High-field Magnetic Resonance Spectroscopy Research Articles

Disorder and Sorption Preferences in a Highly Stable Fluoride-Containing Rare-Earth fcu-Type Metal-Organic Framework.

Rare-earth (RE) metal-organic frameworks (MOFs) synthesized in the presence of fluorine-donating modulators or linkers are an important new subset of functional MOFs. However, the exact nature of the REaXb core of the molecular building block (MBB) of the MOF, where X is a μ2or3-bridging group, remains unclear. Investigation of one of the archetypal members of this family with the stable fcu framework topology, Y-fum-fcu-MOF (1), using a combination of experimental techniques, including high-field (20 T) solid-state nuclear magnetic resonance spectroscopy, has determined two sources of framework disorder involving the μ3-X face-capping group of the MBB and the fumarate (fum) linker. The core of the MBB of 1 is shown to contain a mixture of μ3-F- and (OH)- groups with preferential occupation at the crystallographically different face-capping sites that result in different internally lined framework tetrahedral cages. The fum linker is also found to display a disordered arrangement involving bridging- or chelating-bridging bis-bidentate modes over the fum linker positions without influencing the MBB orientation. This linker disorder will, upon activation, result in the creation of Y3+ ions with potentially one or two additional uncoordinated sites possessing differing degrees of Lewis acidity. Crystallographically determined host-guest relationships for simple sorbates demonstrate the favored sorption sites for N2, CO2, and CS2 molecules that reflect the chemical nature of both the framework and the sorbate species with the structural partitioning of the μ3-groups apparent in determining the favored sorption site of CS2. The two types of disorder found within 1 demonstrate the complexity of fluoride-containing RE-MOFs and highlight the possibility to tune this and other frameworks to contain different proportions and segregations of μ3-face-capping groups and degrees of linker disorder for specifically tailored applications.

Chiral distinction between hydroxychloroquine enantiomers in binding to angiotensin-converting enzyme 2, the forward receptor of SARS-CoV-2

Soon after the outset of the Coronavirus Disease 2019 (COVID-19) pandemic (March-April 2020), formulations of the old antimalarial racemic drug hydroxychloroquine (HCQ) sulfate were authorized by the U.S. Food and Drug Administration (FDA) for emergency treatment of hospitalized patients with COVID-19. A call for the chiral switch of HCQ to the single enantiomer (S)-(+)-HCQ for treating the disease followed. The above authorizations were later withdrawn. Angiotensin-converting enzyme 2 (ACE2) has been recognized to be the forward receptor of SARS-CoV-2, the virus responsible for COVID-19. The objective of the present study was to evaluate the chiral distinction in the potential preferential binding of the HCQ enantiomers to ACE2, as a basis for its future drug repurposing, using high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy. Proton selective spin-lattice relaxation rates were measured for selected diagnostic nuclei; in particular, protons belonging to the quinoline ring proved to be the most affected by the presence of the protein, for both (S)-(+)-HCQ and (R)-(−)-HCQ enantiomers. An increase in mono-selective relaxation rates was observed for both enantiomers. A significant difference in the magnitude of the increase was detected for all protons investigated, up to a 5-fold and an 8-fold increase in the case of (R)-(−)-HCQ and (S)-(+)-HCQ, respectively. Furthermore, comparison between the normalized mono-selective relaxation rates of the two HCQ enantiomers in their binary mixtures with ACE2 pointed out a certain preference for the (S)-(+)-HCQ enantiomer over (R)-(−)-HCQ in the interaction with ACE2. The findings form the basis for a future application of the drug repurposing/chiral-switch combination strategy to racemic HCQ in previously reported indications for hydroxychloroquine treatment and in the search for new indications in which ACE2 receptors are involved.

Mechanochemical Synthesis and Study of the Local Structure of NaGaS2 Glass and Glass-Ceramics.

