Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE 1H MRS at 7 T

The two‐fold benefit of ¹H magnetic resonance spectroscopy (MRS) at high B₀ fields – enhanced sensitivity and increased spectral dispersion – has been used previously to study dynamic changes in metabolite concentrations in the human brain in response to visual stimulation. In these studies, a strong visual on/off stimulus was combined with MRS data acquisition in a voxel location in the occipital cortex determined by an initial functional magnetic resonance imaging experiment. However, 1) to exclude the possibility of systemic effects (heartbeat, blood flow, etc.), which tend to be different for on/off conditions, a modified stimulation condition not affecting the target voxel needs to be employed, and 2) to assess important neurotransmitters of low concentration, in particular γ‐aminobutyric acid (GABA), it may be advantageous to analyze steady‐state, rather than dynamic, conditions. Thus, the aim of this study was to use short‐TE ¹H MRS methodology at 7 T to detect differences in steady‐state metabolite levels in response to a varying stimulation paradigm in the human visual cortex. The two different stimulation conditions were termed voxel and control activation. Localized MR spectra were acquired using the SPECIAL (spin‐echo full‐intensity acquired localized) sequence. Data were analyzed using LCModel. Fifteen individual metabolites were reliably quantified. On comparison of steady‐state concentrations for voxel versus control activation, a decrease in GABA of 0.05 mmol/L (5%) and an increase in lactate of 0.04 mmol/L (7%) were found to be the only significant effects. The observed reduction in GABA can be interpreted as reduced neuronal inhibition during voxel activation, whereas the increase in lactate hints at an intensification of anaerobic glycolysis. Differences from previous studies, notably the absence of any changes in glutamate, are attributed to the modified experimental conditions. This study demonstrates that the use of advanced ¹H MRS methodology at 7 T allows the detection of subtle changes in metabolite concentrations involved in neuronal activation and inhibition.     

Electrocardiogram‐triggered,higher order,projection‐based B0 shimming allows for fast and reproducible shim convergence in spinal cord 1H MRS

¹H MRS allows insight into the chemical composition of the central nervous system. However, as a result of technical challenges, it has rarely been applied to the spinal cord. In particular, the strong susceptibility changes around the spinal cord and the pulsatile flow of the cerebrospinal fluid lead to distinct B₀ field distortions which often considerably degrade the spectral quality. Hence, B₀ shimming is one of the main challenges in ¹H MRS of the spinal cord. Electrocardiogram (ECG)‐triggered, higher order, projection‐based B₀ shimming was introduced and compared with both conventional projection‐based B₀ shimming and B₀ shimming based on ECG‐triggered, three‐dimensional B₀ field mapping. The linewidth of the unsuppressed water peak was used to evaluate the reproducibility and the potential improvement to B₀ homogeneity. The use of ECG‐triggered projection‐based B₀ shimming in combination with ECG triggering during preparation phases and triggering during acquisition of the spectra is the most robust method and thus helps to improve the spectral quality for MRS of the spinal cord. Copyright © 2012 John Wiley & Sons, Ltd.     

Navigator based respiratory gating during acquisition and preparation phases for proton liver spectroscopy at 3 T

Proton magnetic resonance spectroscopy (¹H MRS) enables the non‐invasive investigation of the human liver; however, because of technical difficulties it is not regularly used for diagnosis of liver diseases in clinical routine. Breathing motion is one of the major challenges, as it decreases spectral quality and leads to misplacement of the spectroscopic voxel. To overcome this problem, real‐time navigator gating for spectral acquisition and preparation steps (B₀ shimming, water frequency determination, receiver gain optimization, and water suppression) combined with short T_E, optimized first order projection based B₀ shimming, water suppression, and inner‐volume saturated point resolved spectroscopy (PRESS) at 3 T is suggested. Simultaneous lipid and trimethylamine quantification is demonstrated by means of phantom, volunteer, and representative patient measurements. Precise localization of the voxel despite respiratory motion, increased spectral quality (higher signal‐to‐noise ratio and reduced linewidth) compared with measurements without respiratory gating, and the possibility of acquiring data without additional subject instructions regarding breathing enable robust and accurate liver ¹H MRS measurements with this novel acquisition protocol. Copyright © 2014 John Wiley & Sons, Ltd.     

