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Proton (1H) Magnetic Resonance Spectroscopy (MRS) is a non-invasive tool capable of quantifying brain metabolite concentrations in vivo. Prioritization of standardization and accessibility in the field has led to the development of universal pulse sequences, methodological consensus recommendations, and the development of open-source analysis software packages. One on-going challenge is methodological validation with ground-truth data. As ground-truths are rarely available for in vivo measurements, data simulations have become an important tool. The diverse literature of metabolite measurements has made it challenging to define ranges to be used within simulations. Especially for the development of deep learning and machine learning algorithms, simulations must be able to produce accurate spectra capturing all the nuances of in vivo data. Therefore, we sought to determine the physiological ranges and relaxation rates of brain metabolites which can be used both in data simulations and as reference estimates. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we've identified relevant MRS research articles and created an open-source database containing methods, results, and other article information as a resource. Using this database, expectation values and ranges for metabolite concentrations and T2 relaxation times are established based upon a meta-analyses of healthy and diseased brains.

Carnosine, an MR‐visible dipeptide in human muscle, is well characterized by two peaks at ~8 and ~7 ppm from C2 and C4 imidazole protons. Like creatine and other metabolites, carnosine is subject to residual dipolar coupling in the anisotropic environment of muscle fibers, but the effects have not been studied extensively. Single‐voxel TE 30–32 PRESS spectra from three different 3T studies were acquired from gastrocnemius medialis and soleus muscles in the human lower leg. In these studies, carnosine T2 values were measured, and spectra were obtained at three different foot angles. LCModel was used to fit the carnosine peaks with a basis set that was generated using shaped RF pulses and included a range of dipolar couplings affecting the C4 peak. A seven‐parameter analytic expression was used to fit the CH2 doublets of creatine. It incorporated an optimized "effective TE" value to model the effect of shaped RF pulses. The fits confirm that the triplet C4 peak of carnosine is dipolar coupled to a pair of CH2 protons, with no need to include a contribution from a separate pool of freely rotating uncoupled carnosine. Moreover, the couplings experienced by carnosine C4 protons and creatine CH2 protons are strongly correlated (R2 = 0.88, P<0.001), exhibiting a similar 3cos2θ − 1 dependence on the angle θ between fiber orientation and B0. T2 values for the singlet C2 peak of gastrocnemius carnosine are inversely proportional to the C4 dipolar coupling strength (R2 = 0.97, P < 0.001), which in turn is a function of foot orientation. This dependence indicates that careful positioning of the foot while acquiring lower leg muscle spectra is important to obtain reproducible carnosine concentrations. As proton magnetic resonance spectroscopy of carnosine is currently used to non‐invasively estimate the muscle fiber typology, these results have important implications in sport science. [ABSTRACT FROM AUTHOR]

Introduction We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Material and methods A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.

Introduction: We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods: A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results: The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions: We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens. [ABSTRACT FROM AUTHOR]

Purpose: To develop a Bayesian convolutional neural network (BCNN) with Monte Carlo dropout sampling for metabolite quantification with simultaneous uncertainty estimation in deep learning–based proton MRS of the brain. Methods: Human brain spectra were simulated using basis spectra for 17 metabolites and macromolecules (N = 100 000) at 3.0 Tesla. In addition, actual in vivo spectra (N = 5) were modified by adjusting SNR and linewidth with increasing severity of spectral degradation (N = 50). A BCNN was trained on the simulated spectra to generate a noise‐free, line‐narrowed, macromolecule signal‐removed, metabolite‐only spectrum from a typical human brain spectrum. At inference, each input spectrum was Monte Carlo dropout sampled (50 times), and the resulting mean spectrum and variance spectrum were used for metabolite quantification and uncertainty estimation, respectively. Results: Using the simulated spectra, the mean absolute percent errors of the BCNN‐predicted metabolite content were < 10% for Cr, Glu, Gln, mI, NAA, and Tau (< 5% for Glu, NAA, and mI). For all metabolites, the correlations (r's) between the ground‐truth error and BCNN‐predicted uncertainty ranged 0.72–0.94 (0.83 ± 0.06; p < 0.001). Using the modified in vivo spectra, the extent of variation in the estimated metabolite content against the increasing severity of spectral degradation tended to be smaller with BCNN than with linear combination of model spectra (LCModel). Overall, the variation in metabolite content tended to be more highly correlated with the uncertainty from BCNN than with the Cramér‐Rao lower‐bounds from LCModel (0.938 ± 0.019 vs. 0.881 ± 0.057 [p = 0.115]). Conclusion: The BCNN with Monte Carlo dropout sampling may be used in deep learning–based MRS for the estimation of uncertainty in the machine‐predicted metabolite content, which is important in the clinical application of deep learning–based MRS. [ABSTRACT FROM AUTHOR]

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease‐modifying therapies. Proton MRS (1H‐MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ‐aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1H‐MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N‐acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing‐remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross‐sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (F2,65 = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine (F2,65 = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA (F2,65 = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione (F2,65 = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p < 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (ρ = −0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing‐remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (ρ = −0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing‐remitting multiple sclerosis. [ABSTRACT FROM AUTHOR]

Objective: To determine whether proton magnetic resonance spectroscopy (1H-MRS) can detect neurochemical changes in amyotrophic lateral sclerosis (ALS) associated with heterogeneous functional decline.Methods: Nineteen participants with early-stage ALS and 18 age-matched and sex ratio-matched controls underwent ultra-high field 1H-MRS scans of the upper limb motor cortex and pons, ALS Functional Rating Scale-Revised (ALSFRS-R total, upper limb and bulbar) and upper motor neuron burden assessments in a longitudinal observational study design with follow-up assessments at 6 and 12 months. Slopes of neurochemical levels over time were compared between patient subgroups classified by the rate of upper limb or bulbar functional decline. 1H-MRS and clinical ratings at baseline were assessed for ability to predict study withdrawal due to disease progression.Results: Motor cortex total N-acetylaspartate to myo-inositol ratio (tNAA:mIns) significantly declined in patients who worsened in upper limb function over the follow-up period (n=9, p=0.002). Pons glutamate + glutamine significantly increased in patients who worsened in bulbar function (n=6, p<0.0001). Neurochemical levels did not change in patients with stable function (n=5-6) or in healthy controls (n=14-16) over time. Motor cortex tNAA:mIns and ALSFRS-R at baseline were significantly lower in patients who withdrew from follow-up due to disease progression (n=6) compared with patients who completed the 12-month scan (n=10) (p<0.001 for tNAA:mIns; p<0.01 for ALSFRS-R), with a substantially larger overlap in ALSFRS-R between groups.Conclusion: Neurochemical changes in motor areas of the brain are associated with functional decline in corresponding body regions. 1H-MRS was a better predictor of study withdrawal due to ALS progression than ALSFRS-R. [ABSTRACT FROM AUTHOR]

