Magnetic Resonance Spectroscopy Measurements Research Articles

Carbon Dioxide Contamination of Aqueous Morpholine Solutions and Effects on Secondary Coolant Chemistry Under CANDU Conditions

Exposure to air can cause amine solutions in CANada Deuterium Uranium (CANDU) reactor secondary coolant circuit feed tanks to absorb carbon dioxide (CO2). Likewise, carbon dioxide can be absorbed directly into the amine-containing secondary coolant by air ingress during shutdown, lay-up, and startup. Sampling operations, including transferring the sample to the laboratory and subsequent analyses, can also provide opportunities for CO2 contamination. This paper reports the results of laboratory and chemical modeling studies to examine the effects of CO2 contamination on aqueous morpholine solutions. The chemistry of CO2 uptake by feed tanks containing up to 50 wt% (11.5 mol·kg−1) morpholine at 25°C was modeled using the OLI Studio 9.5.2 chemical equilibrium model, and the speciation was confirmed by 13C nuclear magnetic resonance spectroscopy (NMR) measurements. The effects of CO2 contamination on the pH of the secondary coolant containing 60 ppm (0.006 wt%, 7.00 × 10−4 mol·kg−1) morpholine and the resulting effects on the solubility of magnetite and nickel oxide from 25°C and 250°C at steam saturation were modeled as a function of CO2 loading using the Electrical Power Research Institute chemical modeling software MULTEQ v.8. The chemical modeling calculations show that concentrated alkaline morpholine solutions at room temperature and pressure would be expected to have a strong tendency to absorb CO2 and have additional uptake abilities due to the formation of morpholine carbamates. For dilute morpholine solutions at room temperature and pressure, the solutions are still sufficiently alkaline to absorb enough CO2 to cause a measurable change in the pH of the secondary coolant. This effect was shown to be negligible under reactor operating conditions. The absorption of CO2 would potentially have the most effect on either unprotected feed tanks or during lay-up conditions in the steam generators, as it could depress the pH of the lay-up solution and adversely affect the rate of corrosion in the internal components of the steam generators (e.g., carbon steel materials). The 13C NMR measurements on samples of 50 wt% aqueous morpholine solutions from feed tanks at the Ontario Power Generation’s Pickering Nuclear Generating Station found that CO2 was below the 0.02 wt% detection limit, and suggest that the procedures used to avoid CO2 contamination in feed tanks are effective. The 13C NMR was shown to be an effective tool for monitoring CO2 uptake by morpholine solution in the feed tanks under conditions in which they may have undergone abnormal exposure to air.

Proton MR Spectroscopy Measurements of White and Brown Adipose Tissue in Healthy Humans: Relaxation Parameters and Unsaturated Fatty Acids.

Background Activation of brown adipose tissue (BAT) in rodents increases lipolysis in white adipose tissue (WAT) and improves glucose tolerance. Adult humans can have metabolically active BAT. Implications for diabetes and obesity in humans require a better characterization of BAT in humans. Purpose To study fat depots with localized proton MR spectroscopy relaxometry and to identify differences between WAT and fluorine 18 fluorodeoxyglucose (FDG) PET/CT proven cold-activated BAT in humans. Materials and Methods Participants were consecutively enrolled in this prospective study (ClinicalTrials.gov identifiers: NCT01568671 and NCT01399385) from August 2016 to May 2019. Supraclavicular potential BAT regions were localized with MRI. Proton densities, T1, and T2 were measured with localized MR spectroscopy in potential BAT and in subcutaneous WAT. FDG PET/CT after cold stimulation was used to retrospectively identify active supraclavicular BAT or supraclavicular quiescent adipose tissue (QAT) regions. MR spectroscopy results from BAT and WAT were compared with grouped and paired tests. Results Of 21 healthy participants (mean age, 36 years ± 16 [standard deviation]; 13 men) FDG PET/CT showed active BAT in 24 MR spectroscopy-targeted regions in 16 participants (eight men). Four men had QAT. The T2 for methylene protons was shorter in BAT (mean, 69 msec ± 6, 24 regions) than in WAT (mean, 83 msec ± 3, 18 regions, P < .01) and QAT (mean, 78 msec ± 2, five regions, P < .01). A T2 cut-off value of 76 msec enabled the differentiation of BAT from WAT or QAT with a sensitivity of 85% and a specificity of 95%. Densities of protons adjacent and between double bonds were 33% and 24% lower, respectively, in BAT compared with those in WAT (P = .01 and P = .03, respectively), indicating a lower content of unsaturated and polyunsaturated fatty acids, respectively, in BAT compared with WAT. Conclusion Proton MR spectroscopy showed shorter T2 and lower unsaturated fatty acids in brown adipose tissue (BAT) than that in white adipose tissue in healthy humans. It was feasible to identify BAT with MR spectroscopy without the use of PET/CT or cold stimulation. © RSNA, 2021 See also the editorial by Barker in this issue. Online supplemental material is available for this article.