NaGaS2 is a newly discovered compound that has already shown great promise for a variety of applications because of its layered structure and ion exchange properties. In this work, crystalline NaGaS2 has been synthesized by an alternative method to what has been previously published, namely, by mechanochemistry, either by a direct one-step process or by a two-step process. In the one-step process, crystalline NaGaS2 is directly formed by milling sodium sulfide Na2S and gallium(III) sulfide Ga2S3. However, an amorphous material is present in majority together with the crystalline phase. In the two-step process, amorphous NaGaS2 is first obtained by mechanical milling and then heated above its glass transition temperature to obtain a glass-ceramic mainly composed of crystalline NaGaS2. For the two-step process, changes of the local atomic-level structure in amorphous NaGaS2 and after crystallization were analyzed by high-field solid-state nuclear magnetic resonance (NMR) spectroscopy as well as by X-ray total scattering and pair distribution function (PDF) analysis. Based on quantitative analysis on the 23Na NMR spectra, modifying the annealing treatment can promote the formation of the crystalline phase up to a molar fraction of 83.8%.

NMR Investigation of the Interaction of Three Non-Steroidal Anti-Inflammatory Drugs with Human Serum Albumin.

The understanding of the interaction between non-steroidal anti-inflammatory drugs and human serum albumin plays a fundamental role in the development of new drugs and new therapeutic strategies. Several studies have been performed, nevertheless, the interaction phenomena are still not fully understood. In this work, high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy was applied to compare the strength of the interaction of diclofenac sodium salt, ketorolac tris salt and flurbiprofen sodium salt toward albumin. To this aim, mono- and bi-selective relaxation rate measurements were performed by applying selective π-pulses at the selected frequencies and by following magnetization recovery. On the basis of the dependence of relaxation parameters on albumin concentration, normalized affinity indexes were calculated for several protons of the drugs. Affinity indexes for diclofenac were about five-fold higher in comparison with ketorolac and flurbiprofen. Aromatic moieties of the three drugs and methine protons at the chiral centers of ketorolac and flurbiprofen were more involved in the interaction with albumin. In conclusion, NMR spectroscopy allows not only for the comparison of drug-to-protein affinities but also points out the nature of the drug sites that are more extensively involved in the interaction.

P.74 Using high-field magnetic resonance spectroscopy to measure muscle glycogen in patients with McArdle disease

Glycogen plays a critical role as an energy source in skeletal muscle. McArdle disease is a recessively inherited disorder in which muscle glycogen breakdown is blocked due to myophosphorylase deficiency. The patients suffer from severe exercise intolerance marked by premature fatigue with muscle contractures and episodic rhabdomyolysis. Additionally, some patients show progressive muscular atrophy when they get older, mainly in lumbar paraspinal muscles but not in thigh or calf muscles. The cause of fat replacement in older McArdle patients is unknown but could relate to a higher glycogen accumulation in their muscles. Utilizing the high sensitivity of 13C magnetic resonance spectroscopy at 7 Tesla field strength, we wanted to quantify muscle glycogen in lumbar, thigh and calf muscles in young McArdle patients as well as healthy controls to test the hypothesis of variable glycogen content in muscles of patients with McArdle disease. Preliminary results from 5 patients and 8 controls, show increased muscle glycogen concentration in the calf (4.4 times normal levels, p = 0.002), hamstrings (2.7 times normal levels, p = 0.02) and anterior thigh compartment (3.2 times normal levels, p = 0.01), while there was no difference in the lumbar muscle glycogen content vs. healthy (p = 0.6). No clear pattern of muscle glycogen distribution was seen in neither the McArdle nor the control groups. Our results are in line with previous studies in that we see a 3-5 times increase in glycogen compared to control. Surprisingly, this is not seen in the lumbar muscle group, which is the muscle group most prone to fat replacement with age. Thus, it does not appear that a difference in glycogen concentration between muscles of McArdle patients can explain the fat replacement seen in specific muscles groups of older patients.