Proton (1H) Magnetic Resonance Spectroscopy (MRS) is a non-invasive tool capable of quantifying brain metabolite concentrations in vivo. Prioritization of standardization and accessibility in the field has led to the development of universal pulse sequences, methodological consensus recommendations, and the development of open-source analysis software packages. One on-going challenge is methodological validation with ground-truth data. As ground-truths are rarely available for in vivo measurements, data simulations have become an important tool. The diverse literature of metabolite measurements has made it challenging to define ranges to be used within simulations. Especially for the development of deep learning and machine learning algorithms, simulations must be able to produce accurate spectra capturing all the nuances of in vivo data. Therefore, we sought to determine the physiological ranges and relaxation rates of brain metabolites which can be used both in data simulations and as reference estimates. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we've identified relevant MRS research articles and created an open-source database containing methods, results, and other article information as a resource. Using this database, expectation values and ranges for metabolite concentrations and T 2 relaxation times are established based upon a meta-analyses of healthy and diseased brains. [Display omitted] • Database of MRS results is presented to inform simulation and methodological validation. • Meta-analysis of physiological ranges of brain metabolite concentrations in healthy and clinical populations. • Meta-analysis and modeling of metabolite T 2 relaxation time measurements. [ABSTRACT FROM AUTHOR]

Total N-acetyl-aspartate + N-acetyl-aspartate-glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (1H-MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%-65% of the brain. Here we wish to demonstrate that non-localized, whole-head (WH) 1H-MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 ± 8.5 years old, were recruited and underwent T1-weighted MRI for tissue segmentation, non-localizing, approximately 3 min WH 1H-MRS ( TE/ TR/ TI = 5/10/940 ms) and 30 min 1H-MR spectroscopic imaging (MRSI) ( TE /TR = 35/2100 ms) in a 360 cm3 volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 ± 0.5, 5.5 ± 0.4 and 1.3 ± 0.2 mM, were all within 10% of the WH: 8.6 ± 1.1, 6.0 ± 1.0 and 1.3 ± 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the 'brain-only' VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 ± 0.03 (brain ≈ 30% of WH volume). Air-tissue susceptibility-driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non-localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH-1H-MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders. [ABSTRACT FROM AUTHOR]

Friedreich's ataxia (FRDA) is the commonest autosomal recessive ataxia, caused by GAA triplet expansion in the frataxin gene. Neuropathological studies in FRDA demonstrate that besides the primary neurodegeneration of the dorsal root ganglia, there is a progressive atrophy of the cerebellar dentate nucleus. Diffusion-weighted imaging (DWI) detected microstructural alterations in the cerebellum of FRDA patients. To investigate the biochemical basis of these alterations, we used both DWI and proton MR spectroscopy (H-MRS) to study the same cerebellar volume of interest (VOI) including the dentate nucleus. DWI and H-MRS study of the left cerebellar hemisphere was performed in 28 genetically proven FRDA patients and 35 healthy controls. In FRDA mean diffusivity (MD) values were calculated for the same H-MRS VOI. Clinical severity was evaluated using the International Cooperative Ataxia Rating Scale (ICARS). FRDA patients showed a significant reduction of N-acetyl-aspartate (NAA), a neuroaxonal marker, and choline (Cho), a membrane marker, both expressed relatively to creatine (Cr), and increased MD values. In FRDA patients NAA/Cr negatively correlated with MD values ( r = −0.396, p = 0.037) and with ICARS score ( r = −0.669, p < 0.001). Age-normalized NAA/Cr loss correlated with the GAA expansion ( r = −0.492, p = 0.008). The reduced cerebellar NAA/Cr in FRDA suggests that neuroaxonal loss is related to the microstructural changes determining higher MD values. The correlation between NAA/Cr and the severity of disability suggests that this biochemical in vivo MR parameter might be a useful biomarker to evaluate therapeutic interventions. [ABSTRACT FROM AUTHOR]

MRS enables insight into the chemical composition of central nervous system tissue. However, technical challenges degrade the data quality when applied to the human spinal cord. Therefore, to date detection of only the most prominent metabolite resonances has been reported in the healthy human spinal cord. The aim of this investigation is to provide an extended metabolic profile including neurotransmitters and antioxidants in addition to metabolites involved in the energy and membrane metabolism of the human cervical spinal cord in vivo. To achieve this, data quality was improved by using a custom-made, cervical detector array together with constructive averaging of a high number of echo signals, which is enabled by the metabolite cycling technique at 3T. In addition, the improved spinal cord spectra were extensively cross-validated, in vivo, post-mortem in situ and ex vivo. Reliable identification of up to nine metabolites was achieved in group analyses for the first time. Distinct features of the spinal cord neurochemical profile, in comparison with the brain neurotransmission system, include decreased concentrations of the sum of glutamate and glutamate and increased concentrations of aspartate, γ-amino-butyric acid, scyllo-inositol and the sum of myo-inositol and glycine. [ABSTRACT FROM AUTHOR]

