Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain

In this study, ascorbate (Asc) and glutathione (GSH) concentrations were quantified noninvasively using double-edited (1)H MRS at 4 T in the occipital cortex of healthy young [age (mean ± standard deviation) = 20.4 ± 1.4 years] and elderly (age = 76.6 ± 6.1 years) human subjects. Elderly subjects had a lower GSH concentration than younger subjects (p < 0.05). The Asc concentration was not significantly associated with age. Furthermore, the lactate (Lac) concentration was higher in elderly than young subjects. Lower GSH and higher Lac concentrations are indications of defective protection against oxidative damage and impaired mitochondrial respiration. The extent to which the observed concentration differences could be associated with physiological differences and methodological artifacts is discussed. In conclusion, GSH and Asc concentrations were compared noninvasively for the first time in young vs elderly subjects.     

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.     

Noninvasive quantification of T2 and concentrations of ascorbate and glutathione in the human brain from the same double-edited spectra

The transverse relaxation times (T₂) and concentrations of Ascorbate (Asc) and glutathione (GSH) were measured from a single dataset of double‐edited spectra that were acquired at several TEs at 4 T in the human brain. Six TEs between 102 and 152 ms were utilized to calculate T₂ for the group of 12 subjects scanned five times each. Spectra measured at all six TEs were summed to quantify the concentration in each individual scan. LCModel fitting was optimized for the quantification of the Asc and GSH double‐edited spectra. When the fitted baseline was constrained to be flat, T₂ was found to be 67 ms (95% confidence interval, 50–83 ms) for GSH and ≤115 ms for Asc using the sum of spectra measured over 60 scans. The Asc and GSH concentrations quantified in each of the 60 scans were 0.62 ± 0.08 and 0.81 ± 0.11 µmol/g [mean ± standard deviation (SD), n = 60], respectively, using 10 µmol/g N‐acetylaspartate as an internal reference and assuming a constant influence of N‐acetylaspartate and antioxidant T₂ relaxation in the reference solution and in vivo. The T₂ value of GSH was measured for the first time in the human brain. The data are consistent with short T₂ for both antioxidants. These T₂ values are essential for the absolute quantification of Asc and GSH concentrations measured at long TE, and provide a critical step towards addressing assumptions about T₂, and therefore towards the quantification of concentrations without the possibility of systematic bias. Copyright © 2010 John Wiley & Sons, Ltd.     

Repeatability of 31P MRSI in the human brain at 7 T with and without the nuclear Overhauser effect

An often‐employed strategy to enhance signals in ³¹P MRS is the generation of the nuclear Overhauser effect (NOE) by saturation of the water resonance. However, NOE allegedly increases the variability of the ³¹P data, because variation is reported in NOE enhancements. This would negate the signal‐to‐noise (SNR) gain it generates. We hypothesized that the variation in NOE enhancement values is not caused by the variability in NOE itself, but is attributable to measurement uncertainties in the values used to calculate the enhancement. If true, the expected increase in SNR with NOE would improve the repeatability of ³¹P MRS measurements. To verify this hypothesis, a repeatability study of native and NOE‐enhanced ³¹P MRSI was performed in the brains of seven healthy volunteers at 7 T. The repeatability coefficient (RC) and the coefficient of variation in repeated measurements (CoV_repeat) were determined for each method, and the 95% limits of agreement (LoAs) between native and NOE‐enhanced signals were calculated. The variation between the methods, defined by the LoA, is at least as great as that predicted by the RC of each method. The sources of variation in NOE enhancements were determined using variance component analysis. In the seven metabolites with a positive NOE enhancement (nine metabolite resonances assessed), CoV_repeat improved, on average, by 15%. The LoAs could be explained by the RCs of the individual methods for the majority of the metabolites, generally confirming our hypothesis. Variation in NOE enhancement was mainly attributable to the factor repeat, but between‐voxel effects were also present for phosphoethanolamine and (glycero)phosphocholine. CoV_repeat and fitting error were strongly correlated and improved with positive NOE. Our findings generally indicate that NOE enhances the signal of metabolites, improving the repeatability of metabolite measurements. Additional variability as a result of NOE was minimal. These findings encourage the use of NOE‐enhanced ³¹P MRSI. Copyright © 2015 John Wiley & Sons, Ltd.     