GABAergic cortical network physiology in frontotemporal lobar degeneration.

The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive and physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify the GABAergic impairment and its restoration with dynamic causal modelling of a double-blind placebo-controlled crossover pharmaco-magnetoencephalography study. We analysed 17 patients with bvFTD, 15 patients with progressive supranuclear palsy, and 20 healthy age- and gender-matched controls. In addition to neuropsychological assessment and structural MRI, participants undertook two magnetoencephalography sessions using a roving auditory oddball paradigm: once on placebo and once on 10 mg of the oral GABA reuptake inhibitor tiagabine. A subgroup underwent ultrahigh-field magnetic resonance spectroscopy measurement of GABA concentration, which was reduced among patients. We identified deficits in frontotemporal processing using conductance-based biophysical models of local and global neuronal networks. The clinical relevance of this physiological deficit is indicated by the correlation between top-down connectivity from frontal to temporal cortex and clinical measures of cognitive and behavioural change. A critical validation of the biophysical modelling approach was evidence from parametric empirical Bayes analysis that GABA levels in patients, measured by spectroscopy, were related to posterior estimates of patients’ GABAergic synaptic connectivity. Further evidence for the role of GABA in frontotemporal lobar degeneration came from confirmation that the effects of tiagabine on local circuits depended not only on participant group, but also on individual baseline GABA levels. Specifically, the phasic inhibition of deep cortico-cortical pyramidal neurons following tiagabine, but not placebo, was a function of GABA concentration. The study provides proof-of-concept for the potential of dynamic causal modelling to elucidate mechanisms of human neurodegenerative disease, and explains the variation in response to candidate therapies among patients. The laminar- and neurotransmitter-specific features of the modelling framework, can be used to study other treatment approaches and disorders. In the context of frontotemporal lobar degeneration, we suggest that neurophysiological restoration in selected patients, by targeting neurotransmitter deficits, could be used to bridge between clinical and preclinical models of disease, and inform the personalized selection of drugs and stratification of patients for future clinical trials.

MR spectroscopy and imaging-derived measurements in the supplementary motor area for biomarkers of amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) requires both upper and lower motor neuron signs. However, quite a few patients with ALS lack the upper motor neuron sign during the disease. This study sought to investigate whether metabolites, including glutamate (Glu), N-acetyl aspartate (NAA), and gamma aminobutyric acid (GABA), in the supplementary motor area (SMA) measured by magnetic resonance spectroscopy (MRS), could be a surrogate biomarker for ALS. Twenty-five patients with ALS and 12 controls underwent 3.0-T MR scanning, which measured Glu, NAA, and GABA. Finally, receiver operating characteristic (ROC) curves were created and the area under curve (AUC) was calculated to assess the diagnostic power. Logistic regression analysis revealed the usefulness of both Glu and NAA for the differentiation of ALS from controls (Glu, P = 0.009; NAA, P = 0.033). The ratio of Glu to NAA or GABA was significantly increased in patients with ALS (Glu/NAA, P = 0.027; Glu/GABA, P = 0.003). Both the AUCs were more than 0.7, with high specificity but low sensitivity. The present findings might indicate that both the Glu/NAA and the Glu/GABA ratios in the SMA could be potential biomarkers for the diagnosis of ALS.

Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS

Gamma-aminobutyric acid (GABA) and glutamate are the primary neurotransmitters responsible for modulating excitatory and inhibitory signalling within the human brain. Dysfunctional GABAergic and glutamatergic signalling has been identified as a key factor in a range of neuropsychiatric conditions; hence measurement and modulation of these neurometabolites is important for improving our understanding of neuropsychiatric conditions and treatment options. Gabapentin (GBP) is one of several drugs developed to increase GABA levels and is routinely prescribed for conditions such as epilepsy and neuralgia. While animal and human studies indicate that GBP can elevate GABA levels, its exact mechanisms of action are not fully understood, although animal studies indicate that GBP does not have a direct effect upon GABAergic receptors.To investigate the impact of acute GBP administration in the human motor system we used two complimentary approaches – transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). MRS and TMS measures of GABA have repeatedly been found to be uncorrelated and are likely to reflect different pools of synaptic and extra synaptic GABA, hence, measuring both within the same participants allows for an in-depth assessment of GBP effects.Despite significantly increased ratings of fatigue and tiredness within the GBP group, we failed to find any statistically significant changes in our MRS or TMS measures of GABA. Measures of MRS Glutamate (glu) and glutamine (gln) were also not affected by the administration of GBP. These findings are important as they run counter to previous work, and suggest that the effect of an acute dose of GBP is likely to be subject to substantial individual variation, with timing of measures particularly likely to impact observed effects. These findings have implications for the use of acute GBP dosing as a means to explore GABAergic function in health and disease.

Composition of the white precipitate formed on the surface of damaged triacetyl cellulose-based motion picture films

To achieve a better understanding of the “vinegar syndrome” phenomenon, which has caused serious damage to triacetyl cellulose-based motion picture films, the white powder obtained from damaged film surfaces was analysed in this study. The powder was found to be soluble in acetone, diethyl ether, dimethylformamide, and chloroform, but insoluble in water. From the results of 1H, 13C and 31P nuclear magnetic resonance spectroscopy, mass spectrometry, and X-ray fluorescence measurements, it was concluded that the white precipitate had a molecular weight of 326 amu and was composed of triphenyl phosphate (C18H15O4P).

Proton MR spectroscopic features of the cisternal segment of the trigeminal nerve in patients with trigeminal neuralgia: A pilot study

PurposeTo investigate normal quantitative proton magnetic resonance spectroscopy (MRS) features of the cisternal segment of the trigeminal nerve and evaluate possible metabolite concentration differences in the affected and unaffected nerves of trigeminal neuralgia patients. Material and methodsA total of 33 consecutive patients who underwent a MR study of the internal auditory canal/posterior fossa and dedicated trigeminal nerve multivoxel MRS were enrolled. Measurements of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), myoinositol (mI), glutamate-glutamine (Glx) concentrations, and ratios of NAA-to-Cr, Cho-to-Cr, and Cho-to-NAA were automatically calculated by the dedicated software. Vascular conflicts were also recorded. ResultsThe mean Cr concentration was significantly higher on the affected sides in all parts of the nerve (p < 0.05), while the mean NAA concentration was significantly higher in only the distal portion (p = 0.04). Mean mI concentration was significantly higher in the middle and distal parts (p < 0.05). NAA-to-Cr ratio was significantly higher in the proximal and middle parts (p < 0.05), while Cho-to-Cr ratio was significantly higher only in the middle portion (p = 0.028). Finally, the Cho-to-NAA ratio was significantly higher only in the distal portion (p = 0.04). Vascular conflicts were observed in 24 patients (72.7%), and in 20 of them (60.6%) the conflict was on the same side as the neuralgia symptoms. ConclusionAlthough the detected statistical relationships were variable in the spectroscopic measurements, metabolite concentrations and ratios were successfully exhibited in all patients. Features of a normal trigeminal nerve were able to determine by MRS. All calculated metabolite concentrations were higher in the affected nerves; however, only some of them were statistically significant. No statistically significant relationships were found between the MRS measurements and nerves with and without vascular compression.