Multimodal MRI is the state of the art method for clinical diagnostics and therapy monitoring of the spinal cord, with MRS being an emerging modality that has the potential to detect relevant changes of the spinal cord tissue at an earlier stage and to enhance specificity. Methodological challenges related to the small dimensions and deep location of the human spinal cord inside the human body, field fluctuations due to respiratory motion, susceptibility differences to adjacent tissue such as vertebras and pulsatile flow of the cerebrospinal fluid hinder the clinical application of 1H MRS to the human spinal cord. Complementary to previous studies that partly addressed these problems, this work aims at enhancing the signal-to-noise ratio (SNR) of 1H MRS in the human spinal cord. To this end a flexible tight fit high density receiver array and ultra-high field strength (7 T) were combined. A dielectric waveguide and dipole antenna transmission coil allowed for dual channel RF shimming, focusing the RF field in the spinal cord, and an inner-volume saturated semi-LASER sequence was used for robust localization in the presence of B1+ inhomogeneity. Herein we report the first 7 T spinal cord 1H MR spectra, which were obtained in seven independent measurements of 128 averages each in three healthy volunteers. The spectra exhibit high quality (full width at half maximum 0.09 ppm, SNR 7.6) and absence of artifacts and allow for reliable quantification of N-acetyl aspartate (NAA) (NAA/Cr (creatine) 1.31 ± 0.20; Cramér-Rao lower bound (CRLB) 5), total choline containing compounds (Cho) (Cho/Cr 0.32 ± 0.07; CRLB 7), Cr (CRLB 5) and myo-inositol (mI) (mI/Cr 1.08 ± 0.22; CRLB 6) in 7.5 min in the human cervical spinal cord. Thus metabolic information from the spinal cord can be obtained in clinically feasible scan times at 7 T, and its benefit for clinical decision making in spinal cord disorders will be investigated in the future using the presented methodology. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chanarin–Dorfman Syndrome (CDS) is caused by a defect in the CGI-58/ABHD5 gene resulting in a deficiency of CGI-58 and in intracellular accumulation of triacylglycerol in skin and liver. Patients are mainly characterized by congenital ichthyosis, but the clinical phenotype is very heterogeneous. Distinct brain involvement has never been described. We present a clinical description of two patients with congenital ichthyosis. On suspicion of Sjögren–Larsson syndrome (SLS) single-voxel 1H-MR spectroscopy of the brain was performed and biochemical testing of fatty aldehyde dehydrogenase (FALDH) to establish this diagnosis gave normal results. Vacuolisation in a peripheral blood smear has led to the CDS suspicion. In both patients the diagnosis CDS was confirmed by ABHD5 mutation analysis. Interestingly, a clear lipid accumulation in the cerebral white matter, cortex and basal ganglia was demonstrated in both CDS-patients. These results demonstrate, for the first time, cerebral involvement in CDS and give new insights in the complex phenotype. Since the clinical implications of this abnormal cerebral lipid accumulation are still unknown, further studies are warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Metabolic disturbance is associated with risk for neurodegeneration, and cerebral glucose hypometabolism is prominent in Alzheimer's disease (AD). Ketone metabolism can compensate for glucose hypometabolism and confers other benefits pertinent to neurodegeneration, among them reduction of oxidative stress and AD pathological factors, suggesting its potential as a therapeutic intervention. In a prior controlled trial, we showed that six weeks' carbohydrate restriction induced ketogenesis and produced improvements in metabolic parameters and memory performance in older adults with Mild Cognitive Impairment (MCI). Those benefits were attributed to the correction of hyperinsulinemia and to the presumed enhancement of cerebral bioenergetic function associated with ketone metabolism. OBJECTIVE: To assess the effect of dietary ketosis on cerebral metabolites in older adults with MCI. METHODS: We enrolled a sample of five MCI participants in a ketogenic dietary regimen and performed pre- and post-intervention proton magnetic resonance spectroscopy to investigate changes in neurochemical metabolites. We also assessed cognitive function and metabolic and anthropometric factors. RESULTS: We observed a significant increase in myo-inositol (p = 0.02) and trends for increases in N-acetyl-aspartate (p = 0.09) and creatine + phosphocreatine (p = 0.11) after six weeks on the ketogenic regimen. Working memory (p = 0.01) and long-term memory (p = 0.07) performances also improved. CONCLUSIONS: This study offers novel, preliminary evidence of cerebral bioenergetic enhancement with mild dietary ketosis in aging humans. Further investigation in controlled trials is warranted to assess the preventive and treatment implications of this intervention for age-related memory decline and dementia. [ABSTRACT FROM AUTHOR]

The accuracy of metabolite concentrations measured using in vivo proton (1H) MRS is enhanced following correction for spin-spin ( T2) relaxation effects. In addition, metabolite proton T2 relaxation times provide unique information regarding cellular environment and molecular mobility. Echo-time (TE) averaging 1H MRS involves the collection and averaging of multiple TE steps, which greatly simplifies resulting spectra due to the attenuation of spin-coupled and macromolecule resonances. Given the simplified spectral appearance and inherent metabolite T2 relaxation information, the aim of the present proof-of-concept study was to develop a novel data processing scheme to estimate metabolite T2 relaxation times from TE-averaged 1H MRS data. Spectral simulations are used to validate the proposed TE-averaging methods for estimating methyl proton T2 relaxation times for N-acetyl aspartate, total creatine, and choline-containing compounds. The utility of the technique and its reproducibility are demonstrated using data obtained in vivo from the posterior-occipital cortex of 10 healthy control subjects. Compared with standard methods, distinct advantages of this approach include built-in macromolecule resonance attenuation, in vivo T2 estimates closer to reported values when maximum TE ≈ T2, and the potential for T2 calculation of metabolite resonances otherwise inseparable in standard 1H MRS spectra recorded in vivo. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Although measurements of GABA levels in vivo in the human brain using edited proton magnetic resonance spectroscopy (1H-MRS) have been established for some time, it is has not been established how regional GABA levels vary with age in the normal human brain. In this study, 49 healthy men and 51 healthy women aged between 20 and 76years were recruited and J-difference edited spectra were recorded at 3T to determine the effect of age on GABA levels, and to investigate whether there are regional and gender differences in GABA in mesial frontal and parietal regions. Because the signal detected at 3.02ppm using these experimental parameters is also expected to contain contributions from both macromolecules (MM) and homocarnosine, in this study the signal is labeled GABA+ rather than GABA. Significant negative correlations were observed between age and GABA+ in both regions studied (GABA+/Cr: frontal region, r=−0.68, p<0.001, parietal region, r=−0.54, p<0.001; GABA+/NAA: frontal region, r=−0.58, p<0.001, parietal region, r=−0.49, p<0.001). The decrease in GABA+ with age in the frontal region was more rapid in women than men. Evidence of a measureable decline in GABA is important in considering the neurochemical basis of the cognitive decline that is associated with normal aging. [Copyright &y& Elsevier]