Neurochemical profile of the mouse hypothalamus using in vivo 1H MRS at 14.1T

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. ¹H MRS in mouse models can provide important insights into its function. To date, direct in vivo ¹H MRS measurements of hypothalamus have not been reported. Here, we report that in vivo single voxel measurements of mouse hypothalamus are feasible using ¹H MRS at 14.1T. Localized ¹H MR spectra from hypothalamus were obtained unilaterally (2–2.2 µL, VOI) and bilaterally (4–4.4 µL) with a quality comparable to that of hippocampus (3–3.5 µL). 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 γ‐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 ¹H MRS which will allow identifying and following metabolic alterations longitudinally in the hypothalamus of genetic modified models. Copyright © 2010 John Wiley & Sons, Ltd.     

Interleaved 31P MRS imaging of human frontal and occipital lobes using dual RF coils in combination with single‐channel transmitter–receiver and dynamic B0 shimming

In vivo ³¹P magnetic resonance spectroscopy (MRS) provides a unique tool for the non‐invasive study of brain energy metabolism and mitochondrial function. The assessment of bioenergetic impairment in different brain regions is essential to understand the pathophysiology and progression of human brain diseases. This article presents a simple and effective approach which allows the interleaved measurement of ³¹P spectra and imaging from two distinct human brain regions of interest with dynamic B₀ shimming capability. A transistor–transistor logic controller was employed to actively switch the single‐channel X‐nuclear radiofrequency (RF) transmitter–receiver between two ³¹P RF surface coils, enabling the interleaved acquisition of two ³¹P free induction decays (FIDs) from human occipital and frontal lobes within the same repetition time. Linear gradients were incorporated into the RF pulse sequence to perform the first‐order dynamic shimming to further improve spectral resolution. The overall results demonstrate that the approach provides a cost‐effective and time‐efficient solution for reliable ³¹P MRS measurement of cerebral phosphate metabolites and adenosine triphosphate (ATP) metabolic fluxes from two human brain regions with high detection sensitivity and spectral quality at 7 T. The same design concept can be extended to acquire multiple spectra from more than two brain regions or can be employed for other magnetic resonance applications beyond the ³¹P spin.     

Localized 1H NMR spectroscopy in different regions of human brain in vivo at 7 T: T2 relaxation times and concentrations of cerebral metabolites

At the high field strength of 7 T, in vivo spectra of the human brain with exceptional spectral quality sufficient to quantify 16 metabolites have been obtained previously only in the occipital lobe. However, neurochemical abnormalities associated with many brain disorders are expected to occur in brain structures other than the occipital lobe. The purpose of the present study was to obtain high‐quality spectra from various brain regions at 7 T and to quantify the concentrations of different metabolites. To obtain concentrations of metabolites within four different regions of the brain, such as the occipital lobe, motor cortex, basal ganglia and cerebellum, the T₂ relaxation times of the singlets and J‐coupled metabolites in these regions were measured for the first time at 7 T. Our results demonstrate that high‐quality, quantifiable spectra can be obtained in regions other than the occipital lobe at 7 T utilizing a 16‐channel transceiver coil and B₁⁺ shimming. Copyright © 2011 John Wiley & Sons, Ltd.     

Two‐voxel spectroscopy with dynamic B0 shimming and flip angle adjustment at 7 T in the human motor cortex

