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Supplemental material, JCB910535 Supplemental Material for Excitatory/inhibitory neuronal metabolic balance in mouse hippocampus upon infusion of [U-13C6]glucose by Antoine Cherix, Guillaume Donati, Blanca Lizarbe, Bernard Lanz, Carole Poitry-Yamate, Hongxia Lei and Rolf Gruetter in Journal of Cerebral Blood Flow & Metabolism

Proton MRS (1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.

Balanced steady-state free precession (bSSFP) can be used as an alternative to gradient-echo (GE) EPI for BOLD functional MRI when image distortions and signal drop-outs are severe such as at ultra-high field. However, 3D-bSSFP acquisitions have distinct drawbacks on either human or animal MR systems. On clinical scanners, 3D imaging is suboptimal for localized fMRI applications, and also results in distortions, blurring, and increased sensitivity to motion or physiological noise. On pre-clinical systems, 3D acquisitions have low temporal resolution due to limited acceleration options, while single slice offers insufficient coverage. The aim of the present study was to implement a multi-slice bSSFP acquisition with Cartesian read-out to obtain non-distorted BOLD fMRI activation maps in the human and rat brain at ultra-high field. We show that the bSSFP signal characteristics are preserved in a new pseudo-steady-state. In the human brain at 7 Tesla, we demonstrate that both task- and resting-state fMRI can be performed with 2D-bSSFP, with a temporal SNR that matches that of 3D-bSSFP, resulting in - at least - equal performance. In the rat brain at 14 Tesla, we show that the multi-slice bSSFP protocol has similar sensitivity to gradient-echo EPI for task fMRI, while benefitting from much reduced distortions and drop-outs. The advantages of passband bSSFP at 14 Tesla in comparison with GE-EPI are expected to be even more marked for mouse fMRI.

Item does not contain fulltext A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. © RSNA, 2014 Online supplemental material is available for this article.

© 2015 John Wiley Sons Ltd. Blood oxygenation level dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies the BOLD response is typically limited to a few minutes in animal models due to fatigue anesthesia effects and physiological instability. In the present study the rat forepaw was electrically stimulated for 2 h which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm including an inter stimulus interval (ISI) of 10 s that is 25 of the total time was applied at constant or variable frequency over 2 h. The steady state level of the BOLD response was reached after 15 20 min of stimulation and was maintained until the end of the stimulation. On average no substantial loss in activated volume was observed at the end of the stimulation but less variability in the fraction of remaining activated volume and higher steady state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust prolonged and localized BOLD activation.

Hyperpolarization by dissolution dynamic nuclear polarization (DNP) is a versatile technique to dramatically enhance the nuclear magnetic resonance (NMR) signal intensity of insensitive long-T1 nuclear spins such as (6)Li. The (6)Li longitudinal relaxation of lithium ions in aqueous solutions strongly depends on the concentration of paramagnetic species, even if they are present in minute amounts. We herein demonstrate that blood oxygenation can be readily detected by taking advantage of the (6)Li signal enhancement provided by dissolution DNP, together with the more than 10% decrease in (6)Li longitudinal relaxation as a consequence of the presence of paramagnetic deoxyhemoglobin.

PURPOSE: Multinuclear magnetic resonance spectroscopy and imaging require a radiofrequency probe capable of transmitting and receiving at the proton and non-proton frequencies. To minimize coupling between probe elements tuned to different frequencies, LC (inductor-capacitor) traps blocking current at the 1 H frequency can be inserted in non-proton elements. This work compares LC traps with LCC traps, a modified design incorporating an additional capacitor, enabling control of the trap reactance at the low frequency while maintaining 1 H blocking. METHODS: Losses introduced by both types of trap were analysed using circuit models. Radiofrequency coils incorporating a series of LC and LCC traps were then built and evaluated at the bench. LCC trap performance was then confirmed using 1 H and 13 C measurements in a 7T human scanner. RESULTS: LC and LCC traps both effectively block interaction between non-proton and proton coils at the proton frequency. LCC traps were found to introduce a sensitivity reduction of 5+/-2%, which was less than half of that caused by LC traps. CONCLUSION: Sensitivity of non-proton coils is critical. The improved trap design, incorporating one extra capacitor, significantly reduces losses introduced by the trap in the non-proton coil.