MR spectroscopy allows a noninvasive assessment of metabolic information in healthy and pathological central nervous system. Whereas MR spectroscopy has been extensively applied in the brain, only few spectroscopic studies of the spinal cord (SC) have been performed so far. For mice, due to additional technical challenges, in vivo 1H SC MRS has not yet been reported. In this work, the feasibility of short echo time localized proton magnetic resonance spectroscopy using Point RESolved Spectroscopy sequence for the examination of mouse cervical SC at 11.75 T is presented. Several optimizations were performed to improve the static field homogeneity, to reduce physiological motion effects and lipid contaminations arising from SC surrounding tissues, and to provide a careful metabolic quantification. Satisfactory spectrum quality was obtained. The described protocol allowed reliable quantification of five metabolites in the cervical SC. The mean reproducibility regarding the quantification of tNAA, tCr and tCho was ≥ 80%, > 70% for mI and > 55% for Glu, whereas the intersubject variabilities were ≤ 21%. The application of this protocol to transgenic mouse models in pathological conditions such as SC injury or neurodegenerative diseases may thus provide complementary information to MRI and increase our understanding of such pathologies. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To elucidate the functional characteristics of cortical tubers that might be responsible for epilepsy in tuberous sclerosis complex (TSC), proton magnetic resonance spectroscopy (1H-MRS) and [123I] iomazenil (123I-IMZ) single photon emission computed tomography (SPECT) were performed. Methods: 1H-MRS using a clinical 3-tesla magnetic resonance imager was performed in four children with TSC and 10 age-and sex-matched healthy control subjects. A single voxel was set on the right parietal lobe in control subjects. In patients with TSC, a single voxel was set on the epileptogenic tuber in the parietal or temporal lobe, and another voxel was set on the contralateral normal-appearing brain region. N-Acetylaspartate (NAA), myo-Inositol (mIns) and Glutamate (Glu) were analyzed using a conventional STEAM (Stimulated Echo Acquisition Mode) method. The concentration of gamma-aminobutyric acid (GABA) was quantified using MEGA-Point Resolved Spectroscopy (PRESS). Interictal 123I-IMZ SPECT was examined in all four patients with TSC. Results: A significant decrease in the NAA concentration and significant increases in the mIns and GABA concentrations were detected in the cortical tubers of all 4 patients. No significant difference was observed in Glu concentrations. In all of the cortical tubers detected by magnetic resonance imaging, 123I-IMZ binding was significantly decreased. Conclusion: Epileptogenesis in TSC might be caused by decreased inhibition secondary to the decrease in GABA receptors in dysplastic neurons of cortical tubers. An increase in the GABA concentration may compensate for decreased inhibition. [Copyright &y& Elsevier]

Abstract: With 90% of neuroscience clinical trials failing to see efficacy, there is a clear need for the development of disease biomarkers that can improve the ability to predict human Alzheimer''s disease (AD) trial outcomes from animal studies. Several lines of evidence, including genetic susceptibility and disease studies, suggest the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) as a potential biomarker with congruency between humans and animal models. For example, early in AD, patients present with decreased glucose metabolism in the entorhinal cortex and several regions of the brain associated with disease pathology and cognitive decline. While several of the commonly used AD mouse models fail to show all the hallmarks of the disease or the limbic to cortical trajectory, there has not been a systematic evaluation of imaging-derived biomarkers across animal models of AD, contrary to what has been achieved in recent years in the Alzheimer''s Disease Neuroimaging Initiative (ADNI) (). If animal AD models were found to mimic endpoints that correlate with the disease onset, progression, and relapse, then the identification of such markers in animal models could afford the field a translational tool to help bridge the preclinical-clinical gap. Using a combination of FDG-PET and functional magnetic resonance imaging (fMRI), we examined the Tg2576 mouse for global and regional measures of brain glucose metabolism at 7 and 19 months of age. In experiment 1 we observed that at younger ages, when some plaque burden and cognitive deficits have been reported, Tg2576 mice showed hypermetabolism as assessed with FDG-PET. This hypermetabolism decreased with age to levels similar to wild type (WT) counterparts such that the 19-month-old transgenic (Tg) mice did not differ from age matched WTs. In experiment 2, using cerebral blood volume (CBV) fMRI, we demonstrated that the hypermetabolism observed in Tg mice at 7 months could not be explained by changes in hemodynamic parameters as no differences were observed when compared with WTs. Taken together, these data identify brain hypermetabolism in Tg2576 mice which cannot be accounted for by changes in vascular compliance. Instead, the hypermetabolism may reflect a neuronal compensatory mechanism. Our data are discussed in the context of disease biomarker identification and target validation, suggesting little or no utility for translational based studies using Tg2576 mice. [Copyright &y& Elsevier]

Magnetic Resonance Spectroscopy (MRS) is a unique technique that can directly assess the concentration of various biochemical metabolites in the brain. Thus, it is used in the study of molecular pathophysiology of different neuropsychiatric disorders, such as, the major depressive disorder and has been an area of active research. We conducted a computerbased literature search using the Pubmed database with 'magnetic resonance spectroscopy', 'MRS', 'depression', and 'major depressive disorder' as the key words, supplemented by a manual search of bibliographic cross-referencing. Studies in depression report abnormalities in the frontal cortex, basal ganglia, hippocampus, anterior cingulate cortex, and the occipital cortex. These abnormalities improve after treatment with selective serotonin reuptake inhibitor, electroconvulsive therapy, and yoga, and thus, are possibly state-dependent. The findings are consistent with other morphometric and clinical studies and support the proposed pathophysiological theory of dysfunction in the neuronal circuits involving the frontal cortex, limbic cortex, and basal ganglia. Spectroscopy also has potential implications in predicting the response to treatment and formulating individualized pharmacotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Both MRI with FLAIR and T2, diffusion and post-contrast T1 imaging, as well as proton MRS, allow for defining an approach to evaluating MRI and MRS in neurometabolic diseases producing seizures. Examples of this approach are given here in a limited number of cases, recognizing that a more comprehensive review is beyond the scope of this paper. [Copyright &y& Elsevier]