The aim of this study was to acquire high‐quality in vivo ¹H spectra concurrently from two voxels at ultra‐high field (7 T) without specialized hardware. To this end, an acquisition scheme was developed in which first‐order shims and flip angles are dynamically updated to acquire spectra from both of the brain's motor cortices in an alternating fashion. To validate this acquisition scheme, separate, static, single‐voxel acquisitions were also performed for comparison. Six subjects were examined using semi‐LASER spectroscopy at 7 T. Barium titanate pads were used to increase the extent of the effective transmit field (B₁⁺). Spectra were obtained from the hand area of both motor cortices for both acquisition schemes. LCModel was used to determine neurochemical profiles in order to examine variations between acquisition schemes and volumes of interest. The dynamic two‐voxel acquisition protocol produced water linewidths (full width at half‐maximum between 11.6 and 12.8 Hz) and signal‐to‐noise ratios similar to those from static single‐voxel measurements. The concentrations of 13 individual and 3 combined metabolites with Cramér–Rao lower bounds below 30% were reliably detected for both acquisition schemes, and agreed well with previous postmortem assay and spectroscopy studies. The results show that high spectral quality from two voxels can be acquired concurrently without specialized hardware. This practical technique can be applied to many neuroscience applications. Copyright © 2015 John Wiley & Sons, Ltd.     

MASE‐sLASER,a short‐TE,matched chemical shift displacement error sequence for single‐voxel spectroscopy at ultrahigh field

B₁ inhomogeneity and chemical shift displacement error (CSDE) increase with the main magnetic field strength and are therefore deleterious for magnetic resonance spectroscopy (MRS) at ultrahigh field. A solution is to use adiabatic pulses which operate over a broad range of B₁ and thus are insensitive to B₁ inhomogeneity. Moreover, adiabatic pulses usually have a relatively higher bandwidth, which makes CSDE low to negligible. The use of exclusively adiabatic pulses for single‐voxel spectroscopy (SVS) typically brings the disadvantage of a long echo time (TE), but the advantage of a low and matched CSDE. Herein, we took advantage of short‐duration, low‐power, matched‐phase adiabatic spin echo (MASE) pulses to implement a matched CSDE semi‐localized by adiabatic selective refocusing (sLASER) sequence capable of attaining short TEs, while CSDE is matched and still comparatively low. We also demonstrate here the feasibility of the direct measurement of the γ‐aminobutyric acid (GABA) resonance at 2.28 ppm well separated from the neighboring glutamate resonance at 7 T using the implemented MASE‐sLASER sequence at TEs of 68 and 136 ms. The shorter duration of MASE pulses also made it possible to implement a Mescher–Garwood‐semi‐localized by adiabatic selective refocusing (MEGA‐sLASER) (with MASE) sequence with TE = 68 ms for editing GABA at 7 T, the results for which are also shown.     

Slice‐selective FID acquisition,localized by outer volume suppression (FIDLOVS) for 1H‐MRSI of the human brain at 7 T with minimal signal loss

In comparison to 1.5 and 3 T, MR spectroscopic imaging at 7 T benefits from signal‐to‐noise ratio (SNR) gain and increased spectral resolution and should enable mapping of a large number of metabolites at high spatial resolutions. However, to take full advantage of the ultra‐high field strength, severe technical challenges, e.g. related to very short T₂ relaxation times and strict limitations on the maximum achievable B₁ field strength, have to be resolved. The latter results in a considerable decrease in bandwidth for conventional amplitude modulated radio frequency pulses (RF‐pulses) and thus to an undesirably large chemical‐shift displacement artefact. Frequency‐modulated RF‐pulses can overcome this problem; but to achieve a sufficient bandwidth, long pulse durations are required that lead to undesirably long echo‐times in the presence of short T₂ relaxation times. In this work, a new magnetic resonance spectroscopic imaging (MRSI) localization scheme (free induction decay acquisition localized by outer volume suppression, FIDLOVS) is introduced that enables MRSI data acquisition with minimal SNR loss due to T₂ relaxation and thus for the first time mapping of an extended neurochemical profile in the human brain at 7 T. To overcome the contradictory problems of short T₂ relaxation times and long pulse durations, the free induction decay (FID) is directly acquired after slice‐selective excitation. Localization in the second and third dimension and skull lipid suppression are based on a T₁‐ and B₁‐insensitive outer volume suppression (OVS) sequence. Broadband frequency‐modulated excitation and saturation pulses enable a minimization of the chemical‐shift displacement artefact in the presence of strict limits on the maximum B₁ field strength. The variable power RF pulses with optimized relaxation delays (VAPOR) water suppression scheme, which is interleaved with OVS pulses, eliminates modulation side bands and strong baseline distortions. Third order shimming is based on the accelerated projection‐based automatic shimming routine (FASTERMAP) algorithm. The striking SNR and spectral resolution enable unambiguous quantification and mapping of 12 metabolites including glutamate (Glu), glutamine (Gln), N‐acetyl‐aspartatyl‐glutamate (NAAG), γ‐aminobutyric acid (GABA) and glutathione (GSH). The high SNR is also the basis for highly spatially resolved metabolite mapping. Copyright © 2009 John Wiley & Sons, Ltd.     

