Localized Proton Magnetic Resonance Spectroscopy Research Articles

In vivo 1 H MR spectroscopy with J-refocusing.

The goal of this study was to propose a novel localized proton MR spectroscopy (MRS) sequence that reduces signal loss due to J-modulation in the rat brain in vivo. Sprague-Dawley rats were studied at 9.4 T. A semi-LASER sequence with evenly distributed echo-time (TE ) was used, and a 90° J-refocusing pulse was inserted at TE /2. Proton spectra were acquired at two TE s (30 and 68 ms), with and without the J-refocused pulse. Data were processed in MATLAB and quantified with LCModel. The J-refocused spectrum acquired at TE = 30 ms did not show any signal losses due to J-modulation and had comparable spectral pattern to the one acquired with semi-LASER using the minimum achievable TE . Higher signal amplitudes for glutamine, γ-aminobutyric acid and glutathione led to more reliable quantification precision for these metabolites. The refocused signal intensities at TE = 68 ms were also unaffected by J-modulation but were smaller than the signals at TE = 30 ms mainly due to transverse T2 relaxation of metabolites. The proposed localized MRS sequence will be beneficial in both animal and human MRS studies when using ultra-short TE is not possible while also providing more reliable quantification precision for J-coupled metabolites.

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.

Proton magnetic resonance spectroscopy as an alternative method for quantitative assessment of mineral bone density

Aims: 1) To evaluate an association between the fat fraction (FF) and bone mineral density (BMD) measured by localized proton magnetic resonance spectroscopy (1H-MRS) and quantitative computed tomography (QCT) densitometry, respectively, in healthy vertebrae of children after a compression fracture; 2) To compare the FF and BMD values with the severity of the compression vertebrae fractures.Materials and methods: Twenty (20) patients (aged 11.1±2.1 years) with a trauma-induced compression vertebral fractures participated in the study. The BMD of L3, L4 vertebrae (mg/cm3) was measured in by QCT (Philips Brilliance 16). FF in the same area was measured from 1H-MR-spectra (STEAM, echo time (TE)=12.8 ms, repetition time (TR)=3000 ms, voxel size=20×15×10 mm) using Philips Achieva TX 3.0T MRI scanner.Results: Correlation analysis revealed a significant inverse linear correlation (r=-0.55, p=0.0004) between FF and BMD of L3 и L4 vertebrae. In addition, in the patients with severe compression vertebral fracture (more than 2 fractured vertebrae) there was a significant increase in FF values and a BMD decrease, compared to the values in the patients with mild fractures (1–2 fractured vertebrae).Conclusion: The correlation suggests that the increase of FF in the bone marrow and the decrease of BMD in children go in parallel. Therefore, 1H-MRS could be an alternative to QCT and dual-energy X-ray absorptiometry. The absence of radiation load allows for recommendation to use 1Н-MRS for screening and follow-up, as well as for the control of BMD.

Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons.

Diabetes predisposes to cognitive decline leading to dementia and is associated with decreased brain NAD+ levels. This has triggered an intense interest in boosting nicotinamide adenine dinucleotide (NAD+) levels to prevent dementia. We tested if the administration of the precursor of NAD+, nicotinamide mononucleotide (NMN), can prevent diabetes-induced memory deficits. Diabetes was induced in Sprague-Dawley rats by the administration of streptozotocin (STZ). After 3 months of diabetes, hippocampal NAD+ levels were decreased (p = 0.011). In vivo localized high-resolution proton magnetic resonance spectroscopy (MRS) of the hippocampus showed an increase in the levels of glucose (p < 0.001), glutamate (p < 0.001), gamma aminobutyric acid (p = 0.018), myo-inositol (p = 0.018), and taurine (p < 0.001) and decreased levels of N-acetyl aspartate (p = 0.002) and glutathione (p < 0.001). There was a significant decrease in hippocampal CA1 neuronal volume (p < 0.001) and neuronal number (p < 0.001) in the Diabetic rats. Diabetic rats showed hippocampal related memory deficits. Intraperitoneal NMN (100 mg/kg) was given after induction and confirmation of diabetes and was provided on alternate days for 3 months. NMN increased brain NAD+ levels, normalized the levels of glutamate, taurine, N-acetyl aspartate (NAA), and glutathione. NMN-treatment prevented the loss of CA1 neurons and rescued the memory deficits despite having no significant effect on hyperglycemic or lipidemic control. In hippocampal protein extracts from Diabetic rats, SIRT1 and PGC-1α protein levels were decreased, and acetylation of proteins increased. NMN treatment prevented the diabetes-induced decrease in both SIRT1 and PGC-1α and promoted deacetylation of proteins. Our results indicate that NMN increased brain NAD+, activated the SIRT1 pathway, preserved mitochondrial oxidative phosphorylation (OXPHOS) function, prevented neuronal loss, and preserved cognition in Diabetic rats.

