using the coefficient of variation (CV), intraclass correlation coefficient (ICC) and Bland-Altman (BA) plot, and for reproducibility across the machines using the Pearson correlation coefficient. As for within- and between- session, most of the CV values for a group of all the first or second scans of a session, and from each session were below 20 %, and most of ICCs ranged from moderate (0.4≤ICC<0.59) to excellent (ICC≥0.75), which indicated high reliability. Most of the BA plots had the line of equality between 95 % confidence interval of bias (mean difference), therefore the differences over scanning time could be negligible. Majority of the Pearson correlation coefficients approached 1 with statistical significance (P < 0.001), showing high reproducibility across the three scanners. Additionally, the intra-vendor reproducibility was greater than the inter-vendor ones. [Display omitted]

Abstract The variability in the response to antipsychotic medication in schizophrenia may reflect between-patient differences in neurobiology. Recent cross-sectional neuroimaging studies suggest that a poorer therapeutic response is associated with relatively normal striatal dopamine synthesis capacity but elevated anterior cingulate cortex (ACC) glutamate levels. We sought to test whether these measures can differentiate patients with psychosis who are antipsychotic responsive from those who are antipsychotic nonresponsive in a multicenter cross-sectional study. 1H-magnetic resonance spectroscopy (1H-MRS) was used to measure glutamate levels (Glucorr) in the ACC and in the right striatum in 92 patients across 4 sites (48 responders [R] and 44 nonresponders [NR]). In 54 patients at 2 sites (25 R and 29 NR), we additionally acquired 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) to index striatal dopamine function (Kicer, min−1). The mean ACC Glucorr was higher in the NR than the R group after adjustment for age and sex (F1,80 = 4.27; P = .04). This was associated with an area under the curve for the group discrimination of 0.59. There were no group differences in striatal dopamine function or striatal Glucorr. The results provide partial further support for a role of ACC glutamate, but not striatal dopamine synthesis, in determining the nature of the response to antipsychotic medication. The low discriminative accuracy might be improved in groups with greater clinical separation or increased in future studies that focus on the antipsychotic response at an earlier stage of the disorder and integrate other candidate predictive biomarkers. Greater harmonization of multicenter PET and 1H-MRS may also improve sensitivity.

Aims This study employed diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (1H‐MRS) on an MPTP‐induced mouse model of Parkinson's disease (PD) to examine microstructural changes linked to neuroinflammation and neurodegeneration. Methods MPTP (20 mg/kg, i.p.) was given for 4 days, and behavioral assessment, MRI imaging, and immunohistochemistry were performed at 24 h and 72 h after last MPTP treatment. Results At 24 h, DKI showed higher diffusivity metrics in the hippocampus and thalamus, while 1H‐MRS identified reduced Glu/tCr and Glx/tCr ratios in the striatum of MPTP‐treated mice compared to saline‐treated mice. Behavioral tests at 72 h revealed motor impairment and DKI showed increased diffusivity in the somatosensory cortex, thalamus, and striatum in MPTP‐treated mice. Notably, at 72 h, the hippocampus showed partial recovery in diffusivity, suggesting adaptive changes or partial restoration. Higher diffusivity was observed in the cortex, striatum, and thalamus in MPTP‐treated mice. Furthermore, 1H‐MRS detected a higher Tau/tCr in the striatum, while in the hippocampus, lower Gln/tCr and NAA/tCr and higher Cho/NAA were observed at 72 h in MPTP‐treated mice, indicating persistent neuronal death and membrane deterioration. Immunofluorescence staining at 72 h confirmed these findings, showing a decrease in NeuN+ neurons and an increase in GFAP+ glial cells in the striatum and hippocampus, indicating neurodegeneration and gliosis. Additionally, MPTP caused a loss of dopaminergic neurons in the substantia nigra and striatum, which likely explains the higher diffusivity shown by DKI. Conclusion These findings demonstrate DKI and 1H‐MRS are sensitive, non‐invasive modalities for detecting and monitoring neurodegenerative microstructural and neurochemical changes, enhancing the understanding of PD‐related pathology and progression. In MPTP‐treated mice, DKI and 1H‐MRS revealed increased hippocampal and thalamic diffusivity with reduced striatal Glu/tCr and Glx/tCr at 24 h. By 72 h, cortical, striatal, and thalamic diffusivity rose, with partial hippocampal recovery. Elevated Tau/tCr and hippocampal metabolite alterations paralleled neuronal loss and gliosis, supporting DKI/1H‐MRS as sensitive biomarkers of progression.

Background Chronic pain and psychiatric comorbidities in juvenile idiopathic arthritis (JIA) persist even during disease remission, suggesting central nervous system (CNS) alterations. This study used proton magnetic resonance spectroscopy ( 1 H-MRS) to investigate neurometabolic changes in the right hippocampus of JIA patients across active and inactive disease phases. Methods A cohort of 248 JIA patients (61 treatment-naïve patients with active JIA and 187 patients with inactive JIA) and 57 healthy controls (HCs) underwent 1 H-MRS of the right hippocampus. Metabolite ratios of total N-acetylaspartate (tNAA), total choline (tCho), myo-inositol (mI), glutamate (Glu), and glutamate-glutamine complex (Glx) relative to total creatine (tCr) were quantified. Associations with systemic inflammation (ESR and CRP) and clinical indices (JADAS-27 and CHAQ) were evaluated. Results Compared with HCs, both JIA groups showed elevated mI/tCr and reduced Glu/tCr and Glx/tCr in the inactive JIA group (all, P  < 0.05). mI/tCr was positively correlated with ESR (rho = 0.269) and CRP (rho = 0.287) in active JIA patients. However, the results did not survive the rigid multiple correction. Notably, tNAA/tCr, tCho/tCr, Glu/tCr and Glx/tCr showed no significant correlations with systemic inflammation and clinical indices for treatment-naïve and inactive JIA patients. Conclusions Sustained hippocampal neuroinflammation (indicated by elevated mI/tCr) and the subsequent glutamatergic synaptic dysfunction (indicated by reduced Glu/tCr and Glx/tCr) were identified in JIA patients. Peripheral inflammation may drive microglial activation during active disease, highlighting the hippocampus as a vulnerable CNS target in chronic inflammatory states.

Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression. The present study utilized anhedonic rats from the unpredictable CMS model of depression to study metabolic recovery in the ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and PFC. The study employed 1H MR spectroscopy (1H MRS) and in-vivo diffusion MRI (d-MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS) and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of week 18 and week 22 in the control group. The d-MRI data have provided an array of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT, WL and WT). CMS exposure induced a significant metabolic alteration in vHP, and significant microstructural alterations were observed in the HP, AM, and PFC in comparison to the age match control and within the anhedonic group. A significantly high level of N-acetylaspartate (NAA) was observed in vHP at the age of week 18 in comparison to age match control and week 20 and week 25 of the anhedonic group. HP and AM showed significant microstructural alterations up to the age of week 22 in the anhedonic group. PFC showed significant microstructural alterations only at the age of week 18, however, most of the metrics showed significantly higher value at the age of week 20 in the anhedonic group. The significantly increased NAA concentration may indicate impaired catabolism due to astrogliosis or oxidative stress. The significantly increased WL in the AM and HP may indicate hypertrophy of AM and reduced volume of HP. Such metabolic and microstructural alterations could be useful in disease diagnosis and follow-up treatment intervention in depression and similar disorders.

Background Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1 H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. Methods We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton’s tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1 H MRS. Results Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. Conclusions Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.

Natural or synthetic scaffolds are essential for developing three-dimensional (3D) cell culture models, as they provide structural stability and accurately replicate the cellular microenvironment. When integrated into optimized setups, scaffold-supported cellular aggregates, such as spheroids, can be non-destructively characterized and monitored using 3T Magnetic Resonance Imaging (MRI). However, a significant technical limitation is the presence of MR artifacts generated by scaffolds, which can severely obscure the visualization of the embedded spheroids. This study systematically evaluated the suitability of various scaffolds and matrices (including Matrigel®, fibrin glue, and several hydrogels) for MRI and MR spectroscopy (MRS). The materials were investigated both native and seeded with chondrosarcoma cells (SW1353). Our findings revealed considerable variability in MR compatibility across different materials. Specifically, fibrin glue proved unsuitable for MR applications due to substantial artifact generation that interfered with the visualization of cellular components. Furthermore, the results emphasize the importance of the observation period, as material degradation processes can introduce confounding factors in longitudinal MR studies. The choice of scaffold material is paramount for the successful analysis of 3D cell models via MRI. Careful selection is required, as the materials’ properties and temporal stability directly impact the interpretability of the acquired data.

Purpose We compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods The predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3 − 6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory. Results The predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62–0.84), total N -acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68 − 0.88)), or NSE at 72 h (0.85 (0.76 − 0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80–0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85–0.98) vs 0.98 (0.96–1.00), p  = 0.037). Conclusion None of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use. Trial registration ClinicalTrials.gov NCT00879892, April 13, 2009.

Background The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown. This study utilized chemical exchange saturation transfer (CEST) imaging combined with proton magnetic resonance spectroscopy ( 1 H-MRS) to monitor the dynamic changes of Glu and GABA in riluzole-treated AD mice, aiming to evaluate the efficacy and mechanism of riluzole in AD treatment. Methods GluCEST, GABACEST and 1 H-MRS were used to longitudinally monitor Glu and GABA levels in 3xTg AD mice treated with riluzole (12.5 mg/kg/day) or vehicle for 20 weeks. Magnetic resonance measurements were performed at baseline, 6, 12, and 20 weeks post-treatment. Cognitive performance was assessed using the Morris Water Maze (MWM) at baseline, 10, and 20 weeks. At the study endpoint, immunohistochemistry, Nissl staining, and Western blot were used to evaluate the brain pathology, neuronal survival, and protein expression. Results GluCEST, GABACEST and 1 H-MRS consistently revealed higher levels of Glu and GABA in the brain of riluzole-treated AD mice compared to untreated controls, which were associated with improvements in spatial learning and memory. The cognitive improvements significantly correlated with the increased GluCEST signals and Glu levels. Immunohistochemistry and Nissl staining demonstrated that riluzole treatment reduced amyloid-beta (Aβ) deposition, tau hyperphosphorylation, GFAP-positive astrocyte activation, and prevented neuronal loss. Moreover, riluzole upregulated the expression of excitatory amino acid transporter 2 (EAAT2), glutamic acid decarboxylase 65/67 (GAD65/67), and glutamine synthetase (GS), suggesting enhanced neurotransmitter metabolism. Conclusions CEST imaging combined with 1 H-MRS demonstrated the effectiveness of riluzole in modulating Glu- and GABA-related changes and improving cognitive function in 3xTg AD mice, potentially through regulating key proteins involved in neurotransmitter metabolism. These findings suggest riluzole as a therapeutic agent for Alzheimer’s disease and highlight the utility of multimodal MR imaging in monitoring treatment response and exploring disease mechanisms.