Covariance J‐resolved spectroscopy: Theory and application in vivo

Magnetic resonance spectroscopy (MRS) is a powerful tool capable of investigating the metabolic status of several tissues in vivo. In particular, single‐voxel‐based ¹H spectroscopy provides invaluable biochemical information from a volume of interest (VOI) and has therefore been used in a variety of studies. Unfortunately, typical one‐dimensional MRS data suffer from severe signal overlap and thus important metabolites are difficult to distinguish. One method that is used to disentangle overlapping resonances is the two‐dimensional J‐resolved spectroscopy (JPRESS) experiment. Due to the long acquisition duration of the JPRESS experiment, a limited number of points are acquired in the indirect dimension, leading to poor spectral resolution along this dimension. Poor spectral resolution is problematic because proper peak assignment may be hindered, which is why the zero‐filling method is often used to improve resolution as a post‐processing step. However, zero‐filling leads to spectral artifacts, which may affect visualization and quantitation of spectra. A novel method utilizing a covariance transformation, called covariance J‐resolved spectroscopy (CovJ), was developed in order to improve spectral resolution along the indirect dimension (F₁). Comparison of simulated data demonstrates that peak structures remain qualitatively similar between JPRESS and the novel method along the diagonal region (F₁ = 0 Hz), whereas differences arise in the cross‐peak (F₁≠0 Hz) regions. In addition, quantitative results of in vivo JPRESS data acquired on a 3T scanner show significant correlations (r²>0.86, p<0.001) when comparing the metabolite concentrations between the two methods. Finally, a quantitation algorithm, ‘COVariance Spectral Evaluation of ¹H Acquisitions using Representative prior knowledge’ (Cov‐SEHAR), was developed in order to quantify γ‐aminobutyric acid and glutamate from the CovJ spectra. These preliminary findings indicate that the CovJ method may be used to improve spectral resolution without hindering metabolite quantitation for J‐resolved spectra.     

Measurement of regional variation of GABA in the human brain by optimized point‐resolved spectroscopy at 7 T in vivo

The ¹H resonances of γ‐aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short‐TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point‐resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE₂) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T₁‐weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N‐acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J‐coupled spin metabolites in human brain at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.     

High‐resolution spatial mapping of changes in the neurochemical profile after focal ischemia in mice

After ischemic stroke, the ischemic damage to brain tissue evolves over time and with an uneven spatial distribution. Early irreversible changes occur in the ischemic core, whereas, in the penumbra, which receives more collateral blood flow, the damage is more mild and delayed. A better characterization of the penumbra, irreversibly damaged and healthy tissues is needed to understand the mechanisms involved in tissue death. MRSI is a powerful tool for this task if the scan time can be decreased whilst maintaining high sensitivity. Therefore, we made improvements to a ¹H MRSI protocol to study middle cerebral artery occlusion in mice. The spatial distribution of changes in the neurochemical profile was investigated, with an effective spatial resolution of 1.4 μL, applying the protocol on a 14.1‐T magnet. The acquired maps included the difficult‐to‐separate glutamate and glutamine resonances and, to our knowledge, the first mapping of metabolites γ‐aminobutyric acid and glutathione in vivo, within a metabolite measurement time of 45 min. The maps were in excellent agreement with findings from single‐voxel spectroscopy and offer spatial information at a scan time acceptable for most animal models. The metabolites measured differed with respect to the temporal evolution of their concentrations and the localization of these changes. Specifically, lactate and N‐acetylaspartate concentration changes largely overlapped with the T₂‐hyperintense region visualized with MRI, whereas changes in cholines and glutathione affected the entire middle cerebral artery territory. Glutamine maps showed elevated levels in the ischemic striatum until 8 h after reperfusion, and until 24 h in cortical tissue, indicating differences in excitotoxic effects and secondary energy failure in these tissue types. Copyright © 2011 John Wiley & Sons, Ltd.     