Low- and High-resolution Dynamic Analyses for Magnetic Resonance Spectroscopy Data.

Magnetic resonance spectroscopy (MRS) can be used to measure in vivo concentrations of neurometabolites. This information can be used to identify neurotransmitter involvement in healthy (e.g., perceptual and cognitive processes) and unhealthy brain function (e.g., neurological and psychiatric illnesses). The standard approach for analyzing MRS data is to combine spectral transients acquired over a ~10 min scan to yield a single estimate that reflects the average metabolite concentration during that period. The temporal resolution of metabolite measurements is sacrificed in this manner to achieve a sufficient signal-to-noise ratio to produce a reliable estimate. Here we introduce two analyses that can be used to increase the temporal resolution of neurometabolite estimates produced from MRS measurements. The first analysis uses a sliding window approach to create a smoothed trace of neurometabolite concentration for each MRS scan. The second analysis combines transients across participants, rather than time, producing a single "group trace" with the highest possible temporal resolution achievable with the data. These analyses advance MRS beyond the current "static" application by allowing researchers to measure dynamic changes in neurometabolite concentration and expanding the types of questions that the technique can be used to address.

Occipital gamma-aminobutyric acid and glutamate-glutamine alterations in major depressive disorder: An mrs study and meta-analysis

The neurotransmitters GABA and glutamate have been suggested to play a role in Major Depressive Disorder (MDD) through an imbalance between cortical inhibition and excitation. This effect has been highlighted in higher brain areas, such as the prefrontal cortex, but has also been posited in basic sensory cortices. Based on this, magnetic resonance spectroscopy (MRS) was used to investigate potential changes to GABA+ and glutamate+glutamine (Glx) concentrations within the occipital cortex in MDD patients (n = 25) and healthy controls (n = 25). No difference in occipital GABA+ or Glx concentrations, nor in the GABA+/Glx ratio, was found between groups. An analysis of an extended MDD patient and unmatched control dataset (n = 90) found no correlation between metabolite concentrations and depressive symptoms. These results were integrated with prior studies through metabolite-specific meta-analyses, revealing no difference in occipital GABA and Glx concentrations between patients and controls. An effect of publication year on GABA group differences was found, suggesting that previously reported results may have been artifacts of measurement accuracy. Taken together, our results suggest that, contrary to some prior reports, MRS measurements of occipital GABA and Glx do not differ between MDD patients and controls.

One-pot synthesis of P3HT–CdE (E=S, Se, Te) nanocomposites using conjugated polymer-grafted precursors

A simple one-pot synthetic strategy toward crafting semiconductor organic–inorganic nanocomposites composed of conjugated polymer poly(3-hexylthiphene) (P3HT) in close contact with CdE (E=S, Se, and Te) nanocrystals was introduced. Bifunctional ligand 4-azidobenzoic acid (BA-N3) that possesses two end functionalities at each end was employed, enabling the coordination of BA-N3 with Cd first to yield Cd-carboxylic acid complexes (Cd-BA-N3) followed by the subsequent click reaction between Cd-BA-N3 and ethynyl-terminated P3HT (P3HT–≡) to produce P3HT-grafted Cd complexes (Cd-BA-P3HT). Finally, injection of precursors resulted in P3HT-tethered CdE NC (E=S, Se, and Te) nanocomposites. The success of click reaction was confirmed by the Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy measurements. The photophysical properties such as charge transfer characteristics were corroborated with absorbance and photoluminescence characterization. Notably, this strategy circumvents the use of insulating fatty ligands, thus dispensing the need for tedious ligand exchange procedure.