Brain glutamate concentration in men with early psychosis: a magnetic resonance spectroscopy case\u2013control study at 7\u2009T

Abnormalities in glutamate neurotransmission are linked to psychotic symptoms and cognitive dysfunction in schizophrenia. magnetic resonance spectroscopy (MRS) provides an acceptable means of measuring glutamate in the human brain but findings from patient studies at conventional magnetic field strength show considerable heterogeneity. Ultra-high-field MRS offers greater precision in glutamate measurement, particularly in delineation of glutamate from its precursor and metabolite, glutamine. This study aimed to use high-field (7 T) MRS to measure concentrations of glutamate and glutamine in three brain regions, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and putamen (PUT), in young men with early psychosis. MRS was performed in 17 male participants with early psychosis and 18 healthy age-matched controls. Neurometabolite levels were calculated with unsuppressed water signal as the reference and corrected for individual grey matter, white matter and cerebrospinal fluid concentration. Cognitive function was measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Compared to controls, patients with early psychosis had lower concentrations of glutamate and glutamine in ACC. No differences were apparent in the DLPFC and PUT. In patients with early psychosis, there was a highly significant correlation between glutamate concentration in ACC and performance on the BACS, though the numbers available for this analysis were small. Our finding of lower glutamate levels in ACC in patients with schizophrenia is consistent with a recent meta-analysis of 7 T studies and suggests that this abnormality is present in both patients with early psychosis and those with longer-established illness. The possible link between ACC glutamate and cognitive performance requires replication in larger studies.

Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.

S7. INVESTIGATING THE LINK BETWEEN THE PERIPHERAL ENDOCANNABINOID SYSTEM AND CENTRAL GLUTAMATERGIC NEUROTRANSMISSION IN EARLY PSYCHOSIS: A 7T-MRS STUDY

BackgroundMeta-analytic evidence showed increased levels of peripheral endocannabinoid metabolites in psychotic illness. Alterations in the endocannabinoid system are believed to compromise glutamate and dopamine transmission, which play a central role in pathophysiological models of psychosis. I will present preliminary data from an ongoing high-field proton magnetic resonance spectroscopy (MRS) study aimed at investigating the association between peripheral levels of endocannabinoid system metabolites and central glutamate metabolism in individuals at their first non-affective psychotic episode (NA-FEP) and healthy controls.MethodsWe expect to recruit 17 NA-FEP and 20 healthy controls by January 2020. Currently, we recruited 12 NA-FEP and 18 healthy controls from two different research facilities (Imperial College London and University of Oxford) as part of a cross-sectional study. Participants underwent MRS scanning at 7-T with voxels placed in right dorsolateral prefrontal cortex (right-DLPFC), anterior cingulate cortex (ACC), and occipital cortex. Neuro-metabolites will be calculated using the unsuppressed water signal as reference. Endocannabinoid metabolites were quantified from serum samples, collected during the same imaging session.ResultsAnalyses are ongoing. Based on previous evidence, expected findings are: (i) reduced glutamate levels in the ACC and right-DLPFC of NA-FEP compared to controls; (ii) increased peripheral endocannabinoid metabolites in NA-FEP compared to controls; and (iii) inverse association between peripheral endocannabinoid metabolites and glutamate levels in ACC and right-DLPFC in NA-FEPDiscussionThis study will help clarifying the contribution of peripheral endocannabinoid system to central brain mechanisms of key relevance for psychotic illness. It will also add further evidence on the limited literature on high-resolution characterisation of brain metabolites in early psychosis. Strengths of the study include: (i) use of high-field MRS, which allows the estimation of glutamate-related compounds at higher precision than at lower field strength; (ii) reduced heterogeneity of the clinical sample (only male and NA-FEP). Limitations: small sample size and cross-sectional design.

