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Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies.
Moriguchi, S, Takamiya, A, Noda, Y, Horita, N, Wada, M, Tsugawa, S, Plitman, E, Sano, Y, Tarumi, R, ElSalhy, M, et al
Molecular psychiatry. 2019;(7):952-964
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Abstract
Alterations in glutamatergic neurotransmission are implicated in the pathophysiology of depression, and the glutamatergic system represents a treatment target for depression. To summarize the nature of glutamatergic alterations in patients with depression, we conducted a meta-analysis of proton magnetic resonance (1H-MRS) spectroscopy studies examining levels of glutamate. We used the search terms: depress* AND (MRS OR "magnetic resonance spectroscopy"). The search was performed with MEDLINE, Embase, and PsycINFO. The inclusion criteria were 1H-MRS studies comparing levels of glutamate + glutamine (Glx), glutamate, or glutamine between patients with depression and healthy controls. Standardized mean differences (SMD) were calculated to assess group differences in the levels of glutamatergic neurometabolites. Forty-nine studies met the eligibility criteria, which included 1180 patients and 1066 healthy controls. There were significant decreases in Glx within the medial frontal cortex (SMD = -0.38; 95% CI, -0.69 to -0.07) in patients with depression compared with controls. Subanalyses revealed that there was a significant decrease in Glx in the medial frontal cortex in medicated patients with depression (SMD = -0.50; 95% CI, -0.80 to -0.20), but not in unmedicated patients (SMD = -0.27; 95% CI, -0.76 to 0.21) compared with controls. Overall, decreased levels of glutamatergic metabolites in the medial frontal cortex are linked with the pathophysiology of depression. These findings are in line with the hypothesis that depression may be associated with abnormal glutamatergic neurotransmission.
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Comparison of magnetic resonance spectroscopy and positron emission tomography in detection of tumor recurrence in posttreatment of glioma: A diagnostic meta-analysis.
Wang, X, Hu, X, Xie, P, Li, W, Li, X, Ma, L
Asia-Pacific journal of clinical oncology. 2015;(2):97-105
Abstract
It is important to distinguish between tumor recurrence and treatment effects in posttreatment patients with high-grade gliomas. Several imaging modalities have been reported in differentiating between tumor recurrence and treatment effects. However, there were no consistent conclusions between different studies. We performed a meta-analysis of 23 studies that compared the diagnostic values of fluorine-18-fluorodeoxyglucose ((18)F-FDG) and (11)C-methionine ((11)C-MET) PET (positron emission tomography) or PET/CT (computed tomography) and magnetic resonance spectroscopy (MRS) in predicting tumor recurrence of gliomas. The pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and summary receiver operating characteristic curves of (18)F-FDG and (11)C-MET PET or PET/CT and MRS in detecting tumor recurrence were calculated. In conclusion, MRS is highly sensitive in the detection of tumor recurrence in glioma.(18)F-FDG PET or PET/CT is highly specific in recurrence diagnosis. (11)C-MET does not have noticeable advantage over (18)F-FDG. The current evidence shows no statistical difference between MRS and PET on the accuracy.
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Magnetic Resonance Spectroscopy in Alzheimer's Disease: Systematic Review and Meta-Analysis.
Wang, H, Tan, L, Wang, HF, Liu, Y, Yin, RH, Wang, WY, Chang, XL, Jiang, T, Yu, JT
Journal of Alzheimer's disease : JAD. 2015;(4):1049-70
Abstract
BACKGROUND The application of non-invasive proton magnetic resonance spectroscopy (1H-MRS) could potentially identify changes in cerebral metabolites in the patients with Alzheimer's disease (AD). However, whether these metabolites can serve as biomarkers for the diagnosis of AD remains unclear. OBJECTIVE Using meta-analysis, we aimed to investigate the patterns of cerebral metabolite changes in several cerebral regions that are strongly associated with cognitive decline in AD patients. METHODS Using Hedges' g effect size, a systematic search was performed in PubMed, Cochrane Library, Ovid, Embase, and EBSCO, and 38 studies were integrated into the final meta-analysis. RESULTS According to the observational studies, N-acetyl aspartate (NAA) in AD patients was significantly reduced in the posterior cingulate (PC) (effect size (ES) =-0.924, p < 0.005) and bilateral hippocampus (left hippocampus: ES =-1.329, p < 0.005; right hippocampus: ES =-1.287, p < 0.005). NAA/Cr (creatine) ratio decreased markedly in the PC (ES =-1.052, p < 0.005). Simultaneously, significant elevated myo-inositol (mI)/Cr ratio was found not only in the PC but also in the parietal gray matter. For lack of sufficient data, we failed to elucidate the efficacy of pharmacological interventions with the metabolites changes. CONCLUSION The available data indicates that NAA, mI, and the NAA/Cr ratio might be potential biomarkers of brain dysfunction in AD subjects. Choline (Cho)/Cr and mI/NAA changes might also contribute toward the diagnostic process. Thus, large, well-designed studies correlated with cerebral metabolism are needed to better estimate the cerebral extent of alterations in brain metabolite levels in AD patients.