Invivo MR spectroscopy predicts high tumor grade in endometrial cancer.

Background Invivo magnetic resonance spectroscopy (MRS) enables non-invasive measurements of tumor metabolites. Choline-containing metabolites play a key role in tumor metabolism. Purpose To explore whether preoperative MRS-derived tumor choline levels are associated with clinical and histological features in endometrial carcinomas. Material and Methods Preoperative pelvic magnetic resonance imaging (MRI) (1.5T), including structural and diffusion-weighted imaging and localized multivoxel proton MR (1H-MR) spectroscopy, was performed in 77 prospectively included patients with histologically confirmed endometrial carcinomas. Relative levels of total choline-containing metabolites (tCho) in tumor and myometrium were measured using the ratios: tCho/Creatine; tCho/Water; and tCho/Noise. MRS parameters were analyzed in relation to histological subtype and grade, surgicopathological staging parameters, MRI-measured tumor volume, and tumor apparent diffusion coefficient (ADC) value and clinical outcome. Results Tumor tissue had significantly higher ratios for tCho/Creatine, tCho/Water, and tCho/Noise than normal myometrial tissue ( P < 0.001 for all). High tumor tCho/Water ratio was significantly associated with high tumor grade in endometrioid tumors ( P = 0.02). Tumor tCho/Creatine ratio was positively correlated to MRI-measured tumor volume (rs = 0.25; P = 0.03). Conclusion High choline levels in tumor are associated with high-risk features. Invivo MRS may potentially aid in the preoperative risk stratification in endometrial cancer.

Fully navigated 3 T proton magnetic resonance spectroscopy of liver metastases with inner-volume saturation.

To demonstrate that fully navigated magnetic resonance spectroscopy (MRS) with inner-volume saturation (IVS) at 3 T results in high-quality spectra that permit evaluating metabolic changes in hepatic metastases without the need for patient compliance. Nine patients with untreated, biopsy-proven large hepatic metastases (minimum diameter of 3cm) were included. In each patient, localized proton MRS was performed in the metastatic lesion and in uninvolved liver parenchyma. To improve quality and consistency of proton MRS, navigator gating was thereby performed not only during acquisition of the spectroscopic data but also during localization imaging and throughout the preparation phases. IVS was utilized to reduce chemical shift displacement between different metabolites and to diminish flow artifacts. Metabolite quantities were normalized relative to the unsuppressed water peak and choline-containing compounds (CCC) to lipid ratios were determined. Wilcoxon signed-rank tests were used to assess differences in the amounts of lipids and CCC as well as the CCC-to-lipid ratios between liver metastases and normal-appearing liver parenchyma. Fully navigated point-resolved spectroscopy with IVS resulted in high-quality spectra in all patients. Navigator gating during localization imaging and spectroscopic acquisition thereby ensured a precise localization of the spectroscopic voxel. Decreased quantities of lipid and CCC were observed in metastatic tissue compared with uninvolved liver parenchyma. However, the latter trend fell short of statistical significance. Moreover, elevated levels of the CCC-to-lipid ratios were detected in metastatic tissue relative to normal-appearing liver parenchyma. The present study demonstrates that fully navigated MRS of the liver with IVS at 3 T allows for a precise localization of the spectroscopic voxel and results in high-quality spectra that permit evaluating liver metabolism without the need for patient compliance.