Purpose As the magnetic susceptibility induced frequency shift increases linearly with magnetic field strength, the present work evaluates manganese as a phase imaging contrast agent and investigates the dose dependence of brain enhancement in comparison to T1-weighted imaging after intravenous administration of MnCl2. Methods Experiments were carried out on 12 Sprague-Dawley rats. MnCl2 was infused intravenously with the following doses: 25, 75, 125 mg/kg (n=4). Phase, T1-weighted images and T1 maps were acquired before and 24h post MnCl2 administration at 14.1 Tesla. Results Manganese enhancement was manifested in phase imaging by an increase in frequency shift differences between regions rich in calcium gated channels and other tissues, together with local increase in signal to noise ratio (from the T1 reduction). Such contrast improvement allowed a better visualization of brain cytoarchitecture. The measured T1 decrease observed across different manganese doses and in different brain regions were consistent with the increase in the contrast to noise ratio (CNR) measured by both T1-weighted and phase imaging, with the strongest variations being observed in the dentate gyrus and olfactory bulb. Conclusion Overall from its high sensitivity to manganese combined with excellent CNR, phase imaging is a promising alternative imaging protocol to assess manganese enhanced MRI at ultra high field.

After the landmark studies reporting changes in the cerebral metabolic rate of glucose (CMR(Glc) ) in excess of those in oxygen (CMR(O2) ) during physiological stimulation, several studies have examined the fate of the extra carbon taken up by the brain, reporting a wide range of changes in brain lactate from 20% to 250%. The present study reports functional magnetic resonance spectroscopy measurements at 7 Tesla using the enhanced sensitivity to study a small cohort (n = 6). Small increases in lactate (19% ± 4%, P < 0.05) and glutamate (4% ± 1%, P < 0.001) were seen within the first 2 min of activation. With the exception of glucose (12% ± 5%, P < 0.001), no other metabolite concentration changes beyond experimental error were significantly observed. Therefore, the present study confirms that lactate and glutamate changes during physiological stimulation are small (i.e. below 20%) and shows that the increased sensitivity allows reproduction of previous results with fewer subjects. In addition, the initial rate of glutamate and lactate concentration increases implies an increase in CMR(O2) that is slightly below that of CMR(Glc) during the first 1-2 min of activation. © 2013 Wiley Periodicals, Inc.

The recent developments in high magnetic field 13C magnetic resonance spectroscopy with improved localization and shimming techniques have led to important gains in sensitivity and spectral resolution of 13C in vivo spectra in the rodent brain, enabling the separation of several 13C isotopomers of glutamate and glutamine. In this context, the assumptions used in spectral quantification might have a significant impact on the determination of the 13C concentrations and the related metabolic fluxes. In this study, the time domain spectral quantification algorithm AMARES (advanced method for accurate, robust and efficient spectral fitting) was applied to 13 C magnetic resonance spectroscopy spectra acquired in the rat brain at 9.4 T, following infusion of [1,6-(13)C2 ] glucose. Using both Monte Carlo simulations and in vivo data, the goal of this work was: (1) to validate the quantification of in vivo 13C isotopomers using AMARES; (2) to assess the impact of the prior knowledge on the quantification of in vivo 13C isotopomers using AMARES; (3) to compare AMARES and LCModel (linear combination of model spectra) for the quantification of in vivo 13C spectra. AMARES led to accurate and reliable 13C spectral quantification similar to those obtained using LCModel, when the frequency shifts, J-coupling constants and phase patterns of the different 13C isotopomers were included as prior knowledge in the analysis.

The broad resonances underlying the entire (1) H NMR spectrum of the brain, ascribed to macromolecules, can influence metabolite quantification. At the intermediate field strength of 3 T, distinct approaches for the determination of the macromolecule signal, previously used at either 1.5 or 7 T and higher, may become equivalent. The aim of this study was to evaluate, at 3 T for healthy subjects using LCModel, the impact on the metabolite quantification of two different macromolecule approaches: (i) experimentally measured macromolecules; and (ii) mathematically estimated macromolecules. Although small, but significant, differences in metabolite quantification (up to 23% for glutamate) were noted for some metabolites, 10 metabolites were quantified reproducibly with both approaches with a Cramer-Rao lower bound below 20%, and the neurochemical profiles were therefore similar. We conclude that the mathematical approximation can provide sufficiently accurate and reproducible estimation of the macromolecule contribution to the (1) H spectrum at 3 T. Copyright © 2013 John Wiley & Sons, Ltd.

Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state conformational model of glucose transport than with any of the other models tested. Furthermore, we confirmed the utility of the present method to determine glucose transport and consumption by analysing the modulation of both glucose transport and consumption by anaesthesia conditions that modify cerebral activity. In particular, deep thiopental anaesthesia caused a significant reduction of both T(max) and cerebral metabolic rate for glucose consumption. In conclusion, dynamic measurement of brain glucose in vivo in function of plasma glucose allows robust determination of both glucose uptake and consumption kinetics.

Proton T(1) relaxation times of metabolites in the human brain have not previously been published at 7 T. In this study, T(1) values of CH(3) and CH(2) group of N-acetylaspartate and total creatine as well as nine other brain metabolites were measured in occipital white matter and gray matter at 7 T using an inversion-recovery technique combined with a newly implemented semi-adiabatic spin-echo full-intensity acquired localized spectroscopy sequence (echo time = 12 ms). The mean T(1) values of metabolites in occipital white matter and gray matter ranged from 0.9 to 2.2 s. Among them, the T(1) of glutathione, scyllo-inositol, taurine, phosphorylethanolamine, and N-acetylaspartylglutamate were determined for the first time in the human brain. Significant differences in T(1) between white matter and gray matter were found for water (-28%), total choline (-14%), N-acetylaspartylglutamate (-29%), N-acetylaspartate (+4%), and glutamate (+8%). An increasing trend in T(1) was observed when compared with previously reported values of N-acetylaspartate (CH(3) ), total creatine (CH(3) ), and total choline at 3 T. However, for N-acetylaspartate (CH(3) ), total creatine, and total choline, no substantial differences compared to previously reported values at 9.4 T were discernible. The T(1) values reported here will be useful for the quantification of metabolites and signal-to-noise optimization in human brain at 7 T. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

P>The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.

In this study, hypothalamic activation was performed by dehydration-induced anorexia (DIA) and overnight food suppression (OFS) in female rats. The assessment of the hypothalamic response to these challenges by manganese-enhanced MRI showed increased neuronal activity in the paraventricular nuclei (PVN) and lateral hypothalamus (LH), both known to be areas involved in the regulation of food intake. The effects of DIA and OFS were compared by generating T-score maps. Increased neuronal activation was detected in the PVN and LH of DIA rats relative to OFS rats. In addition, the neurochemical profile of the PVN and LH were measured by (1) H MRS at 14.1T. Significant increases in metabolite levels were measured in DIA and OFS relative to control rats. Statistically significant increases in γ-aminobutyric acid were found in DIA (p=0.0007) and OFS (p

The hypothalamus plays an essential role in the central nervous system of mammals by among others regulating glucose homeostasis, food intake, temperature, and to some extent blood pressure. Assessments of hypothalamic metabolism using, e.g. (1)H MRS in mouse models can provide important insights into its function. To date, direct in vivo (1)H MRS measurements of hypothalamus have not been reported. Here, we report that in vivo single voxel measurements of mouse hypothalamus are feasible using (1)H MRS at 14.1T. Localized (1)H MR spectra from hypothalamus were obtained unilaterally (2-2.2 microL, VOI) and bilaterally (4-4.4 microL) with a quality comparable to that of hippocampus (3-3.5 microL). Using LCModel, a neurochemical profile consisting of 21 metabolites was quantified for both hypothalamus and hippocampus with most of the Cramér-Rao lower bounds within 20%. Relative to the hippocampus, the hypothalamus was characterized by high gamma-aminobutryric acid and myo-inositol, and low taurine concentrations. When studying transgenic mice with no glucose transporter isoform 8 expressed, small metabolic changes were observed, yet glucose homeostasis was well maintained. We conclude that a specific neurochemical profile of mouse hypothalamus can be measured by (1)H MRS which will allow identifying and following metabolic alterations longitudinally in the hypothalamus of genetic modified models.

1H MRS was employed at 14.1T to non-invasively quantify the lipid content of small samples (8-15 µl). In the mouse liver, good spectral stability was achieved by running individual scans within one breathing cycle. Ultra short TE STEAM with water suppression was used to estimate the unsaturation profile of the fatty acyl chains. This method was in good agreement with in vitro measurements in phantoms. High field is advantageous to accurately characterize the lipid profile of small samples such as the volumes selected in the liver of mice, with no need to increase the acquisition time for sensitivity gain.