Transcranial Magnetic Stimulation and H1-Magnetic Resonance Spectroscopy Measures of Excitation and Inhibition Following Lorazepam Administration

This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABAA receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate + glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABAA-receptor mediated motor cortex inhibition (short intracortical inhibition (SICI)). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.

Nuclear magnetic resonance spin-lattice relaxation of lithium ions in aqueous solution by NMR and molecular dynamics.

We study the aqueous solvation dynamics of lithium ions using nuclear magnetic resonance spectroscopy, molecular dynamics, and viscosity measurements. Several relaxation mechanisms are examined to explain the strong increases of spin-lattice relaxation toward high concentrations. The use of both 6Li and 7Li isotopes is helpful to identify the quadrupolar contribution to the relaxation rate. In particular, it is found that the quadrupolar interaction constitutes the strongest contribution above a concentration of ∼10 molal. The next-strongest contribution arises from interactions that scale with the square of the gyromagnetic ratio (mostly the dipolar interaction), and the experimental relaxation rates appear to be fully accounted for when these mechanisms are combined over the concentration range up to the saturation concentration. The study of solvation dynamics, particularly at high concentrations, could be of relevance for electrolyte dynamics in aqueous Li-ion rechargeable batteries.

Synthesis and Stabilization of Gold Nanoparticles Using Water-Soluble Synthetic and Natural Polymers.

Gold nanoparticles (AuNPs) were synthesized and stabilized using the one-pot method and growth seeding, through utilization of synthetic polymers, including poly(N-vinylpyrrolidone) (PVP), poly(ethylene glycol) (PEG), and poly(vinylcaprolactame) (PVCL), as well as natural polysaccharides, including gellan, welan, pectin, and κ-carrageenan. The absorption spectra, average hydrodynamic size, ζ-potential, and morphology of the gold nanoparticles were evaluated based on various factors, such as polymer concentration, molecular mass of polymers, temperature, and storage time. The optimal polymer concentration for stabilization of AuNPs was found to be 4.0 wt % for PVP, 0.5 wt % for gellan, and 0.2 wt % for pectin, welan, and κ-carrageenan. The values of the ζ-potential of polymer-stabilized AuNPs show that their surfaces are negatively charged. Most of the AuNPs are polydisperse particles, though very monodisperse AuNPs were detected in the presence of a 0.5 wt % gellan solution. At a constant polymer concentration of PVP (4 wt %), the average size of the PVP–AuNPs decreased with the decrease of molecular weight, and in the following order: PVP 350 kDa (~25 nm) > PVP 40 kDa (~8 nm) > PVP 10 kDa (~4 nm). The combination of Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopy revealed that the functional groups of polymers that are responsible for stabilization of AuNPs are lactam ring in PVP, carboxylic groups in gellan and welan, esterified carboxylic groups in pectin, and SO2 groups in κ-carrageenan. Viscometric and proton nuclear magnetic resonance (1H NMR) spectroscopic measurements showed that the temperature-dependent change in the size of AuNPs, and the gradual increase of the intensity of AuNPs at 550 nm in the presence of gellan, is due to the rigid and disordered conformation of gellan that affects the stabilization of AuNPs. The AuNPs synthesized in the presence of water-soluble polymers were stable over a period of 36 days. Preliminary results on the synthesis and characterization of gold nanorods stabilized by polymers are also presented.

Low-Density Lipoprotein Subfractionation: What Is the Role of the Lab When Reporting Discrepant Results?