Introduction: Chronic methamphetamine use results in persistent neuropsychological deficits in abstinent methamphetamine dependent (AMD) subjects. We examined the hypothesis that elevated concentration of cerebral glutamate (Glu), an excitatory neurotransmitter and neurotoxin, occurs in human AMD. Materials and Methods: We examined 40 subjects, 18 of whom were AMD, abstinent more than 3 weeks and 22 were age matched controls. A Structured Clinical Interview was applied to exclude AMD with comorbid depression. We used TE-Averaged technique of MRS to uniquely identify and quantify the glutamate resonance at 2.35 ppm on a 3T clinical MR scanner. Statistics, including Bonferroni correction for multiple MRS variables were applied. Results: Glu was significantly higher in frontal white matter of AMD (+19%, P = 0.01) and N-acetylaspartate (NAA), an axonal marker, was lower (-14%, P = 0.004). No significant MRS abnormalities were detected in posterior gray matter. Significant correlations were observed between NAA and Glu (P = 0.002 for AMD and P = 0.06 for controls in the posterior gray matter and P = 0.01 for controls and not significant for AMD in the frontal white matter). Conclusion: Our results demonstrate a significant excess of glutamate in frontal white matter of AMD subjects and offer support for the hypothesis that methamphetamine abuse may exert its long-term neuro-toxicity via glutamate. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to estimate the gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) concentrations in the cortical tubers of patients with tuberous sclerosis complex (TSC) using the MEGA-editing J-difference method and a stimulated echo-acquisition mode with a short echo time, and to determine which abnormality was more dominant between GABA and Glx in patients with TSC with epilepsy. This study included six patients with TSC (mean age, 4.3 years) and seven control subjects (mean age, 4.8 years). Measurements were obtained with a three-Tesla apparatus and postprocessing was conducted with an LCModel. The GABA level in the cortical gray matter (cgGABA) was calculated as a result of segmentation in voxels and from the literature values for gray and white matter ratios for GABA. Increased GABA and myo-inositol (mI) concentrations and a decreased N-acetyl aspartate (NAA) concentration were observed in the cortical tubers. The cgGABA level, and cgGABA/NAA and cgGABA/Glx ratios were also higher in patients with TSC than in control subjects. No significant difference was found in Glx concentration between patients with TSC and control subjects. Although the number of patients with TSC in this study was small, the increase in GABA and no significant change in Glx were consistent with previous neurochemical studies and support the hypothesis that brain GABA plays a key role in the pathophysiology of epilepsy during the process of neuronal development. [Copyright &y& Elsevier]

Abstract: Objectives: Sixty three healthy subjects were measured to assess dependence of brain metabolites on age using short- and long echo time spectroscopy in different brain regions. Material and methods: Younger and elderly humans were measured with long echo time (TE=135ms) 3D-MR-spectroscopic imaging (MRSI) (10 subjects) and with ultra-short echo (TE=11ms) time 2D-MRSI (7 subjects). In addition, results from single voxel 1H-spectroscopy (TE=20ms) of two cohorts of 46 healthy subjects were retrospectively correlated with age. Results: 3D-MR SI revealed reduced NAA/Cr in the older group in the frontal lobe (−22%; p <0.01), parietal lobe (−28%; p <0.01) and semiovale (−9%; p <0.01) compared to the younger group. Cho/Cr was elevated in the semiovale (+35%; p <0.01) and in the n. lentiformis (+42%; p <0.01) in the older group. NAA/Cho was reduced in all regions measured, except the thalamus, in the older group compared to the younger group (from −21 to −49%; p <0.01). 2D-MRSI revealed decreased total NAA (−3.1% per decade; p <0.01) and NAA/Cr (−3.8% per decade; p <0.01), increased total Cho (+3.6% per decade; p <0.01) and Cho/Cr (+4.6% per decade; p <0.01) and increased total myo-Inositol (mI, +4.7% per decade; p <0.01) and mI/Cr (+5.4% per decade; p <0.01) and decreased NAA/Cho (−8% per decade; p <0.01) in semiovale WM. Results from single voxel spectroscopy revealed a significantly negative correlation of NAA/Cho in frontal (−13% per decade; p <0.01) and in temporal lobe (−7.4% per decade; p <0.01) as well as increased total Cr (10% per decade; p <0.01) in frontal lobe. Other results from single voxel measurements were not significant, but trends were comparable to that from multivoxel spectroscopy. Conclusion: Age-related changes measured with long echo time and short echo time 1H-MRS were comparable and cannot, therefore, be caused by different T2 relaxation times in young and old subjects, as suggested previously. [Copyright &y& Elsevier]

Abstract: Proton magnetic resonance spectroscopy was performed at 3 T using the echo time-averaged point-resolved spectroscopy method to determine the effects of age, gender and brain region on glutamate (Glu) concentrations in the healthy human brain. Thirty healthy men and 20 healthy women aged between 21 and 71 years were studied. Significant regional variations of Glu concentrations were observed. Glu concentration in the gray matter (GM) was approximately 25% higher than that in the white matter. Significant age-dependent decreases in Glu concentrations were observed in the basal ganglia (r=−0.75, P<.001) and parietal GM (r=−0.66, P<.001) of men but not those of women. Our findings demonstrate regional variations of Glu concentrations and suggest that the male brain may be more vulnerable to aging than the female brain. Our results also highlight the importance of brain region, age and gender matching in clinical studies. [Copyright &y& Elsevier]