Glutamate in Dorsolateral Prefrontal Cortex in Patients With Schizophrenia: A Meta-Analysis of 1-HMRS Studies

Abstract Background To date, there is no systematic overview of glutamate in dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients. We here meta-analyzed case-control studies of high-field magnetic resonance spectroscopy (1H-MRS) investigating glutamate in DLPFC. Additionally, we estimated variance ratios, to investigate homo-/heterogeneity. Methods Preregistration of the study was performed on September 20th 2019 (osf.io/5uyr6). Predefined literature search on PubMed comprised articles with search terms: (Magnetic Resonance Spectroscopy OR MRS) AND (Glutamate OR Glut* OR GLX) AND (schizophrenia OR psychosis OR schizophren*). Meta-analyses with a fixed and random-effects model with inverse variance method, DerSimonian-Laird estimator for τ2, and Cohen's d were calculated. For differences in variability, we calculated a random-effects model for measures of variance ratios. The primary study outcome was the difference in glutamate in DLPFC in cases vs. controls. Secondary outcomes were differences in variability. Results The quantitative analysis comprised n=429 patients and n=365 controls. Overall, we found no group difference (d=0.03[-0.20; 0.26],z=0.28,p=0.78). Sensitivity analysis revealed an effect for medication status (Q=8.35,p=0.039) i.e. increased glutamate in antipsychotic naive patients (d=0.46[0.08; 0.84],z=2.37,p=0.018). Concerning variance ratios, we found an effect of medication status (Q=16.95, p Conclusion We carefully interpret the higher levels and lower variability in cortical glutamate in antipsychotic naive patients as a possible key factor due to a putative allostatic mechanism. We conclude that care has to be taken when evaluating metabolite levels in clinical samples where medication might confound findings.

Designing and building a low-cost portable FT-NMR spectrometer in 2019: A modern challenge

Abstract High-field Fourier-Transform Nuclear Magnetic Resonance (FT-NMR) spectroscopy is a high performance spectroscopic technique that is essential in many analytical fields. The non-destructive nature of NMR makes it a preferred means of analyzing chemical and biological environments. Compact benchtop NMR spectrometers are low-cost alternatives to conventional high-field and high-resolution spectrometers. A research laboratory may want to develop its own compact FT-NMR spectrometer (home-built benchtop NMR) with a very low financial cost (∼10 k€). But why? First of all, to use it punctually as an additional channel (nucleus X) to a high-resolution spectrometer, and also to be able to couple it with complementary physics instruments such as an optical microscope to study spin diffusion in semiconductors, for instance. In addition, a home-built NMR spectrometer can be used with a low-field permanent magnet for the quantification of species that does not necessarily require high-resolution, avoiding the need for weekly and expensive cryogenic services. Outside the research laboratory, this portable NMR can be used for the in situ analysis of outdoor natural environments. Finally, this compact spectrometer is naturally dedicated to the teaching of NMR technique and is open to the study of the basic electronic functions that constitute an NMR spectrometer. The main question then arises: how to build a robust Home-Built” NMR? In this article, we describe the realization of an NMR instrument based on electronic components and boards (LNA, ADC, FPGA, ARM, DDS…) easily commercially available, allowing one to obtain a benchtop NMR instrument presenting both a high acquisition dynamics and a good signal-to-noise ratio.

Rostral Anterior Cingulate Glutamine/Glutamate Disbalance in Major Depressive Disorder Depends on Symptom Severity

BackgroundPatients with major depressive disorder (MDD) show glutamatergic deficits in the ventral anterior cingulate cortex. The glutamine/glutamate (Gln/Glu) ratio was proposed to be connected to glutamatergic cycling, which is hypothesized to be dysregulated in MDD. As an indicator of regional metabolite status, this ratio might be a robust state marker sensitive to clinical heterogeneity. MethodsThirty-two MDD patients (mean age 40.88 ± 13.66 years, 19 women) and control subjects (mean age 33.09 ± 8.24 years, 19 women) were compared for pregenual anterior cingulate cortex levels of Gln/Glu, Gln/total creatine (tCr), Glu/tCr, and gamma-aminobutyric acid/tCr as determined by high-field magnetic resonance spectroscopy. We tested if symptom severity (Hamilton Depression Rating Scale) and anhedonia (Snaith-Hamilton Pleasure Scale) influence the relation of metabolites to clinical symptoms. ResultsMDD patients showed higher Gln/Glu. This was driven by marginally higher Gln/tCr and nonsignificantly lower Glu/tCr. Groups defined by severity moderated relationship between Gln/Glu and the Hamilton Depression Rating Scale. Moreover, severe cases differed from both control subjects and moderate cases. Groups defined by the Snaith-Hamilton Pleasure Scale also displayed differential relationship between Gln/Glu and levels of anhedonia, predominantly driven by Gln/tCr. ConclusionsWe elaborate previous accounts of metabolite deficits in the anterior cingulate cortex toward increased Gln/Glu. There is a moderated relationship between severity and the ratio, which suggests consideration of different mechanisms or disease state for the respective subgroups in future studies.