A practical guide to in vivo proton magnetic resonance spectroscopy at high magnetic fields

Localized proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive tool for measuring in vivo neurochemical information in animal and human brains. With the increase of magnetic field strength, whereas localized 1H-MRS benefits from higher sensitivity and spectral dispersion, it is challenged by increased spatial inhomogeneity of the B0 and B1 fields, larger chemical shift displacement error, and shortened T2 relaxation times of metabolites. Advanced localized 1H-MRS methodologies developed for high magnetic fields have shown promising results and allow the measurement of neurochemical profiles with up to 19 brain metabolites, including less-abundant metabolites, such as glutathione, glycine, γ-aminobutyric acid and ascorbate. To provide a practical guide for conducting in vivo1H-MRS studies at high magnetic field strength, we reviewed various essential technical aspects from data acquisition (hardware requirements, B1 and B0 inhomogeneity, water suppression, localization sequences and acquisition strategies) to data processing (frequency and phase correction, spectral quality control, spectral fitting and concentration referencing). Additionally, we proposed guidelines for choosing the most appropriate data acquisition and processing approaches to maximize the achievable neurochemical information.

Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1 T.

Glioma models have provided important insights into human brain cancers. Among the investigative tools, MRI has allowed their characterization and diagnosis. In this study, we investigated whether diffusion MRI might be a useful technique for early detection and characterization of slow-growing and diffuse infiltrative gliomas, such as the proposed new models, LN-2669GS and LN-2540GS glioma sphere xenografts. Tumours grown in these models are not visible in conventional T2 -weighted or contrast-enhanced T1 -weighted MRI at 14.1 T. Diffusion-weighted imaging and diffusion tensor imaging protocols were optimized for contrast by exploring long diffusion times sensitive for probing the microstructural alterations induced in the normal brain by the slow infiltration of glioma sphere cells. Compared with T2 -weighted images, tumours were properly identified in their early stage of growth using diffusion MRI, and confirmed by localized proton MR spectroscopy as well as immunohistochemistry. The first evidence of tumour presence was revealed for both glioma sphere xenograft models three months after tumour implantation, while no necrosis, oedema or haemorrhage were detected either by MRI or by histology. Moreover, different values of diffusion indices, such as mean diffusivity and fractional anisotropy, were obtained in tumours grown from LN-2669GS and LN-2540GS glioma sphere lines. These observations highlighted diverse tumour microstructures for both xenograft models, which were reflected in histology. This study demonstrates the ability of diffusion MRI techniques to identify and investigate early stages of slow-growing, invasive tumours in the mouse brain, thus providing a potential imaging biomarker for early detection of tumours in humans.

Peak joint angular velocities of the straight punch in professional boxers

Localized proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive tool for measuring in vivo neurochemical information in animal and human brains. With the increase of magnetic field strength, whereas localized 1H-MRS benefits from higher sensitivity and spectral dispersion, it is challenged by increased spatial inhomogeneity of the B0 and B1 fields, larger chemical shift displacement error, and shortened T2 relaxation times of metabolites. Advanced localized 1H-MRS methodologies developed for high magnetic fields have shown promising results and allow the measurement of neurochemical profiles with up to 19 brain metabolites, including less-abundant metabolites, such as glutathione, glycine, γ-aminobutyric acid and ascorbate. To provide a practical guide for conducting in vivo 1H-MRS studies at high magnetic field strength, we reviewed various essential technical aspects from data acquisition (hardware requirements, B1 and B0 inhomogeneity, water suppression, localization sequences and acquisition strategies) to data processing (frequency and phase correction, spectral quality control, spectral fitting and concentration referencing). Additionally, we proposed guidelines for choosing the most appropriate data acquisition and processing approaches to maximize the achievable neurochemical information.

Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice.

Adolescence is the critical time for developing proper oligodendrocyte (OL)-neuron interaction and the peak of onset for many cognitive diseases, among which anxiety disorders display the highest prevalence. However, whether impairment of de novo OL development causes neuronal abnormalities and contributes to the early onset of anxiety phenotype in childhood still remains unexplored. In this study, we tested the hypothesis that defects in OL maturation manifests cortical neuron function and leads to anxiety-like behaviors in juvenile mice. We report here that conditional knockout of the Olig2 gene (Olig2 cKO) specifically in differentiating OLs in the mouse brain preferentially impaired OL maturation in the gray matter of cerebral cortex. Interestingly, localized proton magnetic resonance spectroscopy revealed that Olig2 cKO mice displayed abnormally elevated cortical glutamate levels. In addition, transmission electron microscopy demonstrated increased vesicle density in excitatory glutamatergic synapses in the cortex of the Olig2 cKO mice. Moreover, juvenile Olig2 cKO mice exhibited anxiety-like behaviors and impairment in behavioral inhibition. Taken together, our results suggest that impaired OL development affects glutamatergic neuron function in the cortex and causes anxiety-related behaviors in juvenile mice. These discoveries raise an intriguing possibility that OL defects may be a contributing mechanism for the onset of anxiety in childhood.