The hepatic lipid content and composition were assessed in healthy mice throughout adulthood. It was found that aging and obesity contributed to increase the amount of lipids in the liver while decreasing the poly-unsaturation degree. The combination of in vivo 1H MRS assessments with in vitromeasurements on tissues extracts illustrated the important contribution of membrane lipids to the total poly-unsaturation degree of the fatty acyl chains. Changes of the unsaturation profile of cytosolic lipids can be monitored by in vivo 1H MRS, which is of interest for the study of genetic and diet-induced mice models of metabolic diseases.

Cerebral glucose homeostasis is maintained by the equilibrium between glucose transport across the blood-brain-barrier (BBB), which occurs through facilitative carriers, and glucose consumption mainly initiated by hexokinase phosphorylation. Glucose concentrations can be quantified non invasively by nuclear magnetic resonance (NMR) spectroscopy and such measurements, through appropriate mathematical modelling, allow to determine the kinetics of glucose transport and metabolism. This chapter summarizes the insights gained into brain glucose transport from the measurement of the brain glucose concentration, particularly reviewing state of the art NMR methods for non invasive determination of glucose homeostasis and discussing the employment of mathematical models of glucose transport.

The LCModel method was adapted to analyze localized in vivo (13)C NMR spectra obtained from the rat brain in vivo at 9.4 T. Prior knowledge of chemical-shifts, J-coupling constants and J-evolution was included in the analysis. Up to 50 different isotopomer signals corresponding to 10 metabolites were quantified simultaneously in 400 microl volumes in the rat brain in vivo during infusion of [1,6-(13)C(2)]glucose. The analysis remained accurate even at low signal-to-noise ratio of the order of 3:1. The relative distribution of isotopomers in glutamate, glutamine and aspartate determined in vivo in 22 min was in excellent agreement with that measured in brain extracts. Quantitation of time series of (13)C spectra yielded time courses of total (13)C label incorporation into up to 16 carbon positions, as well as time courses of individual isotopomer signals, with a temporal resolution as low as 5 min (dynamic isotopomer analysis). The possibility of measuring in vivo a wealth of information that was hitherto accessible only in extracts is likely to expand the scope of metabolic studies in the intact brain.

d-amino acid oxidase (DAO) is a peroxisomal enzyme that catalyzes the oxidative deamination of several neutral and basic d-amino acids to their corresponding alpha-keto acids. In most mammalian species studied, high DAO activity is found in the kidney, liver, brain and polymorphonuclear leukocytes, and its main function is to maintain low circulating d-amino acid levels. DAO expression and activity have been associated with acute and chronic kidney diseases and with several pathologies related to N-methyl-d-aspartate (NMDA) receptor hypo/hyper-function; however, its precise role is not completely understood. In the present study we show that DAO activity can be detected in vivo in the rat kidney using hyperpolarized d-[1-C-13]alanine. Following a bolus of hyperpolarized d-alanine, accumulation of pyruvate, lactate and bicarbonate was observed only when DAO activity was not inhibited. The measured lactate-to-d-alanine ratio was comparable to the values measured when the l-enantiomer was injected. Metabolites downstream of DAO were not observed when scanning the liver and brain. The conversion of hyperpolarized d-[1-C-13]alanine to lactate and pyruvate was detected in blood ex vivo, and lactate and bicarbonate were detected on scanning the blood pool in the heart in vivo; however, the bicarbonate-to-d-alanine ratio was significantly lower compared with the kidney. These results demonstrate that the specific metabolism of the two enantiomers of hyperpolarized [1-C-13]alanine in the kidney and in the blood can be distinguished, underscoring the potential of d-[1-C-13]alanine as a probe of d-amino acid metabolism.

The real-time metabolic transformation of lactate in the mouse head was monitored following the injection of hyperpolarized 1-13C lactate at physiological doses. The results were compared with metabolic studies performed with hyperpolarized 1-13C pyruvate at similar blood concentration. From the observation that the lactate to alanine ratio was nearly identical following both the pyruvate and the lactate injections, we concluded that the substrate and its metabolites can be detected in real time at physiological concentrations after the injection of lactate.

Trapped coil designs allow the operation of lower-frequency coils in the presence of a proton coil. Adding a second capacitor to a trap in the non-proton RF coil allows control over the trap reactance at the low and high frequency (here 13C and 1H) and the frequency of the trap mode. We demonstrate the interdependence of the parameters controlled and show analytical and numerical solutions to fulfill the design constraints. Our experiments show that, using the simulations, it possible to construct an effective second order trap for 13C at 7T.