Abstract: Proton magnetic resonance spectroscopy (1H MRS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) provide functional information, including vascular volume, vascular permeability and choline (Cho) metabolism. In this study, we applied these two imaging modalities to quantitatively characterize 36 malignant breast lesions in 32 patients and analyzed the correlation between them. Cho concentration was quantified by single-voxel 1H MRS using water as an internal reference. The measured Cho levels ranged from 0.32 to 10.47 mmol/kg, consistent with previously reported values. In 25 mass-type lesions, the Cho concentration was significantly correlated with tumor size (r=.69, P<.0002). In addition, the Cho level was found to be significantly higher in lesions presenting as mass-type lesions compared to non-mass-type diffuse enhancements (P=.035). The enhancement kinetics from tissues covered within each MRS voxel were measured and analyzed with a two-compartmental model to obtain pharmacokinetic parameters K trans and k ep. A significant correlation was found between the Cho level and the pharmacokinetic parameter k ep (r=.62, P<.0001), indicating that tissues with a high Cho level have higher wash-out rates in DCE MRI. The results suggest a correlation between Cho metabolism and angiogenesis activity, which might be explained by the association of Cho with cell replication and angiogenesis required to support tumor growth. [Copyright &y& Elsevier]

BACKGROUND: Exposure to lead is known to have adverse effects on cognition in several different populations. Little is known about the underlying structural and functional correlates of such exposure in humans. OBJECTIVES: We assessed the association between cumulative exposure to lead and levels of different brain metabolite ratios in vivo using magnetic resonance spectroscopy (MRS). METHODS: We performed MRS on 15 men selected from the lowest quintile of patella bone lead within the Department of Veterans Affairs' Normative Aging Study (NAS) and 16 from the highest to assess in the hippocampal levels of the metabolites N-acetylaspartate, myoinositol, and choline, each expressed as a ratio with creatine. Bone lead concentrations--indicators of cumulative lead exposure--were previously measured using K-X-ray fluorescence spectroscopy. MRS was performed on the men from 2002 to 2004. RESULTS: A 20-µg/g bone and 15-µg/g bone higher patella and tibia bone lead concentration--the respective interquartile ranges within the whole NAS--were associated with a 0.04 [95% confidence interval (CI), 0.00-0.08; p = 0.04] and 0.04 (95% CI, 0.00-0.08; p = 0.07) higher myoinositol- to-creatine ratio in the hippocampus. After accounting for patella bone lead declines over time, analyses adjusted for age showed that the effect of a 20-µg/g bone higher patella bone lead level doubled (0.09; 95% CI, 0.01-0.17; p = 0.03). CONCLUSIONS: Cumulative lead exposure is associated with an increase in the myinositol-to-creatine ratio. These data suggest that, as assessed with MRS, glial effects may be more sensitive than neuronal effects as an indicator of cumulative exposure to lead in adults. [ABSTRACT FROM AUTHOR]

Spectroscopic imaging can be helpful for the noninvasive identification of parenchymal brain tumors. The objective of the present study was the characterization of the metabolic profile of intracranial metastases, based on proton magnetic resonance spectroscopy (MRS). One hundred and four metastatic brain tumors were evaluated by long-echo (TR, 2000 ms; TE, 136 ms) single-voxel volume-selected proton MRS. In 83 patients the tumor fraction within the MRS voxel constituted more than 50%. Compared to normal brain, the tumors showed statistically significant decreases of N-acetylaspartate ( P < 0.0001), creatine ( P < 0.0001), and the [NAA]/choline-containing compounds ratio ( P < 0.0001), increases of [Cho] ( P < 0.0001) and the mobile lipids/[Cr] ratio ( P < 0.0001) and the lactate/[Cr] ratio ( P < 0.05), and the more frequent presence of [Lip] ( P < 0.0001) and [Lac] ( P < 0.0001) resonances. However, the majority of these differences were lost when data for patients whose tumor fraction within the MRS voxel constituted less than 50% were analyzed separately. Determination of the predominant metabolite peak on the MR spectrum [NAA, Cho, Lip] permitted us to define three general metabolic patterns of brain metastases, which, showed statistically significant associations with the size of the neoplasm ( P < 0.001), type of its contrast enhancement ( P < 0.01), and the extent of perilesional edema ( P < 0.05). Proton MRS can define metabolically different subsets of metastatic brain tumors, and these characteristics should be taken into consideration during the differential diagnosis of parenchymal brain lesions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether improvements in signal‐to‐noise ratio (SNR) and spectral resolution are found in spectra from patients with brain metastases obtained at higher magnetic field strengths using standard clinical instrumentation. Material and Methods: Six patients with brain metastases, 13 healthy volunteers, and a phantom containing brain metabolites were examined using two clinical MR instruments operating at 1.5T (Siemens) and 3T (Philips) with standard clinical head coils. Spectra were obtained using a point resolved spectroscopy pulse sequence, echo times (TE) 32 ms and 144 ms, and repetition time 2000 ms from a volume‐of‐interest (VOI) of size 15×15×15 mm 3 . SNR and spectral resolution of the metabolites N‐acetylaspartate, choline, and creatine compounds in spectra from 3T were compared to the 1.5T spectra. Results: In general, spectral resolution was improved by 25–30% at higher magnetic field strength. Only minor improvements in SNR were obtained at 3T using short echo time and 20–50% at long echo time. Conclusion: SNR and spectral resolution were improved at higher magnetic field strength, especially with TE 144 ms, including spectra from patients with heterogeneous brain tumors. However, differences in the defined effective VOI, particularly at short echo time, reduced the expected effect of increased magnetic field strength on the measured SNR. [ABSTRACT FROM AUTHOR]

Various types of intracranial metastases exhibit different growth patterns, which can be reflected in their metabolic characteristics and investigated noninvasively by proton magnetic resonance spectroscopy (1H-MRS). The objective of the present study was comparison of the 1H-MRS-detected metabolic parameters in brain metastases of different origin. Twenty-five patients (15 men and 10 women; mean age, 62.0 years) with single, previously nontreated metastatic brain tumors were investigated by long-echo single-voxel volume-selected 1H-MRS. The primary cancer was located in the lungs (10 cases), colon and rectum (8 cases), breast (3 cases), kidney (2 cases), prostate (1 case), and cardiac muscle (1 case). Comparison of clinical and radiological variables, including type of tumor contrast enhancement and extension of peritumoral edema, did not disclose statistically significant differences in metastatic brain tumors of different origin. At the same time, comparison of 1H-MRS-detected metabolic characteristics revealed that metastases of colorectal carcinoma have greater content of mobile lipids (Lip) compared to other neoplasms. In conclusion, high Lip content in the viable brain metastases of colorectal carcinoma can be used as an additional diagnostic clue for noninvasive identification of these tumors and should be taken into consideration in cases of 1H-MRS-based differentiation of their recurrence and radiation-induced necrosis after radiosurgical or radiotherapeutic treatment. [ABSTRACT FROM AUTHOR]

