Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26 ± 0.06 μmol/g (~30%) and 0.28 ± 0.03 μmol/g (~3%), respectively, while aspartate and glucose decreased by 0.20 ± 0.04 μmol/g (~5%) and 0.19 ± 0.03 μmol/g (~16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms. Journal of Cerebral Blood INTRODUCTIONFunctional magnetic resonance spectroscopy (fMRS) is a powerful tool that allows quantifying the dynamic of brain metabolite concentrations in the working brain in vivo. Different laboratories have recently used fMRS at ultra-high magnetic field (7 Tesla (7 T)) to measure the neurochemical responses occurring during stimulation of the human visual cortex. [1][2][3][4] The results of these studies were highly consistent with concentration changes in the order of 0.2 μmol/g being reported for aspartate (Asp), glutamate (Glu), glucose (Glc), and lactate (Lac) during prolonged visual stimuli. Similar changes of Glu and Lac have also been reported in the motor cortex. 5 The observed functional changes of metabolite concentrations support an overall increase in oxidative energy metabolism during neuronal activation. 6 In particular, the opposite changes in Glc and Lac concentrations are thought to reflect increased metabolic rate of Glc utilization and activation of the aerobic glycolytic pathway in brain cells. [7][8][9] The observed decrease in Asp and increase in Glu have been interpreted as a consequence of an increased rate of the malate-aspartate shuttle, which is associated with the increased flux into the tricarboxylic acid (TCA) cycle.

Purpose To determine the test-retest reproducibility of neurochemical concentrations obtained with a highly optimized, short-echo, single voxel proton MRS pulse sequence at 3T and 7T using state-of-the-art hardware. Methods A semi-LASER sequence (TE = 26–28ms) was used to acquire spectra from the posterior cingulate and cerebellum at 3T and 7T from 6 healthy volunteers who were scanned weekly 4 times on both scanners. Spectra were quantified with LCModel. Results More neurochemicals were quantified with mean Cramér-Rao lower bounds (CRLB) ≤ 20% at 7T than at 3T despite comparable frequency-domain SNR. While CRLB were lower at 7T (p < 0.05), between-session coefficients of variance (CVs) were comparable at the two fields with 64 transients. Five metabolites were quantified with between-session CVs ≤ 5% at both fields. Analysis of subspectra showed that a minimum achievable CV was reached with a lower number of transients at 7T for multiple metabolites and that between-session CVs were lower at 7T than at 3T with fewer than 64 transients. Conclusion State-of-the-art MRS methodology allows excellent reproducibility for many metabolites with 5 minute data averaging on clinical 3T hardware. Sensitivity and resolution advantages at 7T are important for weakly represented metabolites, short acquisitions and small volumes-of-interest.

In the present study, we aimed at determining the metabolic responses of the human visual cortex during the presentation of chromatic and achromatic stimuli, known to preferentially activate two separate clusters of neuronal populations (called "blobs" and "interblobs") with distinct sensitivity to color or luminance features. Since blobs and interblobs have different cytochrome-oxidase (COX) content and micro-vascularization level (i.e., different capacities for glucose oxidation), different functional metabolic responses during chromatic vs. achromatic stimuli may be expected. The stimuli were optimized to evoke a similar load of neuronal activation as measured by the bold oxygenation level dependent (BOLD) contrast. Metabolic responses were assessed using functional H MRS at 7 T in 12 subjects. During both chromatic and achromatic stimuli, we observed the typical increases in glutamate and lactate concentration, and decreases in aspartate and glucose concentration, that are indicative of increased glucose oxidation. However, within the detection sensitivity limits, we did not observe any difference between metabolic responses elicited by chromatic and achromatic stimuli. We conclude that the higher energy demands of activated blobs and interblobs are supported by similar increases in oxidative metabolism despite the different capacities of these neuronal populations.

summary Hippocampal dysfunction is known to be associated with several neurological and neuropsychiatric disorders such as Alzheimer's disease, epilepsy, schizophrenia and depression, therefore there has been significant clinical interest to study hippocampal neurochemistry. However the hippocampus is a challenging region to study using 1H MRS, hence the use of MRS for clinical research in this region has been limited. Therefore, our goal was to investigate the feasibility of obtaining high quality hippocampal spectra that allow reliable quantification of a neurochemical profile and to establish inter-session reproducibility of hippocampal MRS, including reproducibility of voxel placement, spectral quality and neurochemical concentrations. Ten healthy volunteers were scanned in two consequent sessions using a standard clinical 3T MR scanner. Neurochemical profiles were obtained with a short-echo (TE=28ms) semi-LASER localization sequence from a relatively small (~4mL) voxel that covered ~62% of the hippocampal volume as calculated from segmentation of T1-weighted images. Voxel composition was highly reproducible between sessions, with test-retest coefficients-of-variance (CV) of 3.5% and 7.5% for gray and white matter volume fraction, respectively. Excellent signal-to-noise ratio (~54 based on the N-acetylaspartate (NAA)-methyl peak in non-apodized spectra) and linewidths (~9 Hz for water) were achieved reproducibly in all subjects. The spectral quality allowed quantification of NAA, total choline, total creatine, myo-inositol and glutamate with high scan-rescan reproducibility (CV ≤ 6%) and quantification precision (Cramér-Rao lower bounds, CRLB < 9%). Four other metabolites, including glutathione and glucose, were quantified with scan-rescan CV below 20%. Therefore, the highly optimized, short echo semi-LASER sequence together with FASTMAP shimming substantially improved the reproducibility and number of quantifiable metabolites relative to prior reports. In addition, the between-session variation in metabolite concentrations, as well as CRLB were lower than between-subject variation of the concentrations for most metabolites indicating that the method has the sensitivity to detect inter-individual differences in the healthy brain.