Assessing Brain Metabolism With 7-T Proton Magnetic Resonance Spectroscopy in Patients With First-Episode Psychosis

The use of high-field magnetic resonance spectroscopy (MRS) in multiple brain regions of a large population of human participants facilitates in vivo study of localized or diffusely altered brain metabolites in patients with first-episode psychosis (FEP) compared to healthy participants. To compare metabolite levels in 5 brain regions between patients with FEP (evaluated within 2 years of onset) and healthy controls, and to explore possible associations between targeted metabolite levels and neuropsychological test performance. Cross-sectional design used 7-T MRS at a research MR imaging facility in participants recruited from clinics at the Johns Hopkins Schizophrenia Center and the local population. Eighty-one patients who had received a DSM-IV diagnosis of FEP within the last 2 years and 91 healthy age-matched (but not sex-matched) volunteers participated. Brain metabolite levels including glutamate, glutamine, γ-aminobutyric acid (GABA), N-acetylaspartate, N-acetylaspartyl glutamate, and glutathione, as well as performance on neuropsychological tests. The mean (SD) age of 81 patients with FEP was 22.3 (4.4) years and 57 were male, while the mean (SD) age of 91 healthy participants was 23.3 (3.9) years and 42 were male. Compared with healthy participants, patients with FEP had lower levels of glutamate (F1,162 = 8.63, P = .02), N-acetylaspartate (F1,161 = 5.93, P = .03), GABA (F1,163 = 6.38, P = .03), and glutathione (F1,162 = 4.79, P = .04) in the anterior cingulate (all P values are corrected for multiple comparisons); lower levels of N-acetylaspartate in the orbitofrontal region (F1,136 = 7.23, P = .05) and thalamus (F1,133 = 6.78, P = .03); and lower levels of glutathione in the thalamus (F1,135 = 7.57, P = .03). Among patients with FEP, N-acetylaspartate levels in the centrum semiovale white matter were significantly correlated with performance on neuropsychological tests, including processing speed (r = 0.48; P < .001), visual (r = 0.33; P = .04) and working (r = 0.38; P = .01) memory, and overall cognitive performance (r = 0.38; P = .01). Seven-tesla MRS offers insights into biochemical changes associated with FEP and may be a useful tool for probing brain metabolism that ranges from neurotransmission to stress-associated pathways in participants with psychosis.

Structural Differences between the Glass and Crystal Forms of the Transparent Ferroelectric Nanocomposite, LaBGeO5, from Neutron Diffraction and NMR Spectroscopy

A combination of pulsed neutron diffraction and high-field 11B nuclear magnetic resonance (NMR) spectroscopy was used to obtain structural information on the xLa2O3·(1 – x)(0.33B2O3·0.67GeO2) (x = 0, 0.20, 0.25, 0.30) glass system, as well as a crystallized sample of composition LaBGeO5. LaBGeO5 is of interest as a ferroelectric nanocomposite, as it crystallizes isochemically from the glass. The crystal structure is composed of 4-coordinated boron and germanium, together with 9-coordinated lanthanum. Our results support a model for the glass structure that is substantially different: both NMR and neutron diffraction show that the glasses contain large fractions of 3-coordinated boron as well as 4-coordinated boron, and the neutron diffraction results show clear evidence for a significant fraction of germanium with a coordination number greater than 4. Moreover, the La coordination number in the glasses is estimated as 7.4, with a typical La–O bond length of 2.52 A, based on detailed modeling of the neutro...

