Localized in vivo 13C-NMR of glutamate metabolism in the human brain: Initial results at 4 Tesla

Using optimized administration of 13C-labeled glucose, the time course of the specific activity of glucose was measured directly by in vivo 13C-NMR in the human brain at 4 Tesla. Subsequent label incorporation was measured at the C2, C3 and C4 positions of both glutamate and the well-resolved C2, C3 and C4 resonances of glutamine and at the C2 and C3 positions of aspartate. GABA was clearly observed for the first time in vivo, suggesting a substantial GABA turnover in the normal human visual cortex. Likewise, lactate C3 labeled with an estimated active pool size on the order of 0.5 mM. A model of cerebral glutamate metabolism is proposed which predicts that glutamatergic action ('neurotransmission'), pyruvate carboxylase flux, TCA cycle activity, glucose consumption and exchange across the mitochondrial membrane can be assessed simultaneously in the human brain

Noninvasive measurements of [1-13C]glycogen concentrations and metabolism in rat brain in vivo

Using a specific 13C NMR localization method, 13C label incorporation into the glycogen C1 resonance was measured while infusing [1- 13C]glucose in intact rats. The maximal concentration of [1-13C]glycogen was 5.1 ± 0.6 μmol g-1 (mean ± SE, n = 8). During the first 60 rain of acute hyperglycemia, the rate of 13C label incorporation (synthase flux) was 2.3 ± 0.7 μmol g-1 h-1 (mean ± SE, n = 9 rats), which was higher (p 0.05 for correlation). The results implied that net glycogen synthesis of ~3 μmol g-1 had occurred, similar to previous reports. When infusing unlabeled glucose before [1-13C]glucose in three studies, the rate of glycogen C1 accumulation was 0.46 ± 0.08 μmol g-1 h-1. The results suggest that steady-state glycogen turnover rates during hyperglycemia are ~1% of glucose consumption

In vivo 1H NMR spectroscopy of the human brain at high magnetic fields: Metabolite quantification at 4T vs. 7T

A comprehensive comparative study of metabolite quantification from the human brain was performed on the same 10 subjects at 4T and 7T using MR scanners with identical consoles, the same type of RF coils, and identical pulse sequences and data analysis. Signal-to-noise ratio (SNR) was increased by a factor of 2 at 7T relative to 4T in a volume of interest selected in the occipital cortex using half-volume quadrature radio frequency (RF) coils. Spectral linewidth was increased by 50% at 7T, which resulted in a 14% increase in spectral resolution at 7T relative to 4T. Seventeen brain metabolites were reliably quantified at both field strengths. Metabolite quantification at 7T was less sensitive to reduced SNR than at 4T. The precision of metabolite quantification and detectability of weakly represented metabolites were substantially increased at 7T relative to 4T. Because of the increased spectral resolution at 7T, only one-half of the SNR of a 4T spectrum was required to obtain the same quantification precision. The Cramé r-Rao lower bounds (CRLB), a measure of quantification precision, of several metabolites were lower at both field strengths than the intersubject variation in metabolite concentrations, which resulted in a strong correlation between metabolite concentrations of individual subjects measured at 4T and 7T. © 2009 Wiley-Liss, Inc

Proton-observed carbon-edited NMR spectroscopy in strongly coupled second-order spin systems

Proton-observed carbon-edited (POCE) NMR spectroscopy is commonly used to measure 13C labeling with higher sensitivity compared to direct 13C NMR spectroscopy, at the expense of spectral resolution. For weakly coupled first-order spin systems, the multiplet signal at a specific proton chemical shift in POCE spectra directly reflects 13C enrichment of the carbon attached to this proton. The present study demonstrates that this is not necessarily the case for strongly coupled second-order spin systems. In such cases NMR signals can be detected in the POCE spectra even at chemical shifts corresponding to protons bound to 12C. This effect is demonstrated theoretically with density matrix calculations and simulations, and experimentally with measured POCE spectra of [3-13C] glutamate. © 2003 Wiley-Liss, Inc

Sustained neuronal activation raises oxidative metabolism to a new steady-state level: Evidence from 1H NMR spectroscopy in the human visual cortex

To date, functional 1H NMR spectroscopy has been utilized to report the time courses of few metabolites, primarily lactate. Benefiting from the sensitivity offered by ultra-high magnetic field (7 T), the concentrations of 17 metabolites were measured in the human visual cortex during two paradigms of visual stimulation lasting 5.3 and 10.6 mins. Significant concentration changes of approximately 0.2 μmol/g were observed for several metabolites: lactate increased by 23%±5% (P<0.0005), glutamate increased by 3%±1% (P<0.01), whereas aspartate decreased by 15%±6% (P<0.05). Glucose concentration also manifested a tendency to decrease during activation periods. The lactate concentration reached the new steady-state level within the first minute of activation and came back to baseline only after the stimulus ended. The changes of the concentration of metabolites implied a rise in oxidative metabolism to a new steady-state level during activation and indicated that amino-acid homeostasis is affected by physiological stimulation, likely because of an increased flux through the malate-aspartate shuttle. © 2007 ISCBFM All rights reserved

Magnetic resonance studies of brain function and neurochemistry

In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves

Multimodal population brain imaging in the UK Biobank prospective epidemiological study

Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, with health outcomes being tracked over the coming decades. The brain imaging includes structural, diffusion and functional modalities. Along with body and cardiac imaging, genetics, lifestyle measures, biological phenotyping and health records, this imaging is expected to enable discovery of imaging markers of a broad range of diseases at their earliest stages, as well as provide unique insight into disease mechanisms. We describe UK Biobank brain imaging and present results derived from the first 5,000 participants' data release. Although this covers just 5% of the ultimate cohort, it has already yielded a rich range of associations between brain imaging and other measures collected by UK Biobank

The nature of spatiotemporal changes in cerebral hemodynamics as manifested in functional magnetic resonance imaging

The nature of changes in rapidly acquired magnetic resonance images of the brain was studied by using a denoising method and spectral techniques optimally suited to short time series. It was found that the stimulus related changes have a complex epatiotemporal structure even for simple visual stimuli. Apart from a low frequency window, the non-stimulus-related changes were found to correspond in detail to either breathing or heartbeat, although these two sources show different patterns of spatial coherence in the image. At low frequencies, oscillations with frequencies around 0.1 Hz were observed, also with nontrivial space-time structure, which are likely to be vasomotor in origin