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Differential diagnosis between malignant and benign breast lesions using single-voxel proton MRS: a meta-analysis.
Cen, D, Xu, L
Journal of cancer research and clinical oncology. 2014;(6):993-1001
Abstract
OBJECTIVES We aim to investigate the diagnostic capability of single-voxel proton MR spectroscopy (MRS) for benign/malignant discrimination of focal breast lesions with a meta-analysis. MATERIALS AND METHODS The meta-analysis included a total of 750 malignant breast lesions and 419 benign breast lesions from eighteen studies. RESULTS The pooled sensitivity and specificity of MRS were 0.71 (95 % CI 0.68-0.74) and 0.85 (95 % CI 0.81-0.88), respectively. The positive likelihood ratio and negative LR were 4.11 (95 % CI 3.11-5.43) and 0.25 (95 % CI 0.17-0.36), respectively. The P value for χ(2) heterogeneity for all pooled estimates was <0.05. From the fitted summary receiver operating characteristics curve, AUC was 0.89 and Q* was 0.84. Asymmetrical in funnel plots indicated there may be publication bias (t = 2.85, P = 0.012). The meta-regression analysis indicated that neither threshold effect nor evaluated covariates that include strength of field, scanning technique (PRESS or STEAM), repetition time, NSA, and pre- or post-contrast agent were the sources of heterogeneity (all P value >0.05). CONCLUSIONS Single-voxel proton MRS was useful for differentiation between malignant and benign breast lesions. However, pooled diagnostic measures might be overestimated. The standardization of the acquisition protocol for MRS across the multicenter trials is recommended.
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Magnetic resonance spectroscopy in mild cognitive impairment: systematic review and meta-analysis.
Tumati, S, Martens, S, Aleman, A
Neuroscience and biobehavioral reviews. 2013;(10 Pt 2):2571-86
Abstract
Research using proton magnetic resonance spectroscopy (MRS) can potentially elucidate metabolite changes representing early degeneration in Mild Cognitive Impairment (MCI), an early stage of dementia. We integrated the published literature using meta-analysis to identify patterns of metabolite changes in MCI. 29 MRS studies (with a total of 607 MCI patients and 862 healthy controls) were classified according to brain regions. Hedges' g was used as effect size in a random effects model. N-Acetyl Aspartate (NAA) measures were consistently reduced in posterior cingulate (PC), hippocampus, and the paratrigonal white matter (PWM). Creatine (Cr) concentration was reduced in the hippocampus and PWM. Choline (Cho) concentration was reduced in the hippocampus while Cho/Cr ratio was raised in the PC. Myo-inositol (mI) concentration was raised in the PC and mI/Cr ratio was raised in the hippocampus. NAA/mI ratio was reduced in the PC. NAA may be the most reliable marker of brain dysfunction in MCI though mI, Cho, and Cr may also contribute towards this.
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Breast lesions: diagnosis by using proton MR spectroscopy at 1.5 and 3.0 T--systematic review and meta-analysis.
Baltzer, PA, Dietzel, M
Radiology. 2013;(3):735-46
Abstract
PURPOSE To perform a systematic review and meta-analysis to estimate the diagnostic performance of breast proton magnetic resonance (MR) spectroscopy in differentiating benign from malignant lesions and to identify variables that influence the accuracy of MR spectroscopy. MATERIALS AND METHODS A comprehensive search of the PubMed database was performed on articles listed until January 6, 2012. The Medical Subject Headings and text words for the terms "breast," "spectroscopy," and "magnetic resonance" were used. Investigations including more than 10 patients at 1.5 T or 3.0 T applying one-dimensional single-voxel MR spectroscopy or spatially resolved MR spectroscopy for differentiation between benign and malignant breast lesions were eligible. A reference standard had to be established either by means of histopathologic examination or imaging follow-up of 12 or more months. Statistical analysis included pooling of diagnostic accuracy, control for data inhomogeneity, and identification of publication bias. RESULTS Nineteen studies were used for general data pooling. The studies included a total of 1183 patients and 1198 lesions (773 malignant, 452 benign). Pooled sensitivity and specificity were 73% (556 of 761; 95% confidence interval [CI]: 64%, 82%) and 88% (386 of 439; 95% CI: 85%, 91%), respectively. The pooled diagnostic odds ratio (DOR) was 34.30 (95% CI: 16.71, 70.43). For breast cancers versus benign lesions, the area under the symmetric summary receiver operating characteristic curve of MR spectroscopy was 0.88, and the Q* index was 0.81. There was evidence of between-studies heterogeneity regarding sensitivity and DOR (P < .0001). No significant influences of higher field strength, postcontrast acquisition, or qualitative versus quantitative MR spectroscopy measurements were identified. Egger testing confirmed significant publication bias in studies including small numbers of patients (P < .0001). CONCLUSION Breast MR spectroscopy shows variable sensitivity and high specificity in the diagnosis of breast lesions, independent from the technical MR spectroscopy approach. Because of significant publication bias, pooled diagnostic measures might be overestimated.