Neurochemical abnormalities in premanifest and early spinocerebellar ataxias.

To investigate whether early neurochemical abnormalities are detectable by high-field magnetic resonance spectroscopy (MRS) in individuals with spinocerebellar ataxias (SCAs) 1, 2, 3, and 6, including patients without manifestation of ataxia. A cohort of 100 subjects (N = 18-21 in each SCA group, including premanifest mutation carriers; mean score on the Scale for the Assessment and Rating of Ataxia [SARA] <10 for all genotypes, and 22 matched controls) was scanned at 7 Tesla to obtain neurochemical profiles of the cerebellum and brainstem. A novel multivariate approach (distance-weighted discrimination) was used to combine regional profiles into an "MRS score." MRS scores robustly distinguished individuals with SCA from controls, with misclassification rates of 0% (SCA2), 2% (SCA3), 5% (SCA1), and 17% (SCA6). Premanifest mutation carriers with estimated disease onset within 10 years had MRS scores in the range of early-manifest SCA subjects. Levels of neuronal and glial markers significantly correlated with SARA and an Activities of Daily Living score in subjects with SCA. Regional neurochemical alterations were different between SCAs at comparable disease severity, with SCA2 displaying the most extensive neurochemical abnormalities, followed by SCA1, SCA3, and SCA6. Neurochemical abnormalities are detectable in individuals before manifest disease, which may allow premanifest enrollment in future SCA trials. Correlations with ataxia and quality-of-life scores show that neurochemical levels can serve as clinically meaningful endpoints in trials. Ranking of SCA types by degree of neurochemical abnormalities indicates that the neurochemistry may reflect synaptic function or density. Ann Neurol 2018;83:816-829.

Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral Sclerosis.

The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; Rρ = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; Rρ = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; Rρ = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (mI), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rρ = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS.

Brain glutamate in anorexia nervosa: a magnetic resonance spectroscopy case control study at 7 Tesla

RationaleAnorexia nervosa (AN) is a serious psychiatric disorder with high morbidity and mortality. There are no established pharmacological treatments and the neurobiology of the condition is poorly understood. Previous studies using magnetic resonance spectroscopy (MRS) have shown that AN may be associated with reductions in indices of brain glutamate; however, at conventional field strengths (≤3 T), it is difficult to separate glutamate from its precursor and metabolite, glutamine.ObjectivesThe objective of the present study was to use high field (7 T) MRS to measure concentrations of glutamate, in three separate brain voxels, in women with AN.MethodsWe studied 13 female participants with AN and 12 healthy female controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen. Neurometabolites were calculated using the unsuppressed water signal as a reference and corrected for individual cerebrospinal fluid concentration in the voxel.ResultsWe found that participants with AN had significantly lower concentrations of glutamate in all three voxels (mean reduction 8%, p = 0.002) but glutamine levels were not altered. Concentrations of N-acetylaspartate, creatine, GABA and glutathione were also unchanged. However, inositol was lower in AN participants in anterior cingulate (p = 0.022) and occipital cortex (p = 0.002).ConclusionsWomen with AN apparently have widespread reductions in brain glutamate. Further work will be needed to assess if this change has pathophysiological relevance or whether it is a consequence of the many physical changes produced in AN by food restriction.