Longitudinal monitoring of metabolic alterations in cuprizone mouse model of multiple sclerosis using 1H-magnetic resonance spectroscopy

Non-invasive measures of well-known pathological hallmarks of multiple sclerosis (MS) such as demyelination, inflammation and axonal injury would serve as useful markers to monitor disease progression and evaluate potential therapies. To this end, in vivo localized proton magnetic resonance spectroscopy (1H-MRS) provides a powerful means to monitor metabolic changes in the brain and may be sensitive to these pathological hallmarks. In our study, we used the cuprizone mouse model to study pathological features of MS, such as inflammation, de- and remyelination, in a highly reproducible manner. C57BL/6J mice were challenged with a 0.2% cuprizone diet for 6-weeks to induce demyelination, thereafter the mice were put on a cuprizone free diet for another 6weeks to induce spontaneous remyelination. We employed in vivo 1H-MRS to longitudinally monitor metabolic changes in the corpus callosum of cuprizone-fed mice during the demyelination (weeks 4 and 6) and spontaneous remyelination (week 12) phases. The MRS spectra were quantified with LCModel and since the total creatine (tCr) levels did not change over time or between groups, metabolite concentrations were expressed as ratios relative to tCr. After 4 and 6weeks of cuprizone treatment a significant increase in taurine/tCr and a significant reduction in total N-acetylaspartate/tCr, total choline-containing compounds/tCr and glutamate/tCr could be observed compared to mice under normal diet. At week 12, when almost full remyelination was established, no statistically significant metabolic differences were present between the control and cuprizone group. Our results suggest that these metabolic changes may represent sensitive markers for cuprizone induced demyelination, axonal injury and inflammation. To the best of our knowledge, this is the first longitudinal in vivo 1H-MRS study that monitored biochemical changes in the corpus callosum of cuprizone fed mice.

Neuronal marker recovery after Simvastatin treatment in dementia in the rat brain: In vivo magnetic resonance study

The aim of study was to search for new biomarkers with a magnetic resonance technique to identify the early stages of dementia, induced by d-galactose, and evaluate Simvastatin therapy. Localized proton magnetic resonance spectroscopy measurements showed a significant decrease in the concentration of N-acetylaspartate+N-acetylaspartylglutamate and myo-inositol in the d-galactose group compared to the control group, and, conversely, an increase of N-acetylaspartate+N-acetylaspartylglutamate in the d-galactose/Simvastatin group. Using a saturation transfer experiment, with phosphorus magnetic resonance spectroscopy, we observed a significant elevation of the forward rate constant of the creatine kinase reaction in the brains of the d-galactose group compared to controls, and subsequently, a significant reduction of this reaction in the d-galactose/Simvastatin group. Spatial learning and memory were evaluated using the modified Morris water maze test. The dynamics of the learning process represented by the learning index revealed a significant reduction in learning in the d-galactose group, but the deficits as a consequence of the d-galactose effects were recovered in the d-galactose/Simvastatin group, in which the learning dynamics resembled those of the control group. By determining the thiobarbituric acid reactive substances and total coenzyme Q9 in plasma, we have shown that long-term administration of d-galactose created conditions for oxidative stress, and that the administration of Simvastatin decreased oxidative stress in plasma. Volumetry analyses from the hippocampal area show a reduction in the segmented area in the d-galactose group, compared with the control group, and an enlarged area in the hippocampus in the d-galactose/Simvastatin group.

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

BackgroundA disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain.Methods/DesignYoung adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus.DiscussionWe will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.

Examining cerebral metabolic abnormalities in chronic obstructive pulmonary disease (COPD) patients by localized proton magnetic resonance spectroscopy (MRS).