In vivo magnetic resonance spectroscopy detection of combined glutamate‐glutamine in healthy upper cervical cord at 3 T

The possibility of quantifying the superimposed signal of glutamate and glutamine (Glx) and its components by ¹ H magnetic resonance spectroscopy (MRS) in the spinal cord is an exciting challenge with important clinical applications in neurological conditions. The spinal cord is a particularly difficult region of interest due to its small volume, magnetic field inhomogeneities and physiological motion. In this study, we investigated for the first time the feasibility of obtaining quantitative measurements of Glx in healthy cervical spinal cord by ¹ H MRS at 3 T. The aim of this study was to compare two commercially available MRS sequences by spectral simulations and in vivo. A short echo time (TE) point resolved spectroscopy (PRESS) with TE = 30 ms and a stimulated echo acquisition mode (STEAM) with TE = 11 ms and mixing time (TM) = 17 ms were compared for reliability of Glx fit. Data allowed us to determine sample size estimates for future clinical studies for the first time. Results showed that PRESS provided a reliable fit for Glx in all cases (Cramér Rao lower bounds < 20%) whereas no reliable Glx fits were achieved using STEAM. Neither protocol provided reliable Glu quantification. The power calculations showed that a minimum sample size of 17 subjects per group was needed to detect Glx changes of > 20% using the PRESS sequence. This study proposed a clinically feasible MRS method for Glx detection in the human cervical cord in vivo including sample sizes needed for conclusive clinical studies. Copyright © 2012 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.     

Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

Until now, the lack of a means to detect a deficiency or to measure the pharmacologic effect in the human brain in situ has been a hindrance to the development of antioxidant‐based prevention and treatment of dementia. In this study, a recently developed ¹H MRS approach was applied to quantify key human brain antioxidant concentrations throughout the course of an aggressive antioxidant‐based intervention. The concentrations of the two most abundant central nervous system chemical antioxidants, vitamin C and glutathione, were quantified noninvasively in the human occipital cortex prior to and throughout 24 h after bolus intravenous delivery of 3 g of vitamin C. Although the kinetics of the sodium‐dependent vitamin C transporter and physiologic blood vitamin C concentrations predict theoretically that brain vitamin C concentration will not increase above its homeostatically maintained level, this theory has never been tested experimentally in the living human brain. Therefore, human brain vitamin C and glutathione concentrations were quantified noninvasively using MEGA‐PRESS double‐edited ¹H MRS and LCModel. Healthy subjects (age, 19–63 years) with typical dietary consumption, who did not take vitamin supplements, fasted overnight and then reported for the measurement of baseline antioxidant concentrations. They then began controlled feeding which they adhered to until after vitamin C and glutathione concentrations had been measured at 2, 6, 10 and 24 h after receiving intravenous vitamin C. Two of the twelve studies were sham controls in which no vitamin C was administered. The main finding was that human brain vitamin C and glutathione concentrations remained constant throughout the protocol, even though blood serum vitamin C concentrations spanned from the low end of the normal range to very high. Copyright © 2010 John Wiley & Sons, Ltd.     

Detection of lactate in the striatum without contamination of macromolecules by J‐difference editing MRS at 7 T