Simultaneous bilateral hip joint imaging at 7 Tesla using fast transmit B(1) shimming methods and multichannel transmission - a feasibility study

The objective of this study was to demonstrate the feasibility of simultaneous bilateral hip imaging at 7 Tesla. Hip joint MRI becomes clinically critical since recent advances have made hip arthroscopy an efficacious approach to treat a variety of early hip diseases. The success of these treatments requires a reliable and accurate diagnosis of intraarticular abnormalities at an early stage. Articular cartilage assessment is especially important to guide surgical decisions but is difficult to achieve with current MR methods. Because of gains in tissue contrast and spatial resolution reported at ultra high magnetic fields, there are strong expectations that imaging the hip joint at 7 Tesla will improve diagnostic accuracy. Furthermore, there is growing evidence that the majority of these hip abnormalities occur bilaterally, emphasizing the need for bilateral imaging. However, obtaining high quality images in the human torso, in particular of both hips simultaneously, must overcome a major challenge arising from the damped traveling wave behaviour of RF waves at 7 Tesla that leads to severe inhomogeneities in transmit B1 (B₁⁺) phase and magnitude, typically resulting in areas of low signal and contrast, and consequently impairing use for clinical applications. To overcome this problem, a 16‐channel stripline transceiver RF coil was used, together with a B1 shimming algorithm aiming at maximizing B₁⁺ in six regions of interest over the hips that were identified on axial scout images. Our successful results demonstrate that this approach effectively reduces inhomogeneities observed before B1 shimming and provides high joint tissue contrast in both hips while reducing the required RF power. Critical to this success was a fast small flip angle B₁⁺ calibration scan that permitted the computation of subject‐specific B1 shimming solutions, a necessary step to account for large spatial variations in B₁⁺ phase observed in different subjects. Copyright © 2012 John Wiley & Sons, Ltd.     

19 F MRSI of capecitabine in the liver at 7 T using broadband transmit–receive antennas and dual‐band RF pulses

Capecitabine (Cap) is an often prescribed chemotherapeutic agent, successfully used to cure some patients from cancer or reduce tumor burden for palliative care. However, the efficacy of the drug is limited, it is not known in advance who will respond to the drug and it can come with severe toxicity. ¹⁹ F Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) have been used to non‐invasively study Cap metabolism in vivo to find a marker for personalized treatment. In vivo detection, however, is hampered by low concentrations and the use of radiofrequency (RF) surface coils limiting spatial coverage. In this work, the use of a 7T MR system with radiative multi‐channel transmit–receive antennas was investigated with the aim of maximizing the sensitivity and spatial coverage of ¹⁹ F detection protocols. The antennas were broadband optimized to facilitate both the ¹H (298 MHz) and ¹⁹ F (280 MHz) frequencies for accurate shimming, imaging and signal combination. B₁⁺ simulations, phantom and noise measurements showed that more than 90% of the theoretical maximum sensitivity could be obtained when using B₁⁺ and B₁^? information provided at the ¹H frequency for the optimization of B₁⁺ and B₁^? at the ¹⁹ F frequency. Furthermore, to overcome the limits in maximum available RF power, whilst ensuring simultaneous excitation of all detectable conversion products of Cap, a dual‐band RF pulse was designed and evaluated. Finally, ¹⁹ F MRS(I) measurements were performed to detect ¹⁹ F metabolites in vitro and in vivo. In two patients, at 10 h (patient 1) and 1 h (patient 2) after Cap intake, ¹⁹ F metabolites were detected in the liver and the surrounding organs, illustrating the potential of the set‐up for in vivo detection of metabolic rates and drug distribution in the body. Copyright © 2015 John Wiley & Sons, Ltd.     