Abstract Plasma concentrations of low-density-lipoprotein cholesterol (LDL-C) are directly associated with risk for coronary artery disease (CAD). Multisociety guidelines define LDL-C&amp;gt;160mg/dL as a risk factor for CAD and LDL-C&amp;gt;190mg/dL as an indication for lipid lowering medication, regardless of other clinical factors. Subfractionation of LDL according to size (LDL-s) enables differentiation between two LDL phenotypes: large-buoyant LDL and small-dense LDL. The small-dense LDL phenotype reportedly conveys increased risk for CAD. Major societies do not recommend LDL subfractions be used for clinical decision making and most payers do not cover LDL subfraction testing. Despite these restrictions, LDL subfraction is routinely requested by clinicians. Nuclear magnetic resonance (NMR) spectroscopy measures LDL-C and LDL-s. Following inquiries regarding interpretation of conflicting LDL-C and LDL-s results, we investigated associations between LDL-C and LDL-s measured by NMR in order to determine how often they provide contradicting or additive information. Verification of NMR LDL-C accuracy was confirmed by ß-quantification in a subset of patient samples (n=250). The average bias was -4.5mg/dL and the correlation coefficient was 0.92. High-risk was defined as LDL-C&amp;gt;160mg/dL or LDL-s&amp;lt;20.5 nm (small-dense LDL); and low-risk was defined as LDL-C&amp;lt;70mg/dL or LDL-s&amp;gt;20.5nm (large-buoyant LDL). In 26,710 clinical NMR analyses, the median LDL-C was 94.0mg/dL (range:5-436mg/dL) with median LDL-s of 20.8 nm (range:19.4–23.0nm). LDL-s moderately correlated with LDL-C (Ï#129;=0.51;p&amp;lt;0.01). Small-dense-LDL was identified in only 18% (407/2,191) of patients with elevated LDL-C (&amp;gt;160mg/dL) and was more common (73.2% of 6,093) in patients with low LDL-C (&amp;lt;70mg/dL;p&amp;lt;0.001). Associations with CAD were investigated among patients without cholesterol-lowering medication treatment referred for angiography (n=356). CAD (defined as stenosis &amp;gt;50% in one or more coronary artery) was diagnosed in 14% (1/7) of subjects with low LDL-C (&amp;lt;70mg/dL) compared to 59% (47/80) of subjects with elevated LDL-C (p=0.01). When stratifying by LDL-s, CAD was diagnosed in 50% (57/115) of subjects with small-dense LDL compared to 43% (104/241) of subjects with large-buoyant LDL (p=0.2). Small-dense LDL was identified in only 33% (26/80) of cases with elevated LDL-C. Limiting to subjects with elevated LDL-C, CAD was diagnosed in 50% (13/26) of subjects with concordant (high-risk) small-dense LDL compared to 61% (33/54) of subjects with discordant (low-risk) large-buoyant LDL (LDL-s&amp;gt;20.5nm) (p=0.3). Our data confirm that LDL-s subfraction measured by NMR is reported discordantly in most cases when LDL-C is unequivocally high or low. Furthermore, CAD diagnosis was significantly associated with LDL-C, but not with LDL-s. Our data also show that in discrepant samples, elevated LDL-C correlates better with disease state compared to LDL-s. Therefore, LDL-s should not be used to justify treatment decisions in patients with elevated LDL-C. Laboratories should consider carefully whether or not to report LDL-s when it is known that misleading and discordant values will be reported in a majority of cases.

Resolving the discrepancy between theoretical and experimental polarization of hyperpolarized 129Xe using numerical simulations and in situ optical spectroscopy

For emerging biomedical applications of hyperpolarized xenon, the ability to obtain reliably high nuclear spin polarization levels is paramount. Yet, experimental nuclear spin polarization levels of xenon are highly variable and, more than often than not, well below what theory predicts. Despite rigorous and well-studied theoretical models for hyperpolarization and continuous-flow spin-exchange optical pumping (SEOP), there remains a substantial discrepancy between the theoretical and experimental polarization of 129Xe; inexplicably, seemingly similar experimental parameters can yield very different polarization values. In this paper, the validity of the assumptions typically made about the thermodynamic state of the Rb vapor inside the optical pumping cell and the gas dynamics are investigated through finite element analysis simulations of realistic optical pumping cell models, while in situ optical and nuclear magnetic resonance spectroscopy measurements are used to validate the results of the simulations. Our results show that shorter xenon gas residence times and lower Rb vapor densities than those predicted by empirical saturated vapor pressure curves, along with incorrect SEOP parameters, are the primary cause of the discrepancy between theoretical and experimental polarization values reported in the literature.