Multivoxel proton magnetic resonance spectroscopy (MRS) was used for differentiation of radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for intracranial metastases in 33 consecutive cases. All patients presented with enlargement of the treated lesion, increase of perilesional brain edema, and aggravation or appearance of neurological signs and symptoms on average 9.3 ± 4.9 months after primary treatment. Metabolic imaging defined four types of lesions: pure tumor recurrence (11 cases), partial tumor recurrence (11 cases), radiation-induced tumor necrosis (10 cases), and radiation-induced necrosis of the peritumoral brain (1 case). In 1 patient, radiation-induced tumor necrosis was diagnosed 9 months after radiosurgery; however, partial tumor recurrence was identified 6 months later. With the exception of midline shift, which was found to be more typical for radiation-induced necrosis ( P < 0.01), no one clinical, radiologic, or radiosurgical parameter either at the time of primary treatment or at the time of deterioration showed a statistically significant association with the type of the lesion. Proton MRS-based diagnosis was confirmed histologically in all surgically treated patients (7 cases) and corresponded well to the clinical course in others. In conclusion, multivoxel proton MRS is an effective diagnostic modality for identification of radiation-induced necrosis and tumor recurrence that can be used for monitoring of metabolic changes in intracranial neoplasms after radiosurgical treatment. It can be also helpful for differentiation of radiation-induced necrosis of the tumor and that of the peritumoral brain, which may have important clinical and medicolegal implications. [ABSTRACT FROM AUTHOR]

Magnetic resonance (MR) techniques have revolutionized the assessment of brain development and injury in the newborn. MR studies at 3 T or above are becoming widespread; however, given the high cost and complexity of high-field MR systems, it is important to assess their benefits and limitations for clinical practice. MR spectroscopy (MRS) studies at high field carry potential benefits such as improved signal-to-noise ratio (SNR) and chemical shift dispersion compared with 1.5 T. However, safety is a very important consideration as radiofrequency (RF) tissue heating and acoustic noise also increase with field strength. Furthermore, increased chemical-shift dependence of the position of the volume of interest (VOI), shorter transverse and longer longitudinal relaxation times constitute additional challenges. We describe the first in-vivo, proton MRS studies of newborn human brain at 4.7 T. Nine infants with neonatal encephalopathy, all ventilated and with continuous physiological monitoring, were studied. We used L-FOCI localization, mostly with a VOI centred on the thalami. The absence of 4.7 T results from healthy infants made it impossible to interpret pathological metabolite peak-area ratios. However, concentration ratios and concentrations should be field-strength independent and interpretable using control values acquired at lower field. Of eight infants with concentration-ratio measurements, seven had low [ N-acetylaspartate (NAA)]/[choline (Cho)] and three increased [lactate]/[NAA]. Of the two infants with ‘concentration’ measurements both had low [NAA] and one reduced [creatine]. We used an adult coil and consequent RF power restrictions had repercussions for the minimum magnetization recovery time (TR). A smaller, neonatal coil should improve SNR and, with less RF power, relax TR constraints thereby enabling fuller exploitation of the potential of high-field MRS. [ABSTRACT FROM AUTHOR]

Abstract: Long-echo (TR: 2000 ms, TE: 136 ms) proton MRS of the cerebral tissue in the vicinity to intracranial lesion was done in 15 patients, mainly with parenchymal brain tumors. Significant decrease of N-acetylaspartate (NAA) (P&#60;0.001) and more frequent presence of lactate (P&#60;0.01) comparing with distant normal white matter were found in the perilesional brain tissue. The level of NAA in the perilesional brain tissue had negative associations with presence of lactate in the lesion (P&#60;0.05), excess of lactate in the lesion compared to perilesional brain (P&#60;0.01), grade of the perilesional edema (P&#60;0.01) and patient''s age (P&#60;0.05). Multivariate analysis disclosed that identification of lactate in the lesion is associated with lower relative NAA content in the perilesional brain tissue, independently on the presence or absence of any other factor, including brain edema (P&#60;0.001). In patients with lobar lesions who had at least one epileptic seizure during course of their disease the relative NAA content in the perilesional brain was significantly lower, comparing with those who were seizure-free (P&#60;0.05). Therefore, lactate diffused from the tumor, or other metabolites secreted by lactate-producing neoplasm, should be considered as important contributors to the neuronal dysfunction in the surrounding brain. Decrease of NAA in the vicinity to intracranial lesions may reflect neuronal alteration responsible for associated epilepsy. [Copyright &y& Elsevier]

Evaluation of early metabolic changes in metastatic brain tumors after Gamma Knife radiosurgery was performed by long-echo (TR, 2000ms; TE, 136 ms; 128–236 acquisitions) volume-selected single-voxel proton magnetic resonance spectroscopy (MRS). Eighty-five brain metastases in 81 patients were investigated before treatment and 16–18h thereafter. Standard metabolic ratios, namely N-acetylaspartate (NAA)/creatine (Cr), phosphorylcholine/glycerophosphorylcholine (Cho)/Cr, NAA/Cho, lactate (Lac)/Cr, and mobile lipids (Lip)/Cr, were calculated, and comparison of their values before and after irradiation was done. No volumetric changes of any neoplasm were found in any case on the next day after treatment. At the same time, significant reduction of Cho/Cr ( P<0.001) and NAA/Cr ( P<0.01) ratios on the proton MRS of the tumor was disclosed. Reduction of Cho/Cr ratio was significantly more prominent in neoplasms with higher pretreatment Cho/Cr ratios ( P<0.001) and heterogeneous contrast enhancement ( P<0.01). Reduction of NAA/Cr ratio was predominantly determined by its pretreatment value ( P<0.001). The observed decrease of Cho/Cr ratio probably reflects inhibition of proliferative activity and early apoptotic cell loss, whereas reduction of NAA/Cr may result from radiation-induced modulation of neuronal activity in the peritumoral brain tissue. Serial proton MRS represents a valuable diagnostic tool for evaluation of metabolic changes in intracranial neoplasms after radiosurgical treatment. [ABSTRACT FROM AUTHOR]