Background and purpose Non‐myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract‐specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM. Methods High‐resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract‐specific diffusion metrics and corresponding electrophysiological measures and compression severity. Relationship between the degree of DCM disability, assessed by the modified Japanese Orthopaedic Association scale, and tract‐specific microstructural changes in DCM patients was also explored. Results The study identified diffusion‐derived abnormalities in the gray matter, dorsal and lateral tracts congruent with trans‐synaptic degeneration and demyelination in chronic degenerative spinal cord compression with more profound alterations in DCM than NMDC. Diffusion metrics were affected in the C3‐6 area as well as above the compression level at C3 with more profound rostral deficits in DCM than NMDC. Alterations in lateral motor and dorsal sensory tracts correlated with motor and sensory evoked potentials, respectively, whereas electromyography outcomes corresponded with gray matter microstructure. DCM disability corresponded with microstructure alteration in lateral columns. Conclusions Outcomes imply the necessity of high‐resolution tract‐specific diffusion MRI for monitoring degenerative spinal pathology in longitudinal studies.

Diffusion magnetic resonance imaging (dMRI) proved promising in patients with non-myelopathic degenerative cervical cord compression (NMDCCC), i.e., without clinically manifested myelopathy. Aim of the study is to present a fast multi-shell HARDI-ZOOMit dMRI protocol and validate its usability to detect microstructural myelopathy in NMDCCC patients. In 7 young healthy volunteers, 13 age-comparable healthy controls, 18 patients with mild NMDCCC and 15 patients with severe NMDCCC, the protocol provided higher signal-to-noise ratio, enhanced visualization of white/gray matter structures in microstructural maps, improved dMRI metric reproducibility, preserved sensitivity (SE = 87.88%) and increased specificity (SP = 92.31%) of control-patient group differences when compared to DTI-RESOLVE protocol (SE = 87.88%, SP = 76.92%). Of the 56 tested microstructural parameters, HARDI-ZOOMit yielded significant patient-control differences in 19 parameters, whereas in DTI-RESOLVE data, differences were observed in 10 parameters, with mostly lower robustness. Novel marker the white-gray matter diffusivity gradient demonstrated the highest separation. HARDI-ZOOMit protocol detected larger number of crossing fibers (5–15% of voxels) with physiologically plausible orientations than DTI-RESOLVE protocol (0–8% of voxels). Crossings were detected in areas of dorsal horns and anterior white commissure. HARDI-ZOOMit protocol proved to be a sensitive and practical tool for clinical quantitative spinal cord imaging.

In this study, we retrospectively analyzed the anatomical MRI data acquired from 52 subjects with type 1 diabetes (26M/26F, 36 ± 11 years old, A1C = 7.2 ± 0.9%) and 50 age, sex and BMI frequency-matched non-diabetic controls (25M/25F, 36 ± 14 years old). The T1D group was further sub-divided based on whether subjects had normal, impaired, or indeterminate awareness of hypoglycemia (n = 31, 20, and 1, respectively). Our goals were to test whether the gray matter (GM) volumes of selected brain regions were associated with diabetes status as well as with the status of hypoglycemia awareness. T1D subjects were found to have slightly smaller volume of the whole cortex as compared to controls (−2.7%, p = 0.016), with the most affected brain region being the frontal lobe (−3.6%, p = 0.024). Similar differences of even larger magnitude were observed among the T1D subjects based on their hypoglycemia awareness status. Indeed, compared to the patients with normal awareness of hypoglycemia, patients with impaired awareness had smaller volume of the whole cortex (−7.9%, p = 0.0009), and in particular of the frontal lobe (−9.1%, p = 0.006), parietal lobe (−8.0%, p = 0.015) and temporal lobe (−8.2%, p = 0.009). Such differences were very similar to those observed between patients with impaired awareness and controls (−7.6%, p = 0.0002 in whole cortex, −9.1%, p = 0.0003 in frontal lobe, −7.8%, p = 0.002 in parietal lobe, and −6.4%, p = 0.019 in temporal lobe). On the other hand, patients with normal awareness did not present significant volume differences compared to controls. No group-differences were observed in the occipital lobe or in the anterior cingulate, posterior cingulate, hippocampus, and thalamus. We conclude that diabetes status is associated with a small but statistically significant reduction of the whole cortex volume, mainly in the frontal lobe. The most prominent structural effects occurred in patients with impaired awareness of hypoglycemia (IAH) as compared to those with normal awareness, perhaps due to the long-term exposure to recurrent episodes of hypoglycemia. Future studies aimed at quantifying relationships of structural outcomes with functional outcomes, with cognitive performance, as well as with parameters describing glucose variability and severity of hypoglycemia episodes, will be necessary to further understand the impact of T1D on the brain.

Furthermore, no statistically significant associations between changes in any of the neurotransmitter ratios and plasma levels of ketamine, norketamine, or dehydronorketamine were observed (p corr > 0.05). Conclusion: This study provides evidence for decreased hippocampal GABA+/tCr ratio 2 h following ketamine administration. As MRS methodology measures total levels of intraand extracellular GABA, results might indicate drug induced alterations in GABA turnover. Our study in healthy humans suggests that changes in GABA levels, particularly in the hippocampus, should be further assessed for their relevance to ketamine´s antidepressant effects.