Lactate levels are measurable by MRS and are related to neural activity. Therefore, it is of interest to accurately measure lactate levels in the basal ganglia networks. If sufficiently stable, lactate measurements may be used to investigate alterations in dopaminergic signalling in the striatum, facilitating the detection and diagnosis of metabolic deficits. The aim of this study is to provide a J‐difference editing MRS technique for the selective editing of lactate only, thus allowing the detection of lactate without contamination of overlapping macromolecules. As a validation procedure, macromolecule nulling was combined with J‐difference editing, and this was compared with J‐difference editing with a new highly selective editing pulse. The use of a high‐field (7T) MR scanner enables the application of editing pulses with very narrow bandwidth, which are selective for lactate. We show that, despite the sensitivity to B₀ offsets, the use of a highly selective editing pulse is more efficient for the detection of lactate than the combination of a broad‐band editing pulse with macromolecule nulling. Although the signal‐to‐noise ratio of uncontaminated lactate detection in healthy subjects is relatively low, this article describes the test–retest performance of lactate detection in the striatum when using highly selective J‐difference editing MRS at 7 T. The coefficient of variation, σ_w and intraclass correlation coefficients for within‐ and between‐subject differences of lactate were determined. Lactate levels in the left and right striatum were determined twice in 10 healthy volunteers. Despite the fact that the test–retest performance of lactate detection is moderate with a coefficient of variation of about 20% for lactate, these values can be used for the design of new studies comparing, for example, patient populations with healthy controls. Copyright © 2015 John Wiley & Sons, Ltd.     

Improvement of resolution for brain coupled metabolites by optimized (1)H MRS at 7T

Resolution enhancement for glutamate (Glu), glutamine (Gln) and glutathione (GSH) in the human brain by TE‐optimized point‐resolved spectroscopy (PRESS) at 7 T is reported. Sub‐TE dependences of the multiplets of Glu, Gln, GSH, γ‐aminobutyric acid (GABA) and N‐acetylaspartate (NAA) at 2.2–2.6 ppm were investigated with density matrix simulations, incorporating three‐dimensional volume localization. The numerical simulations indicated that the C4‐proton multiplets can be completely separated with (TE₁, TE₂) = (37, 63) ms, as a result of a narrowing of the multiplets and suppression of the NAA 2.5 ppm signal. Phantom experiments reproduced the signal yield and lineshape from simulations within experimental errors. In vivo tests of optimized PRESS were conducted on the prefrontal cortex of six healthy volunteers. In spectral fitting by LCModel, Cramér–Rao lower bounds (CRLBs) of Glu, Gln and GSH were 2 ± 1, 5 ± 1 and 6 ± 2 (mean ± SD), respectively. To evaluate the performance of the optimized PRESS method under identical experimental conditions, stimulated‐echo spectra were acquired with (TE, TM) = (14, 37) and (74, 68) ms. The CRLB of Glu was similar between PRESS and short‐TE stimulated‐echo acquisition mode (STEAM), but the CRLBs of Gln and GSH were lower in PRESS than in both STEAM acquisitions. Copyright © 2010 John Wiley & Sons, Ltd.     

In vivo 31P magnetic resonance spectroscopy of the human liver at 7 T: an initial experience

Phosphorus (³¹P) MRS is a powerful tool for the non‐invasive investigation of human liver metabolism. Four in vivo ³¹P localization approaches (single voxel image selected in vivo spectroscopy (3D‐ISIS), slab selective 1D‐ISIS, 2D chemical shift imaging (CSI), and 3D‐CSI) with different voxel volumes and acquisition times were demonstrated in nine healthy volunteers. Localization techniques provided comparable signal‐to‐noise ratios normalized for voxel volume and acquisition time differences, Cramer–Rao lower bounds (8.7 ± 3.3%_1D‐ISIS, 7.6 ± 2.5%_3D‐ISIS, 8.6 ± 4.2%_2D‐CSI, 10.3 ± 2.7%_3D‐CSI), and linewidths (50 ± 24 Hz_1D‐ISIS, 34 ± 10 Hz_3D‐ISIS, 33 ± 10 Hz_2D‐CSI, 34 ± 11 Hz_3D‐CSI). Longitudinal (T₁) relaxation times of human liver metabolites at 7 T were assessed by 1D‐ISIS inversion recovery in the same volunteers (n = 9). T₁ relaxation times of hepatic ³¹P metabolites at 7 T were the following: phosphorylethanolamine – 4.41 ± 1.55 s; phosphorylcholine – 3.74 ± 1.31 s; inorganic phosphate – 0.70 ± 0.33 s; glycerol 3‐phosphorylethanolamine – 6.19 ± 0.91 s; glycerol 3‐phosphorylcholine – 5.94 ± 0.73 s; γ‐adenosine triphosphate (ATP) – 0.50 ± 0.08 s; α‐ATP – 0.46 ± 0.07 s; β‐ATP – 0.56 ± 0.07 s. The improved spectral resolution at 7 T enabled separation of resonances in the phosphomonoester and phosphodiester spectral region as well as nicotinamide adenine dinucleotide and uridine diphosphoglucose signals. An additional resonance at 2.06 ppm previously assigned to phosphoenolpyruvate or phosphatidylcholine is also detectable. These are the first ³¹P metabolite relaxation time measurements at 7 T in human liver, and they will help in the exploration of new, exciting questions in metabolic research with 7 T MR. Copyright © 2014 John Wiley & Sons, Ltd.     

Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3 T

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 in studying 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. Our goal was therefore 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 consecutive sessions using a standard clinical 3 T MR scanner. Neurochemical profiles were obtained with a short‐echo (T_E = 28 ms) semi‐LASER localization sequence from a relatively small (~4 mL) voxel that covered about 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 variation (CVs) 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 bound, 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, was lower than the 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. Copyright © 2015 John Wiley & Sons, Ltd.     

Feasibility and repeatability of localized 31P‐MRS four‐angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T

Phosphorus (³¹P) MRS, combined with saturation transfer (ST), provides non‐invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T₁^app measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four‐angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra‐high‐field MR system, to accelerate the measurement of both P_i‐to‐ATP and PCr‐to‐ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth‐resolved surface coil MRS (DRESS)‐localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, P_i‐to‐ATP and PCr‐to‐ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS‐localized FAST method. The repeatability of PCr‐to‐ATP and P_i‐to‐ATP exchange rate constants, determined by the slab‐selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr‐to‐ATP metabolic flux decreased (from F_CK = 8.21 ± 1.15 mM s^?1 to F_CK = 3.86 ± 1.38 mM s^?1) and the P_i‐to‐ATP flux increased (from F_ATP = 0.43 ± 0.14 mM s^?1 to F_ATP = 0.74 ± 0.13 mM s^?1). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS‐localized FAST method at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

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.     

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.     

Sensitivity and specificity of human brain glutathione concentrations measured using short‐TE 1H MRS at 7 T

Although the MR editing techniques that have traditionally been used for the measurement of glutathione (GSH) concentrations in vivo address the problem of spectral overlap, they suffer detriments associated with inherently long TEs. The purpose of this study was to characterize the sensitivity and specificity for the quantification of GSH concentrations without editing at short TE. The approach was to measure synthetically generated changes in GSH concentrations from in vivo stimulated echo acquisition mode (STEAM) spectra after in vitro GSH spectra had been added to or subtracted from them. Spectra from five test subjects were synthetically altered to mimic changes in the GSH signal. To account for different background noise between measurements, retest spectra (from the same individuals as used to generate the altered data) and spectra from five other individuals were compared with the synthetically altered spectra to investigate the reliability of the quantification of GSH concentration. Using STEAM spectroscopy at 7 T, GSH concentration differences on the order of 20% were detected between test and retest studies, as well as between differing populations in a small sample (n = 5) with high accuracy (R² > 0.99) and certainty (p ≤ 0.01). Both increases and decreases in GSH concentration were reliably quantified with small impact on the quantification of ascorbate and γ‐aminobutyric acid. These results show the feasibility of using short‐TE ¹H MRS to measure biologically relevant changes and differences in human brain GSH concentration. Although these outcomes are specific to the experimental approach used and the spectral quality achieved, this study serves as a template for the analogous scrutiny of quantification reliability for other compounds, methodologies and spectral qualities. Copyright © 2016 John Wiley & Sons, Ltd.     