Acetate has been proposed as an astrocyte-specific energy substrate for metabolic studies in the brain. The determination of the relative contribution of the intracellular and extracellular compartments to the acetate signal using diffusion-weighted magnetic resonance spectroscopy can provide an insight into the cellular environment and distribution volume of acetate in the brain. In the present study, localized (1) H nuclear magnetic resonance (NMR) spectroscopy employing a diffusion-weighted stimulated echo acquisition mode (STEAM) sequence at an ultra-high magnetic field (14.1 T) was used to investigate the diffusivity characteristics of acetate and N-acetylaspartate (NAA) in the rat brain in vivo during prolonged acetate infusion. The persistence of the acetate resonance in (1) H spectra acquired at very large diffusion weighting indicated restricted diffusion of acetate and was attributed to intracellular spaces. However, the significantly greater diffusion of acetate relative to NAA suggests that a substantial fraction of acetate is located in the extracellular space of the brain. Assuming an even distribution for acetate in intracellular and extracellular spaces, the diffusion properties of acetate yielded a smaller volume of distribution for acetate relative to water and glucose in the rat brain.

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.

The concept of second order proton traps (consisting of an inductor and two capacitors) in coils for non-proton NMR allows control over the resonance frequency, the blocking frequency and the trap mode frequency. Effective proton traps with relatively high LTr, and thus very effective blocking, can be constructed, which impose only small degradation of the non-1H coil sensitivity.

Knowledge of proton T-2 relaxation time of metabolites is essential for proper quantitation of metabolite concentrations in localized proton spectroscopy, especially at moderate to long TEs. Although the T-2 relaxation time of singlets, such as that of creatine and N-acetylaspartate, has been characterized in several studies, similar information is lacking from coupled spin resonances of cerebral metabolites. In this study, the T-2 relaxation time of coupled spin resonances and singlet resonances of cerebral metabolites was measured in rat brain in vivo at 9.4T. Spectra were acquired at 11 TEs using the SPin ECho, full Intensity Acquired Localized (SPECIAL) spectroscopy method. Data analysis was performed in the frequency domain with the LCModel software using simulated TE-specific basis sets. The T-2 relaxation times in compounds showing singlet resonances were 113 +/- 3 ms (total creatine), 178 +/- 29 ms (total choline) and 202 +/- 12 ms (N-acetylaspartate). The T-2 values of J-coupled metabolites ranged from 89 +/- 8 ms (glutamate) to 148 +/- 14 ms (myo-inositol). Copyright (C) 2007 John Wiley & Sons, Ltd.

The combination of dynamic (13)C MRS data under infusion of (13)C-labeled substrates and compartmental models of cerebral metabolism enabled in vivo measurement of metabolic fluxes with a quantitative and distinct determination of cellular-specific activities. The non-invasive nature and the chemical specificity of the (13)C dynamic data obtained in those tracer experiments makes it an attractive approach offering unique insights into cerebral metabolism. Genetically engineered mice present a wealth of disease models particularly interesting for the neuroscience community. Nevertheless, in vivo(13)C NMR studies of the mouse brain are only recently appearing in the field due to the numerous challenges linked to the small mouse brain volume and the difficulty to follow the mouse physiological parameters within the NMR system during the infusion experiment. This review will present the progresses in the quest for a higher in vivo(13)C signal-to-noise-ratio up to the present state of the art techniques, which made it feasible to assess glucose metabolism in different regions of the mouse brain. We describe how experimental results were integrated into suitable compartmental models and how a deep understanding of cerebral metabolism depends on the reliable detection of (13)C in the different molecules and carbon positions.

The aim of this study is to perform a thorough comparison of quantitative susceptibility mapping (QSM) techniques and their dependence on the assumptions made. The compared methodologies were: two iterative single orientation methodologies minimizing the l2, l1TV norm of the prior knowledge of the edges of the object, one over-determined multiple orientation method (COSMOS) and anewly proposed modulated closed-form solution (MCF). The performance of these methods was compared using a numerical phantom and in-vivo high resolution (0.65 mm isotropic) brain data acquired at 7 T using a new coil combination method. For all QSM methods, the relevant regularization and prior-knowledge parameters were systematically changed in order to evaluate the optimal reconstruction in the presence and absence of a ground truth. Additionally, the QSM contrast was compared to conventional gradient recalled echo (GRE) magnitude and R2* maps obtained from the same dataset. The QSM reconstruction results of the single orientation methods show comparable performance. The MCF method has the highest correlation (corrMCF = 0.95, r2MCF = 0.97) with the state of the art method (COSMOS) with additional advantage of extreme fast computation time. The l-curve method gave the visually most satisfactory balance between reduction of streaking artifacts and over-regularization with the latter being overemphasized when the using the COSMOS susceptibility maps as ground-truth. R2* and susceptibility maps, when calculated from the same datasets, although based on distinct features of the data, have a comparable ability to distinguish deep gray matter structures.