Correlations between DTI-derived metrics and MRS metabolites in tumour regions of glioblastoma: a pilot study.

IntroductionSpecific correlations among diffusion tensor imaging (DTI)-derived metrics and magnetic resonance spectroscopy (MRS) metabolite ratios in brains with glioblastoma are still not completely understood.Patients and methodsWe made retrospective cohort study. MRS ratios (choline-to-N-acetyl aspartate [Cho/NAA], lipids and lactate to creatine [LL/Cr], and myo-inositol/creatine [mI/Cr]) were correlated with eleven DTI biomarkers: mean diffusivity (MD), fractional anisotropy (FA), pure isotropic diffusion (p), pure anisotropic diffusion (q), the total magnitude of the diffusion tensor (L), linear tensor (Cl), planar tensor (Cp), spherical tensor (Cs), relative anisotropy (RA), axial diffusivity (AD) and radial diffusivity (RD) at the same regions: enhanced rim, peritumoral oedema and normal-appearing white matter. Correlational analyses of 546 MRS and DTI measurements used Spearman coefficient.ResultsAt the enhancing rim we found four significant correlations: FA ⇔ LL/Cr, Rs = -.364, p = .034; Cp ⇔ LL/Cr, Rs = .362, p = .035; q ⇔ LL/Cr, Rs = -.349, p = .035; RA ⇔ LL/Cr, Rs = -.357, p = .038. Another ten pairs of significant correlations were found in the peritumoral edema: AD ⇔ LL/Cr, AD ⇔ mI/Cr, MD ⇔ LL/Cr, MD ⇔ mI/Cr, p ⇔ LL/Cr, p ⇔ mI/ Cr, RD ⇔ mI/Cr, RD ⇔ mI/Cr, L ⇔ LL/Cr, L ⇔ mI/Cr.ConclusionsDTI and MRS biomarkers answer different questions; peritumoral oedema represents the biggest challenge with at least ten significant correlations between DTI and MRS that need additional studies. The fact that DTI and MRS measures are not specific of one histologic type of tumour broadens their application to a wider variety of intracranial pathologies.

Li7GeS5Br-An Argyrodite Li-Ion Conductor Prepared by Mechanochemical Synthesis.

In recent years, the search for glassy and ceramic Li+ superionic conductors has received significant attention, mainly due to the renaissance of interest in all-solid-state batteries. Here, we report the mechanochemical synthesis of metastable Li7GeS5Br, which is, to the best of our knowledge, the first compound of the Li2S-GeS2-LiBr system. Applying combined synchrotron X-ray diffraction and neutron powder diffraction, we show Li7GeS5Br to crystallize in the F4̅3m space group and to be isostructural with argyrodite-type Li6PS5Br, but with a distinct difference in the S2-/Br- site disorder (and improved anodic stability). Electrochemical impedance spectroscopy indicates an electrical (ionic) conductivity of 0.63 mS cm-1 at 298 K, with an activation energy for conduction of 0.43 eV. This is supported by temperature-dependent 7Li pulsed-field gradient-nuclear magnetic resonance spectroscopy measurements. Overall, the results demonstrate that novel (metastable) argyrodite-type solid electrolytes can be prepared via mechanochemistry that are not accessible by conventional solid-state synthesis routes.