Brain metabolic alterations in mice subjected to postnatal traumatic stress and in their offspring

Adverse environmental and social conditions early in life have a strong impact on health. They are major risk factors for mental diseases in adulthood and, in some cases, their effects can be transmitted across generations. The consequences of detrimental stress conditions on brain metabolism across generations are not well known. Using high-field (14.1 T) magnetic resonance spectroscopy, we investigated the neurochemical profile of adult male mice exposed to traumatic stress in early postnatal life and of their offspring, and of undisturbed control mice. We found that, relative to controls, early life stress-exposed mice have metabolic alterations consistent with neuronal dysfunction, including reduced concentration of N-acetylaspartate, glutamate and γ-aminobutyrate, in the prefrontal cortex in basal conditions. Their offspring have normal neurochemical profiles in basal conditions. Remarkably, when challenged by an acute cold swim stress, the offspring has attenuated metabolic responses in the prefrontal cortex, hippocampus and striatum. In particular, the expected stress-induced reduction in the concentration of N-acetylaspartate, a putative marker of neuronal health, was prevented in the cortex and hippocampus. These findings suggest that paternal trauma can confer beneficial brain metabolism adaptations to acute stress in the offspring.

Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls.

BackgroundAbnormality in the concentration and functioning of gamma-aminobutyric acid (γ-aminobutyric acid, GABA) in the brain is not only an important hypothetical link to the cause of schizophrenia but it may also be correlated with the cognitive decline and negative symptoms of schizophrenia. Studies utilizing high field magnetic resonance spectroscopy (MRS) report abnormal density of GABA in the ventromedial prefrontal cortex (vmPFC) of patients with chronic schizophrenia, but these results may be confounded by study participants’ prior use of antipsychotic medications. AimCompare the density of GABA in the vmPFC of patients with first-episode psychosis to that in healthy controls and assess the relationship of GABA density in the vmPFC to the severity of psychotic symptoms.MethodsSingle-voxel 1H-MRS was used to assess the concentration of GABA and other metabolites in the vmPFC of 22 patients with first-episode psychosis (10 with schizophrenia and 12 with schizophreniform disorder) and 23 healthy controls. Thirteen of the 22 patients were drug-naïve and 9 had used antipsychotic medication for less than 3 days. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the severity of psychotic symptoms in the patient group.ResultsThe mean (sd) GABA density in the vmPFC was significantly higher in patients than in controls (2.28 [0.54] v. 1.93 [0.32] mM, t=2.62, p=0.012). The densities of other metabolites – including N-acetylaspartic acid (NAA), glutamic acid (GLU), and glutamine (GLN) – were not significantly different between patients and controls. Among the patients, GABA density in the vmPFC was not significantly correlated with PANSS total score or with any of the three PANSS subscale scores for positive symptoms, negative symptoms, and general psychopathology. GABA concentration was not associated with the duration of illness, but it was significantly correlated with patient age (r=0.47, p=0.026).ConclusionElevation of GABA density in the vmPFC of patients with first-episode psychosis confirms that this abnormality is independent of medication use. The failure to find a correlation of GABA density in the vmPFC with the severity of psychotic symptoms needs to be confirmed in larger studies, but it suggests that there are several intervening steps between brain pathology and clinical symptoms.

Relating 139La Quadrupolar Coupling Constants to Polyhedral Distortion in Crystalline Structures

A broad series of crystalline lanthanum oxide-based materials has been investigated through high-field 139La solid state nuclear magnetic resonance (ssNMR) spectroscopy and ab initio density functional theory (DFT) calculations. The 139La NMR spectra of LaBGeO5, LaBSiO5, LaBO3, LaPO4·1.8H2O, La2(SO4)3·9H2O, and La2(CO3)3·8H2O are reported for the first time. Both newly reported and literature values of 139La quadrupolar coupling constants (CQ) are related to various quantitative expressions of polyhedral distortion, including sphericity (Σ) and ellipsoid span (ϵ). The compounds were separated into two groups based upon their polyhedral distortion behavior: compounds with the general formula LaMO3, where M is a trivalent cation; compounds with different general formulas. The 139La CQ of the LaMO3 family was found to correlate best with ϵ. The 139La CQ of non-LaMO3 compounds correlates adequately to ϵ but is better described by Σ. The 139La isotropic chemical shift (δisoCS) of the non-LaMO3 compounds is neg...