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1H-MRS in autism spectrum disorders: a systematic meta-analysis.
Ipser, JC, Syal, S, Bentley, J, Adnams, CM, Steyn, B, Stein, DJ
Metabolic brain disease. 2012;(3):275-87
Abstract
We conducted a systematic review and meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies comparing autism spectrum disorder (ASD) patients with healthy controls, with the aim of profiling ASD-associated changes in the metabolites N-acetyl-aspartate (NAA) and Creatine (Cr). Meta-regression models of NAA and Cr levels were employed, using data from 20 eligible studies (N = 852), to investigate age-dependent differences in both global brain and region-specific metabolite levels, while controlling for measurement method (Cr-ratio versus absolute concentrations). Decreased NAA concentrations that were specific to children were found for whole-brain grey and white matter. In addition, a significant decrease in NAA was evident across age categories in the parietal cortex, the cerebellum, and the anterior cingulate cortex. Higher levels of Cr were observed for ASD adults than children in global grey matter, with specific increases for adults in the temporal lobe and decreased Cr in the occipital lobe in children. No differences were found for either NAA or Cr in the frontal lobes. These data provide some evidence that ASD is characterized by age-dependent fluctuations in metabolite levels across the whole brain and at the level of specific regions thought to underlie ASD-associated behavioural and affective deficits. Differences in Cr as a function of age and brain region suggests caution in the interpretation of Cr-based ratio measures of metabolites. Despite efforts to control for sources of heterogeneity, considerable variability in metabolite levels was observed in frontal and temporal regions, warranting further investigation.
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The use of proton magnetic resonance spectroscopy in PTSD research--meta-analyses of findings and methodological review.
Karl, A, Werner, A
Neuroscience and biobehavioral reviews. 2010;(1):7-22
Abstract
Different neuroimaging techniques provided evidence for structural and functional brain alterations in posttraumatic stress disorder (PTSD). Due to technical improvements, especially concerning localization techniques and more reliable analysis methods, one technique, proton magnetic resonance spectroscopy ((1)H-MRS), has increasingly become of interest because it allows further insight into metabolic mechanisms that may contribute to these alterations. The aim of this article is, therefore, to review recent studies utilizing (1)H-MRS of the hippocampus and other brain structures in PTSD. Using meta-analytic methods, we attempted to answer the question if PTSD, as compared to different types of control samples, is accompanied by altered neurometabolite ratios and concentrations in the tissue of different brain regions. A second intent was to review methodological aspects to advise on a minimal standard for reliable results with respect to the application of (1)H-MRS in PTSD. Finally, we discussed the implications of the findings with respect to current PTSD models and future research.
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Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis.
Yildiz-Yesiloglu, A, Ankerst, DP
Psychiatry research. 2006;(1):1-25
Abstract
In a review of the current literature, we identified (1)H MRS studies of major depressive disorder (MDD) that examined the metabolites N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), glutamate/glutamine/gamma-aminobutyric acid-GABA (Glx), and creatine (Cr). Separate meta-analyses comparing adult and pediatric MDD patients with healthy controls were performed. For adults, 14 studies with 227 patients/246 controls for NAA, 15 studies with 240 patients/261 controls for Cho, seven studies with 96 patients/104 controls for mI, six studies with 86 patients/109 controls for Glx, and nine studies with 146 patients/173 controls for Cr were identified. There were six studies containing a total of 79 pediatric depressed patients. We performed 15 separate meta-analyses to combine results from studies with similar characteristics. Adult MDD patients had higher Cho/Cr values than controls in the basal ganglia. In contrast, three studies on Glx levels indicated significantly lower Glx levels in the frontal lobe of MDD patients. The review indicated increased Cho/Cr in the basal ganglia in MDD and no alteration of NAA, suggesting an increased membrane turnover in MDD without a neurodegenerative outcome. Lower Glx levels in depressed patients in contrast to a likely hyperglutamatergic state in bipolar disorder may implicate a different pathophysiological ground in MDD.