The study was planned based on the hypothesis that cerebral metabolism is impaired in chronic obstructive pulmonary disease (COPD) by using localized in vivo proton magnetic resonance spectroscopy. The study comprised 30 male patients, aged 45-70 years, with moderate level COPD and an aged matched group of 30 healthy males as the control group. Cerebral metabolism was investigated with proton magnetic resonance spectroscopy (MRS) using multivoxel technique. Data normal distribution conformity was evaluated by the One Sample Kolmogorov Smirnov Test and homogeneity by the One-Way ANOVA test. For both the COPD and control group, data were obtained as mean, standard deviations, minimum and maximum values. Independent sample t-test was used for the comparison of means between the two groups. The frontal and parietal white matter in patients with COPD showed an overall reduction in cerebral metabolites. The NAA (N-acetylaspartate)/Cr (Creatinine), Cho (Choline)/Cr ratios of the cerebral frontal and parietal white matter regions in the COPD group were significantly lower than the control group. The findings of this study through the use of MRS confirmed that most patients with symptomatic COPD have cerebral metabolic abnormalities.

Halogenated volatile anesthetics alter brain metabolism as revealed by proton magnetic resonance spectroscopy of mice in vivo

Halogenated volatile anesthetics (HVA) are widely used in medicine and research but their effects on brain metabolism in intact organisms are still largely unknown. Here, localized proton magnetic resonance spectroscopy (MRS) of anesthetized mice was applied to evaluate HVA effects on cerebral metabolites in vivo. Experimental protocols combined different concentrations of isoflurane, halothane, sevoflurane, and desflurane with known modulators of adrenergic, GABAergic, and glutamatergic neurotransmission. As a most striking finding, brain lactate increased in individual mice from 1.0 ± 0.6 mM (awake state) to 6.2 ± 1.5 mM (1.75% isoflurane). In addition, relative to total creatine, there were significant isoflurane-induced increases of alanine by 111%, GABA by 20%, choline-containing compounds by 20%, and myo-inositol by 10% which were accompanied by significant decreases of glucose by 51% and phosphocreatine by 9%. The elevation of lactate was most pronounced in the striatum. The HVA effects correlated with the respective minimal alveolar concentrations and were mostly reversible within minutes. The observed alterations are best explained by an HVA-induced stimulation of adrenergic pathways in conjunction with an inhibition of the respiratory chain. Apart from casting new light on cerebral energy metabolism, the present results challenge brain studies of HVA-anesthetized animals.

Handling Macromolecule Signals in the Quantification of the Neurochemical Profile

In vivo localized proton magnetic resonance spectroscopy (1H MRS) became a powerful and unique technique to non-invasively investigate brain metabolism of rodents and humans. The main goal of 1H MRS is the reliable quantification of concentrations of metabolites (neurochemical profile) in a well-defined region of the brain. The availability of very high magnetic field strengths combined with the possibility of acquiring spectra at very short echo time have dramatically increased the number of constituents of the neurochemical profile. The quantification of spectra measured at short echo times is complicated by the presence of macromolecule signals of particular importance at high magnetic fields. An error in the macromolecule estimation can lead to substantial errors in the obtained neurochemical profile. The purpose of the present review is to overview methods of high field 1H MRS with a focus on the metabolite quantification, in particular in handling signals of macromolecules. Three main approaches of handling signals of macromolecules are described, namely mathematical estimation of macromolecules, measurement of macromolecules in vivo, and direct acquisition of the in vivo spectrum without the contribution of macromolecules.

The Impact of Gabapentin Administration on Brain GABA and Glutamate Concentrations: A 7T 1H-MRS Study