Whole‐body radiofrequency coil for 31P MRSI at 7 T

Widespread use of ultrahigh‐field ³¹P MRSI in clinical studies is hindered by the limited field of view and non‐uniform radiofrequency (RF) field obtained from surface transceivers. The non‐uniform RF field necessitates the use of high specific absorption rate (SAR)‐demanding adiabatic RF pulses, limiting the signal‐to‐noise ratio (SNR) per unit of time. Here, we demonstrate the feasibility of using a body‐sized volume RF coil at 7 T, which enables uniform excitation and ultrafast power calibration by pick‐up probes. The performance of the body coil is examined by bench tests, and phantom and in vivo measurements in a 7‐T MRI scanner. The accuracy of power calibration with pick‐up probes is analyzed at a clinical 3‐T MR system with a close to identical ¹H body coil integrated at the MR system. Finally, we demonstrate high‐quality three‐dimensional ³¹P MRSI of the human body at 7 T within 5 min of data acquisition that includes RF power calibration. Copyright © 2016 John Wiley & Sons, Ltd.     

Region‐specific changes in ascorbate concentration during rat brain development quantified by in vivo 1H NMR spectroscopy

Ascorbate (vitamin C, Asc) was quantified in vivo using short‐TE ¹H NMR spectra from a previously published study on regional and developmental changes in the neurochemical profile of the rat brain (Tkac I, Rao R, Georgieff MK, Gruetter R. Magn Reson Med. 2003; 50: 24–32). Asc concentration was quantified on postnatal days P7–P28 from three regions that are of interest in the study of neurocognitive development, i.e. the hippocampus, striatum and cerebral cortex. The previously measured ¹H NMR spectra were re‐analyzed using LCModel with the Asc spectrum included in the basis set. The Asc concentration was consistently quantified from all 110 re‐analyzed spectra with an estimated fitting error of 7% (i.e. the average Cramer–Rao lower bound). The sensitivity of Asc quantification was sufficiently high to detect regional and developmental changes in Asc concentration. The concentration of Asc was highest on P7, and decreased with age in all three brain regions (p < 0.001) in agreement with previous in vitro studies. At P10 and older postnatal ages, an inhomogeneous distribution of Asc among brain regions was detected. In addition to facilitating the quantification of this important antioxidant concentration, the inclusion of the Asc spectrum in the LCModel basis set improved the quantification accuracy of other brain metabolite concentrations in the neurochemical profile. Copyright © 2010 John Wiley & Sons, Ltd.     

In vivo MRI analysis of depth‐dependent ultrastructure in human knee cartilage at 7 T

Signal intensities of T₂‐weighted magnetic resonance images depend on the local fiber arrangement in hyaline cartilage. The aims of this study were to determine whether angle‐sensitive MRI at 7 T can be used to quantify the cartilage ultrastructure of the knee in vivo and to assess potential differences with age. Ten younger (21–30) and ten older (55–76 years old) healthy volunteers were imaged with a T₂‐weighted spin‐echo sequence in a 7 T whole‐body MRI. A “fascicle” model was assumed to describe the depth‐dependent fiber arrangement of cartilage. The R/T boundary positions between radial and transitional zones were assessed from intensity profiles in small regions of interest in the femur and tibia, and normalized to cartilage thickness using logistic curve fits. The quality of our highly resolved (0.3 × 0.3 × 1.0 mm³) MR cartilage images were high enough for quantitative analysis (goodness of fit R² = 0.91 ± 0.09). Between younger and older subjects, normalized positions of the R/T boundary, with value 0 at the bone–cartilage interface and 1 at the cartilage surface, were significantly (p < 0.05) different in femoral (0.51 ± 0.12 versus 0.41 ± 0.10), but not in tibial cartilage (0.65 ± 0.11 versus 0.57 ± 0.09, p = 0.119). Within both age groups, differences between femoral and tibial R/T boundaries were significant. Using a fascicle model and angle‐sensitive MRI, the depth‐dependent anisotropic fiber arrangement of knee cartilage could be assessed in vivo from a single 7 T MR image. The derived quantitative parameter, thickness of the radial zone, may serve as an indicator of the structural integrity of cartilage. This method may potentially be suitable to detect and monitor early osteoarthritis because the progressive disintegration of the anisotropic network is also indicative of arthritic changes in cartilage. Copyright © 2013 John Wiley & Sons, Ltd.     