Decreased water T2 in fatty infiltrated skeletal muscles of patients with neuromuscular diseases

Quantitative imaging techniques are emerging in the field of magnetic resonance imaging of neuromuscular diseases (NMD). T₂ of water (T_2w) is considered an important imaging marker to assess acute and chronic alterations of the muscle fibers, being generally interpreted as an indicator for “disease activity” in the muscle tissue. To validate the accuracy and robustness of quantitative imaging methods, ¹H magnetic resonance spectroscopy (MRS) can be used as a gold standard. The purpose of the present work was to investigate T_2w of remaining muscle tissue in regions of higher proton density fat fraction (PDFF) in 40 patients with defined NMD using multi‐TE single‐voxel ¹H MRS. Patients underwent MR measurements on a 3 T system to perform a multi‐TE single‐voxel stimulated echo acquisition method (STEAM) MRS (TE = 11/15/20/25(/35) ms) in regions of healthy, edematous and fatty thigh muscle tissue. Muscle regions for MRS were selected based on T₂‐weighted water and fat images of a two‐echo 2D Dixon TSE. MRS results were confined to regions with qualitatively defined remaining muscle tissue without edema and high fat content, based on visual grading of the imaging data. The results showed decreased T_2w values with increasing PDFF with R² = 0.45 (p < 10^?3) (linear fit) and with R² = 0.51 (exponential fit). The observed dependence of T_2w on PDFF should be considered when using T_2w as a marker in NMD imaging and when performing single‐voxel MRS for T_2w in regions enclosing edematous, nonedematous and fatty infiltrated muscle tissue.     

Signal‐to‐noise ratio of a mouse brain 13C CryoProbe™ system in comparison with room temperature coils: spectroscopic phantom and in vivo results

MRI and MRS in small rodents demand very high sensitivity. Cryogenic transmit/receive radiofrequency probes (CryoProbes) designed for ¹H MRI of mouse brain provide an attractive option for increasing the performance of small‐animal MR systems. As the Larmor frequency of ¹³C nuclei is four times lower than that for ¹H nuclei, an even larger sensitivity improvement is expected for ¹³C applications. The aim of this work was to evaluate the performance of a prototype ¹³C CryoProbe? for mouse brain MRS. To investigate the possible gain of the ¹³C CryoProbe?, we acquired localized single‐voxel ¹³C spectra and chemical shift images of a dimethyl sulfoxide phantom with the CryoProbe?, as well as with two room temperature resonators. The cryogenically cooled resonator achieved approximately four‐fold higher signal‐to‐noise ratio in phantom tests when compared with the best‐performing room temperature coil. In addition, we present localized ¹³C spectra of mouse brain obtained with the CryoProbe?, as well as with one of the room temperature coils, demonstrating the performance in vivo. In summary, the cryogenic cooling technique significantly enhances the ¹³C signal sensitivity at 9.4 T and enables the investigation of metabolism within mouse brain. Copyright © 2014 John Wiley & Sons, Ltd.     

Optimized 31P MRS in the human brain at 7 T with a dedicated RF coil setup

The design and construction of a dedicated RF coil setup for human brain imaging (¹H) and spectroscopy (³¹P) at ultra‐high magnetic field strength (7 T) is presented. The setup is optimized for signal handling at the resonance frequencies for ¹H (297.2 MHz) and ³¹P (120.3 MHz). It consists of an eight‐channel ¹H transmit–receive head coil with multi‐transmit capabilities, and an insertable, actively detunable ³¹P birdcage (transmit–receive and transmit only), which can be combined with a seven‐channel receive‐only ³¹P array. The setup enables anatomical imaging and ³¹P studies without removal of the coil or the patient. By separating transmit and receive channels and by optimized addition of array signals with whitened singular value decomposition we can obtain a sevenfold increase in SNR of ³¹P signals in the occipital lobe of the human brain compared with the birdcage alone. These signals can be further enhanced by 30 ± 9% using the nuclear Overhauser effect by B₁‐shimmed low‐power irradiation of water protons. Together, these features enable acquisition of ³¹P MRSI at high spatial resolutions (3.0 cm³ voxel) in the occipital lobe of the human brain in clinically acceptable scan times (~15 min). © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Multi‐center reproducibility of neurochemical profiles in the human brain at 7 T