Quantification of N-Acetyl Aspartyl Glutamate in Human Brain using Proton Magnetic Resonance Spectroscopy at 7 T

UDC 543.422.25:611.81 The separation of N-acetyl aspartyl glutamate (NAAG) from N-acetyl aspartate (NAA) and other metabolites, such as glutamate, by in vivo proton magnetic resonance spectroscopy at 7 T is described. This method is based on the stimulated echo acquisition mode (STEAM), with short and long echo time (TE) and allows quantitative measurements of NAAG in the parietal and pregenual anterior cingulate cortex (pgACC) of human brain. Two base- sets for the LCModel have been established using nuclear magnetic resonance simulator software (NMR-SIM). Six healthy volunteers (age 25-35 years) have been examined at 7 T. It has been established that NAAG can be separated and quantifi ed in the parietal location and does not get quantifi ed in the pgACC location when using a short echo time, TE = 20 ms. On the other hand, by using a long echo time, TE = 74 ms, NAAG can be quantifi ed in pgACC structures. LCModel. Introduction. N-Acetylaspartylglutamic acid (NAAG) is a neuropeptide that is the third most prevalent neurotransmitter in the human brain (1). NAAG is produced by the coupling between a glutamic acid (Glu) and the N-acetylaspartic acid (NAA) via a peptide bond. Therefore, it may be diffi cult to distinguish between them on account of the similarity of the chemical structure. In human studies, it has been suggested that NAAG levels are abnormal in patients with schizophrenia (2) and decreased in amyotrophic lateral sclerosis (ALS) (3). In a previous study (4), it had been diffi cult to distinguish NAAG from NAA and Glu using proton magnetic resonance spectroscopy (MRS) at 3 T. As the dominant signal of the NAAG spectrum from the N-acetyl proton resonance peak is located at 2.05 ppm, which is 0.03 ppm away from the corresponding NAA signal at 2.02 ppm (5), a high resolution of metabolite peaks can be obtained using ultrahigh-fi eld strengths such as 7 T (6, 7) or at high fi elds (2 or 3 T), with unusual shimming (8). Proton magnetic resonance spectroscopy provides markers for various human brain diseases (9, 10). Some of the important measurement characteristics of the MRS technique are the signal-to-noise ratio (SNR), spatial and spectral resolution, as well as scan time; thus, several localization methods have been proposed. Single volume spectroscopy (SVS) localization techniques, with pulse sequences based on spin echoes (PRESS) (11) or stimulated echoes (STEAM) (12), provide the highest spectral quality (13), as the lower magnetic fi eld strengths result in a peak overlap of the human brain metabolites, such as, NAA with NAAG. Besides, standard spectroscopic sequences such as STEAM or PRESS will suffer if limited transmitter voltage takes place. This results in a reduced excitation flip angle and consequently insuffi cient excitation in the volume of interest (VOI). Moreover, previous studies have shown that the increase in magnetic field strength increases the 1 H NMR spectral peak separation and SNR and thus provides higher sensitivity when compared with lower field strengths (14, 15). With standard radio-frequency (RF) amplifiers and volume RF coils at 7 T, short 180° refocusing pulses are diffi cult to achieve in most parts of the brain. Therefore, earlier, high field MRS studies frequently employed surface coils with locally higher RF fi eld amplitude (16, 17). However, not all brain areas can be adequately examined using surface coils. As the goal of this study is to quantify the NAAG concentrations in different brain structures, STEAM with short echo time benefits, from reduced signal decay, because of the J-evolution of the coupled spin system, allows a more precise quantification of the metabolites, especially with a short T2 relaxation time (18). Thus, short echo times have been used in several studies (19). In the current study, echo time (TE) was selected to be short and long 20 and 74 ms, respectively. Although earlier studies had employed STEAM with ultrashort echo times (6 ms), they were limited by the surface coils that prevented detection in the deep brain regions (20). Also, a quadrature (transmit/receive) surface RF coil or a half-volume RF coil have been used for the