Lactate as clinical tumour biomarker: Optimization of lactate detection and quantification in MR spectroscopic imaging of glioblastomas

PurposeIncreased lactate (Lac) level in brain tumours is in vivo detectable by 1H MR spectroscopy (MRS) but is frequently overlapped by strong lipid signals, which either leads to a weak quality of the Lac signal or even inhibit its detection. We sought to optimize the separation of Lac from lipid signals in intermediate-echo time MRS acquisitions thus allowing its applicability as clinical biomarker in glioblastomas. MethodsData of 27 patients with glioblastoma multiforme (GBM) were analysed using standard post-processing software as well as in-house modified technique based on the same commercially available software. The patients’ Lac concentration values provided by the MRS post-processing technique were converted to realistic concentrations by using an appropriately calibrated phantom. The Cramér-Rao lower bound (%CR) was the principal criterion for estimating the quality of the MRS post-processing results. ResultsBased on the ex vivo calibration, the analysis of the in vivo MR spectroscopy measurements led to an improvement of the %CR(Lac) value from 18 % to 8 %. In a single case, the detection of Lac was achievable only by the modified technique, as Lac signal was contaminated with lipids using the standard analysis. The resulting in vivo Lac values from the modified analysis (median: 4.77 mmol/l, range: 1.5–9.2) were considered as a realistic order of magnitude for the metabolite concentrations, whereas no Lac was identified in the normal appearing white matter. This qualified also Lac mapping as a biomarker for regional heterogeneity in GBM. ConclusionsThe proposed methodology is a promising first step for more reliable analysis of Lac signal, decontaminating it from lipid peaks in MRS, and may help to establish Lac as a biomarker for brain tumours in clinical routine.

Combination treatments with therapeutic hypothermia for hypoxic‐ischemic neuroprotection

Therapeutic hypothermia is now proven to reduce death or disability in term and near-term born infants with moderate to severe hypoxic-ischemic encephalopathy. Nevertheless, many infants still survive with disability, despite treatment with hypothermia. Recent preclinical and clinical studies suggest that current protocols for therapeutic hypothermia are near-optimal. The obvious strategy, in addition to improving early initiation of therapeutic hypothermia after birth, is to combine hypothermia with other neuroprotective agents. We review evidence that the mechanisms of action of many promising agents overlap with the anti-excitotoxic, anti-apoptotic, and anti-inflammatory mechanisms of hypothermia, leading to a lack of benefit from combination treatment. Moreover, even apparently beneficial combinations have failed to translate in clinical trials. These considerations highlight the need for preclinical studies to test clinically realistic protocols of timing and duration of treatment, before committing to large randomized controlled trials.

Effect of Long-term Transcranial Direct Current Stimulation on Glx and GABA: A Pilot Study.

Previous studies have demonstrated that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) can enhance working memory. However, the mechanism underlying the long-term tDCS is still unclear. This pilot study aims to examine neurotransmitters such as gamma-aminobutyric (GABA) and Glx (a measure of glutamate and glutamine combined) and working memory in response to the long-term anodal tDCS over dlPFC. Six healthy, right-handed young adults enrolled in this study received 2-mA anodal tDCS over dlPFC within 4 weeks. Long-term tDCS means that it was applied 5 times per week for the first two weeks and once for the last two weeks with 30 min each time. The other six participants were enrolled as the control group without stimulation for testing the baseline enhancement of working memory due to learning. The GABA and Glx levels were assessed by Magnetic Resonance Spectroscopy (MRS), while a 3-back task was performed to assess working memory. Data were collected at the beginning of the experiment, after two-week tDCS and at the end of the experiment. We found that the working memory was not significantly enhanced by the first two-week tDCS because the accuracy of response in 3-back was not significantly increased compared to the control group. Meanwhile, there were no significant changes in the levels of GABA. However, the Glx level was found significantly decreased in both 2- and 4-week MRS measurements. The observation that the long-term tDCS causes the decrease of excitatory neurotransmitters implies the different underlying mechanisms between the long-term tDCS and the single one.