Gamma-aminobutyric acid (GABA) and glutamate are implicated in numerous neuropsychiatric and substance abuse conditions, but their spectral overlap with other resonances makes them a challenge to quantify in humans. Gabapentin, marketed for the treatment of seizures and neuropathic pain, has been shown to increase in vivo GABA concentration in the brain of both rodents and humans. Gabapentin effects on glutamate are not known. We conducted a gabapentin (900 mg) challenge in healthy human subjects to confirm and explore its effects on GABA and glutamate concentrations, respectively, and to test the ability of single voxel localized proton magnetic resonance spectroscopy (¹H-MRS) to reliably measure GABA and glutamate in the visual cortex at the ultra-high magnetic field of 7 Tesla. Reproducibility of GABA and glutamate measurements was determined in a comparison group without drug twice within day and 2 weeks apart. Although GABA concentration changes were small both within day (average 5.6%) and between day (average 4.8%), gabapentin administration was associated with an average increase in GABA concentration of 55.7% (6.9-91.0%). Importantly, drug-induced change in GABA levels was inversely correlated to the individual's baseline GABA level (R²=0.72). Mean glutamate concentrations did not change significantly with or without drug administration. In conclusion, localized ¹H-MRS at 7 Tesla can be successfully applied to the measurement of GABA concentration and is sensitive to acute drug-induced changes in cortical GABA. Whether baseline GABA concentrations predict clinical efficacy of gabapentin is an area worthy of exploration.

A rare inborn error of metabolism associated with a Dandy–Walker malformation

A baby girl, born to second-degree consanguineously married couple, was delivered by forceps, after a full-term pregnancy. Apgar scores were 9 and 10, birth weight 4,100 g, and head circumference 35 cm. The baby was hospitalized, at the age of 20 days, for recurrent myoclonic seizures. Physical examination found hypotonia and absent reflexes. Amino acid analysis of the cerebrospinal fluid (CSF) and plasma was performed, to exclude the possibility of metabolic disorder. A brain ultrasonography found hypoplastic corpus callosum. An expansion of the cisterna magna communicating with the fourth ventricle and a cerebellar vermis hypoplasia were also showed. These findings, suggested a Dandy–Walker malformation. 1 day later, brain magnetic resonance (MR) imaging and spectroscopy were performed. MRI confirmed the brain ultrasonography findings (Fig. 1). On the T1and T2-weighted images, the appearance of the white matter myelination was inappropriate for age. The axial T2-weighted images revealed increased signal intensity in the dorsal brain stem, the middle cerebellar peduncles, and the posterior limbs of the internal capsules. Diffusion-weighted MR images found hyperintense signal intensity in these areas, in combination with low apparent diffusion coefficient (ADC) values, consistent with restricted diffusion (Fig. 2). Localized proton MR spectroscopy showed a markedly increased peak intensity at 3.55 ppm, which was assigned to glycine and a lactate peak at 1.33 ppm (Fig. 3). The diagnosis of nonketotic hyperglycinemia (NKH) was made by laboratory findings of elevated CSF and plasma glycine levels, which were 250 lmol/L (normal range 1–15 lmol/L) and 1,540 lmol/L (normal range 230–740 lmol/L), respectively. The CSF-to-plasma glycine ratio was also elevated to 0.16 (normal range 0.02–0.03). 4 days later, the baby became lethargic, and the shallow respiration which began at that point progressed to intermittent apnea, requiring mechanical ventilation. 1 day later the infant died.

In vivo short TE localized 1H MR spectroscopy of mouse cervical spinal cord at very high magnetic field (11.75 T)

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.

Hepatic lipid composition differs between ob/ob and ob/+ control mice as determined by using in vivo localized proton magnetic resonance spectroscopy

Hepatic lipid accumulation is associated with nonalcoholic fatty liver disease, and the metabolic syndrome constitutes an increasing medical problem. In vivo proton magnetic resonance spectroscopy ((1)H MRS) allows the assessment of hepatic lipid levels noninvasively and also yields information on the fat composition due to its high spectral resolution. We applied (1)H MRS at 9.4T to study lipid content and composition in eight leptin-deficient ob/ob mice as a model of obesity and in four lean ob/+ control mice at 24 weeks of age. PRESS sequence was used. For accurate estimation of signal intensity, differences in relaxation behavior of individual signals were accounted for each mouse individually. Also, in order to minimize spectral degrading due to motion artifacts, respiration gating was applied. Significant differences between ob/ob and ob/+ control mice were found in both lipid content and composition. The mean chain length was found to be significantly longer in ob/ob mice with a higher fraction of monounsaturated lipids. (1)H MRS enables accurate assessment in hepatic lipids in mice, which is attractive for mechanistic studies of altered metabolism given the large number of genetically engineered mouse models available.