Despite obvious improvements in spectral resolution at high magnetic field, the detection of C-13 labeling by H-1-[C-13] NMR spectroscopy remains hampered by spectral overlap, such as in the spectral region of H-1 resonances bound to C3 of glutamate (Glu) and glutamine (Gin), and C6 of N-acetylaspartate (NAA). The aim of this study was to develop, implement, and apply a novel H-1-[C-13] NMR spectroscopic editing scheme, dubbed "selective Resonance suppression by Adiabatic Carbon Editing and Decoupling single-voxel STimulated Echo Acquisition Mode" (RACED-STEAM). The sequence is based on the application of two asymmetric narrow-transition-band adiabatic RF inversion pulses at the resonance frequency of the C-13 coupled to the protons that need to be suppressed during the mixing time (TM) period, alternating the inversion band downfield and upfield from the C-13 resonance on odd and even scans, respectively, thus suppressing the detection of H-1 resonances bound to C-13 within the transition band of the inversion pulse. The results demonstrate the efficient suppression of H-1 resonances bound to C3 of Glu and Gin, and C4 of Glu, which allows the H-1 resonances bound to C6 of NAA and C4 of Gin to be revealed. The measured time course of the resolved labeling into NAA C6 with the new scheme was consistent with the slow turnover of NAA. Magn Reson Med 61:260-266, 2009. (c) 2009 Wiley-Liss, Inc.

PURPOSE: At high magnetic field strengths (B0 >/= 3 T), the shorter radiofrequency wavelength produces an inhomogeneous distribution of the transmit magnetic field. This can lead to variable contrast across the brain which is particularly pronounced in T2 -weighted imaging that requires multiple radiofrequency pulses. To obtain T2 -weighted images with uniform contrast throughout the whole brain at 7 T, short (2-3 ms) 3D tailored radiofrequency pulses (kT -points) were integrated into a 3D variable flip angle turbo spin echo sequence. METHODS: The excitation and refocusing "hard" pulses of a variable flip angle turbo spin echo sequence were replaced with kT -point pulses. Spatially resolved extended phase graph simulations and in vivo acquisitions at 7 T, utilizing both single channel and parallel-transmit systems, were used to test different kT -point configurations. RESULTS: Simulations indicated that an extended optimized k-space trajectory ensured a more homogeneous signal throughout images. In vivo experiments showed that high quality T2 -weighted brain images with uniform signal and contrast were obtained at 7 T by using the proposed methodology. CONCLUSION: This work demonstrates that T2 -weighted images devoid of artifacts resulting from B1 + inhomogeneity can be obtained at high field through the optimization of extended kT -point pulses.

The recent developments in high magnetic field (13) C magnetic resonance spectroscopy with improved localization and shimming techniques have led to important gains in sensitivity and spectral resolution of (13) C in vivo spectra in the rodent brain, enabling the separation of several (13) C isotopomers of glutamate and glutamine. In this context, the assumptions used in spectral quantification might have a significant impact on the determination of the (13) C concentrations and the related metabolic fluxes. In this study, the time domain spectral quantification algorithm AMARES (advanced method for accurate, robust and efficient spectral fitting) was applied to (13) C magnetic resonance spectroscopy spectra acquired in the rat brain at 9.4 T, following infusion of [1,6-(13) C(2) ] glucose. Using both Monte Carlo simulations and in vivo data, the goal of this work was: (1) to validate the quantification of in vivo (13) C isotopomers using AMARES; (2) to assess the impact of the prior knowledge on the quantification of in vivo (13) C isotopomers using AMARES; (3) to compare AMARES and LCModel (linear combination of model spectra) for the quantification of in vivo (13) C spectra. AMARES led to accurate and reliable (13) C spectral quantification similar to those obtained using LCModel, when the frequency shifts, J-coupling constants and phase patterns of the different (13) C isotopomers were included as prior knowledge in the analysis. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.