The purpose of this work was to harmonize data acquisition and post‐processing of single voxel proton MRS (¹H‐MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi‐localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations (‘subject’, ‘institute’ and ‘random’) were identified with a variance component analysis. Concentrations of 10–11 metabolites, which were corrected for T₁, T₂, magnetization transfer effects and partial volume effects, were obtained with mean Cramér–Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo‐inositol, scyllo‐inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within‐subject and system noise, except for total N‐acetylaspartate, glutamine and glutathione, which were related to differences in signal‐to‐noise ratio and in shimming performance between vendors. After multi‐center harmonization of acquisition and post‐processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with ¹H‐MRS at ultra‐high magnetic field. Copyright © 2015 John Wiley & Sons, Ltd.     

Direct in vivo measurement of glycine and the neurochemical profile in the rat medulla oblongata

The medulla oblongata (MO) contains a high density of glycinergic synapses and a particularly high concentration of glycine. The aims of this study were to measure directly in vivo the neurochemical profile, including glycine, in MO using a spin‐echo‐based ¹H MRS sequence at TE = 2.8 ms and to compare it with three other brain regions (cortex, striatum and hippocampus) in the rat. Glycine was quantified in MO at TE = 2.8 ms with a Cramér–Rao lower bound (CRLB) of approximately 5%. As a result of the relatively low level of glycine in the other three regions, the measurement of glycine was performed at TE = 20 ms, which provides a favorable J‐modulation of overlapping myo‐inositol resonance. The other 14 metabolites composing the neurochemical profile were quantified in vivo in MO with CRLBs below 25%. Absolute concentrations of metabolites in MO, such as glutamate, glutamine, γ‐aminobutyrate, taurine and glycine, were in the range of previous in vitro quantifications in tissue extracts. Compared with the other regions, MO had a three‐fold higher glycine concentration, and was characterised by reduced (p < 0.001) concentrations of glutamate (?50 ± 4%), glutamine (–54 ± 3%) and taurine (?78 ± 3%). This study suggests that the functional specialisation of distinct brain regions is reflected in the neurochemical profile. Copyright © 2010 John Wiley & Sons, Ltd.     

Regional metabolic differences in rat prefrontal cortex measured with in vivo 1H‐MRS correlate with regional histochemical differences

Many neurological/psychiatric disorders are associated with metabolic abnormalities in the brain observable with in vivo proton MRS (¹H‐MRS). The underlying molecular/cellular mechanisms and functional correlations of such metabolic alterations, however, are yet to be understood fully. The rodent prefrontal cortex (PFC) is comprised of multiple sub‐regions with distinctive cytoarchitecture and functions, providing a good model system to study the correlations among cerebral metabolism, regional cytoarchitecture and connectivity. In this study, the metabolic profiles in two voxels containing mainly the medial PFC (mPFC) and posterior part of the cingulate cortex (pCG), respectively, were measured with single‐voxel in vivo ¹H‐MRS in adult male rats. The levels of glutamine synthetase and glutamatergic synaptic proteins, including vesicular glutamate transporter 1, vesicular glutamate transporter 2 (VGLUT2) and post‐synaptic density protein 95 (PSD95), as well as the density of astrocytes, in these two regions were also compared semi‐quantitatively. It was shown that, relative to the pCG voxel, the mPFC voxel had significantly higher N‐acetyl aspartate, glutamate (Glu), glutamine (Gln), Glx (Glu + Gln), myo‐inositol and taurine levels. The VGLUT2/PSD95 levels and astrocyte density were also higher in the mPFC voxel than in the pCG voxel. Taken together, these results indicated that regional metabolic variations in the PFC of the adult male rat may reflect regional differences in the density of astrocytes and glutamatergic terminals associated with subcortical projections. The study provided a link between the Glu concentration measured with localized in vivo ¹H‐MRS and regional glutamatergic activities/connections in the rat PFC.