Depth‐resolved surface coil MRS (DRESS)‐localized dynamic 31P‐MRS of the exercising human gastrocnemius muscle at 7 T

Dynamic ³¹P‐MRS with sufficiently high temporal resolution enables the non‐invasive evaluation of oxidative muscle metabolism through the measurement of phosphocreatine (PCr) recovery after exercise. Recently, single‐voxel localized ³¹P‐MRS was compared with surface coil localization in a dynamic fashion, and was shown to provide higher anatomical and physiological specificity. However, the relatively long TE needed for the single‐voxel localization scheme with adiabatic pulses limits the quantification of J‐coupled spin systems [e.g. adenosine triphosphate (ATP)]. Therefore, the aim of this study was to evaluate depth‐resolved surface coil MRS (DRESS) as an alternative localization method capable of free induction decay (FID) acquisition for dynamic ³¹P‐MRS at 7 T. The localization performance of the DRESS sequence was tested in a phantom. Subsequently, two dynamic examinations of plantar flexions at 25% of maximum voluntary contraction were conducted in 10 volunteers, one examination with and one without spatial localization. The DRESS slab was positioned obliquely over the gastrocnemius medialis muscle, avoiding other calf muscles. Under the same load, significant differences in PCr signal drop (31.2 ± 16.0% versus 43.3 ± 23.4%), end exercise pH (7.06 ± 0.02 versus 6.96 ± 0.11), initial recovery rate (0.24 ± 0.13 mm /s versus 0.35 ± 0.18 mm /s) and maximum oxidative flux (0.41 ± 0.14 mm /s versus 0.54 ± 0.16 mm /s) were found between the non‐localized and DRESS‐localized data, respectively. Splitting of the inorganic phosphate (Pi) signal was observed in several non‐localized datasets, but in none of the DRESS‐localized datasets. Our results suggest that the application of the DRESS localization scheme yielded good spatial selection, and provided muscle‐specific insight into oxidative metabolism, even at a relatively low exercise load. In addition, the non‐echo‐based FID acquisition allowed for reliable detection of ATP resonances, and therefore calculation of the specific maximum oxidative flux, in the gastrocnemius medialis using standard assumptions about resting ATP concentration in skeletal muscle. Copyright © 2014 John Wiley & Sons, Ltd.     

In vivo GABA T2 determination with J‐refocused echo time extension at 7 T

A method to measure the T₂ relaxation time of GABA with spectral editing techniques is proposed. Spectral editing techniques can be used to unambiguously extract signals of low concentration J‐coupled spins such as γ‐aminobutyric acid (GABA) from overlapping resonances such as creatine and macromolecules. These sequences, however, generally have fixed and relatively long echo times. Therefore, for the absolute quantification of the edited spectrum, the T₂ relaxation time must be taken into account. To measure the T₂ relaxation time, the signal intensity has to be obtained at multiple echo times. However, on a coupled spin system such as GABA this is challenging, since the signal intensity of the target resonances is modulated not only by T₂ decay but also by the J‐coupling, which strongly influences the shapes and amplitudes of the edited signals, depending on the echo time. Here, we propose to refocus the J‐modulation of the edited signal at different echo times by using chemical shift selective refocusing. In this way the echo time can be arbitrarily extended while preserving the shape of the edited signal. The method was applied in combination with the MEGA‐sLASER editing technique to measure the in vivo T₂ relaxation time of GABA (87 ± 11 ms, n = 10) and creatine (109 ± 8 ms, n = 10) at 7 T. The T₁ relaxation time of these metabolites in a single subject was also determined (GABA, 1334 ± 158 ms; Cr, 1753 ± 12 ms). The T₂ decay curve of coupled spin systems can be sampled in an arbitrary fashion without the need for signal shape correction. Furthermore, the method can be applied with any spectral editing technique. The shortest echo time of the method is limited by the echo time of the spectral editing technique. Copyright © 2013 John Wiley & Sons, Ltd.