The pathogenesis of Gulf War Syndrome (GWS) is not clearly understood. Data exist to suggest that GWS may originate from a combination of chronic fatigue and sensitivity to the exposure of exogenous agents. Since the head region of hippocampus is highly vascularized and thus vulnerable to toxic substances in circulation, we postulated that hippocampal impairment occurs in GWS. To test this, single volume localized in vivo proton MR spectroscopy (MRS) studies of the left and right hippocampi of consenting Gulf War veterans (N=15; 10 with GWS, and 5 without GWS) and control Vietnam veterans (N=6) were conducted in accordance with approved human study protocols. The N-acetyl aspartate (NAA) to creatine and choline to creatine ratios were computed from the spectra. The NAA/creatine ratio of the GWS group (N=10) was found to be significantly lower than that of the entire control group (N=11) or the unaffected GW control group (N=5). No laterality differences were observed among any of the three groups. The choline/creatine ratio of the GWS group was not different from that for either control group. To check the existence of any relationship between age and the NAA/creatine ratios, the entire study population was grouped into those below or above the median age (44.3 years). It was found that the NAA/Cre ratio of the younger group (only Gulf War veterans) was significantly lower than that of the older group. The lower NAA/creatine ratio for the GWS group points to the existence of hippocampal dysfunction. [Copyright &y& Elsevier]

Potential interactions between psychostimulant drugs and infection with feline immunodeficiency virus (FIV) on brain metabolism were evaluated. Four groups of cats were studied: control, FIV positive, methamphetamine (MA) exposed, and FIV positive plus MA exposed. Frontal gray matter, frontal white matter, and caudate brain extracts were studied with proton magnetic resonance spectroscopy (1HMRS). In the frontal white matter, FIV-infected cats showed decreases in creatine and choline, while MA-treated cats had elevated gamma-aminobutyric acid (GABA). The decreased glutamate in FIV cats normalized with MA exposure. FIV and MA both affect brain metabolites individually and combined. 1HMRS is useful for evaluating the effects of FIV and drug abuse in the brain. [Copyright &y& Elsevier]

Automation of proton magnetic resonance spectroscopy (MRS) in recent years has made it possible for MRS measurement to be performed in a shorter time than before, and the number of reports of its usefulness for the assessment of glioma malignancy has been increasing in the past several years. We studied the efficacy of proton MRS when used for glioma and conducted clinicopathological examination of glioma. The subjects were 15 patients who had received a pathological diagnosis of glioma at our hospital (6 cases of glioblastoma, 1 case of anaplastic astrocytoma, 4 cases of low-grade astrocytoma, and 4 cases of radiation necrosis); Siemens Magnetom Vision 1.5T was used for the study. Regions of interest (ROIs) were defined as the areas where abnormal signals were found on magnetic resonance imaging (MRI). Areas of primary peaks, such as choline (Cho), N-acetylaspartate (NAA), and lactate (Lac), were measured, and the ratios to normal brain tissue were examined. This study revealed a tendency of increased malignancy of glioma with a decrease in NAA. Some cases also displayed a decrease in Cho with an increase in malignancy. Assessment of malignancy must not be based on a single ROI alone, but several ROIs should be assessed comprehensively. Measurement was difficult when the tumor volume was small. Because diagnosis of very early glioma by MRS seemed difficult, other adjunctive diagnoses may be necessary. Proton MRS is very useful for diagnosis of glioblastoma. [ABSTRACT FROM AUTHOR]

In the last three decades a range of non-invasive biophysical techniques have been developed, of which Magnetic Resonance (MR) has proved to be the most versatile. Its non-invasive and safe nature has made it the most important diagnostic and research tool in clinical medicine. MR Spectroscopy (MRS) is the only technique in clinical medicine that provides non-invasive access to living chemistry in situ. This article focuses mainly on proton MRS in brain and also phosphorus MRS in calf muscle, with particular reference to the pediatric population, the normal spectrum and its use in various disease conditions in the practice of pediatric neurology. Few representative case studies among different disease groups have also been detailed. [ABSTRACT FROM AUTHOR]

Single voxel proton MR spectroscopy (1H-MRS) of the vermis was obtained in two patients with cerebellitis. In the acute phase 1H-MRS revealed low N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) and normal Cho/Cr ratios. Decrease of the concentration of NAA was confirmed by quantitative analysis in one patient. The NAA/Cr and NAA/Cho ratios and NAA concentration were increased in 1H-MRS examinations obtained 10 and 24 months after the acute episode. 1H-MRS demonstrates reversible metabolite changes in cerebellitis. [Copyright &y& Elsevier]

The purpose of this open-label, crossover study was to determine the safety and efficacy of recombinant insulin-like growth factor-I (rhIGF-I) using magnetic resonance imaging (MRI) and clinical measures of disease activity in seven multiple sclerosis (MS) patients. Monthly clinical and MRI examinations were performed during a 24-week baseline and a 24-week treatment period with rhIGF-I. The primary outcome measure was contrast enhancing lesion (CEL) frequency on treatment compared to baseline. Secondary outcome measures included clinical and MRI measures of disease activity including. white matter lesion load (WMLL), magnetization transfer ratio (MTR), TI-Hypointensity volume, cervical spine cross-sectional area and proton magnetic resonance spectroscopic (MRS) imaging for determining regional metabolite ratios. rhIGF-I (Cephalon) was administered at a dose of 50 mg subcutaneously twice a day for 6 months. rhIGF-I was safe and well tolerated with no severe adverse reactions. There was no significant difference between baseline and treatment periods for any MRI or clinical measures of disease activity. Although rhIGF-I did not alter the course of disease in this small cohort of MS patients, the drug was well tolerated. Further studies using rhIGF-I alone or in combination with other therapies may be of value because of the proposed mechanism of action of this growth factor on the oligodendrocyte and remyelination. Multiple Sclerosis (2002)8,24-29 [ABSTRACT FROM PUBLISHER]