Unedited in vivo detection and quantification of γ‐aminobutyric acid in the occipital cortex using short‐TE MRS at 3 T

Short‐TE MRS has been proposed recently as a method for the in vivo detection and quantification of γ‐aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short‐TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal‐to‐noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal‐to‐noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short‐TE MRS in the occipital cortex of 14 healthy volunteers. Short‐TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short‐TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within‐session reproducibility was assessed in the same 14 subjects using four consecutive short‐TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 ± 4.9%. This study demonstrates that, under some experimental conditions, short‐TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions. Copyright © 2013 John Wiley & Sons, Ltd.     

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.     

A comparison of 2‐hydroxyglutarate detection at 3 and 7 T with long‐TE semi‐LASER

Abnormally high levels of the ‘oncometabolite’ 2‐hydroxyglutarate (2‐HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2‐HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2‐HG detection. To combat this, several groups have proposed MRS methods at ultra‐high field (≥7 T) where theoretical increases in signal‐to‐noise ratio and spectral resolution could improve 2‐HG detection. Long echo time (long‐TE) semi‐localization by adiabatic selective refocusing (semi‐LASER) (TE = 110 ms) is a promising method for improved 2‐HG detection in vivo at either 3 or 7 T owing to the use of broad‐band adiabatic localization. Using previously published semi‐LASER methods at 3 and 7 T, this study directly compares the detectability of 2‐HG in phantoms and in vivo across nine patients. Cramér–Rao lower bounds (CRLBs) of 2‐HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild‐type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2‐HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ‐aminobutyric acid (GABA) and 2‐HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2‐HG detection using long‐TE acquisition at 7 T may allow for more rapid estimation of 2‐HG (within a few spectral averages) together with other associated metabolic markers in glioma.     

Effect of paramagnetic manganese cations on (1)H MRS of the brain

Manganese cations (Mn(2+)) can be used as an intracellular contrast agent for structural, functional and neural pathway imaging applications. However, at high concentrations, Mn(2+) is neurotoxic and may influence the concentration of (1)H MR-detectable metabolites. Furthermore, the paramagnetic Mn(2+) cations may also influence the relaxation of the metabolites under investigation. Consequently, the purpose of this study was to investigate the effect of paramagnetic Mn(2+) cations on (1)H-MR spectra of the brain using in vivo and phantom models at 4.7 T. To investigate the direct paramagnetic effects of Mn(2+) cations on the relaxation of N-acetylaspartate (NAA), creatine and choline, T(1) relaxation times of metabolite solutions, with and without 5% albumin, and containing different Mn(2+) concentrations were determined. Relaxivity values with/without 5% albumin for NAA (4.8/28.1 s(-1) mM(-1)), creatine (2.8/2.8 s(-1) mM(-1)) and choline (1.8/1.1 s(-1) mM(-1)) showed NAA to be the most sensitive metabolite to the relaxation effects of the cations. Using an in vivo optic tract tracing imaging model, we obtained two adjacent regions of interest in the superior colliculi with different water T(1) values (Mn(2+)-enhanced = 1.01 s; unenhanced = 1.14 s) 24 h after intravitreal injection of 3 microL 50 mM MnCl(2). Using phantom and in vivo water relaxation time data, we estimated the in vivo Mn(2+) concentration to be 2-8 microM. The phantom data suggest that limited metabolite relaxation effects would be expected at this concentration. Consequently, this study indicates that, in this model, the presence of Mn(2+) cations does not significantly affect (1)H-MR spectra despite possible toxic and paramagnetic effects.     

Quantification of glutamate and glutamine using constant‐time point‐resolved spectroscopy at 3 T

Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant‐time point‐resolved spectroscopy (CT‐PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time‐domain basis set was constructed taking into account metabolite T₂ relaxation times and dephasing from B₀ inhomogeneity. Metabolite concentrations were estimated by fitting the basis one‐dimensional CT‐PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom‐built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantification revealed increased Gln after 16 weeks and increased Glu after 24 weeks of vaporized ethanol exposure in ethanol‐treated compared with control rats. Without separate quantification, the signal from the combined resonances of Glu and Gln (Glx) showed an increase at both 16 and 24 weeks in ethanol‐exposed rats, precluding the determination of the independent and differential contribution of each metabolite at each time. Copyright © 2012 John Wiley & Sons, Ltd.     

Neurometabolic and structural alterations in rat brain due to acute hypobaric hypoxia: in vivo 1H MRS at 7 T

In response to hypobaric hypoxia (HH), which occurs at high altitude, the brain undergoes deleterious changes at the structural and metabolite level. In vivo T₂ weighted imaging (T2WI) and ¹H‐MRS was performed to understand the structural and metabolic changes in the hippocampus region of rat brain. Data were acquired pre‐exposure (baseline controls), immediately after exposure and subsequently at the first, fourth, seventh and 14th days post exposure at normoxia. T₂ weighted images of rat brain showed hyperintensity in the CA2/CA3 region of the hippocampus 7 d after acute HH, which persisted till 14 d, probably indicating structural changes in the hippocampus. ¹H‐MRS results showed no change in metabolite level immediately after acute HH exposure, but on the first day of normoxia the myo‐inositol level was significantly decreased, possibly due to altered astrocyte metabolism. Metabolic alterations showing an increase in choline and decrease in glutamate on the fourth day of normoxia may be seen as a process of demyelination and loss of glutamate pool respectively. On the seventh and 14th days of normoxia, decreases in N‐acetylaspartate, creatine and glutamine + glutamate were observed, which might be due to decreased viability of glutamatergic neurons. In vivo ¹H‐MRS demonstrated early neurometabolic changes prior to probable structural changes post acute HH exposure. The extension of these studies will help in early risk assessment, developing intervention and strategies for combating HH related changes. Copyright © 2014 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.     

PRESS timings for resolving 13C4‐glutamate 1H signal at 9.4 T: Demonstration in rat with uniformly labelled 13C‐glucose

MRS of ¹³C₄‐labelled glutamate (¹³C₄‐Glu) during an infusion of a carbon‐13 (¹³C)‐labelled substrate, such as uniformly labelled glucose ([U‐¹³C₆]‐Glc), provides a measure of Glc metabolism. The presented work provides a single‐shot indirect ¹³C detection technique to quantify the approximately 2.51 ppm ¹³C₄‐Glu satellite proton (¹H) peak at 9.4 T. The methodology is an optimized point‐resolved spectroscopy (PRESS) sequence that minimizes signal contamination from the strongly coupled protons of N‐acetylaspartate (NAA), which resonate at approximately 2.49 ppm. J‐coupling evolution of protons was characterized numerically and verified experimentally. A (TE₁, TE₂) combination of (20 ms, 106 ms) was found to be suitable for minimizing NAA signal in the 2.51 ppm ¹H ¹³C₄‐Glu spectral region, while retaining the ¹³C₄‐Glu ¹H satellite peak. The efficacy of the technique was verified on phantom solutions and on two rat brains in vivo during an infusion of [U‐¹³C₆]‐Glc. LCModel was employed for analysis of the in vivo spectra to quantify the 2.51 ppm ¹H ¹³C₄‐Glu signal to obtain Glu C4 fractional enrichment time courses during the infusions. Cramér‐Rao lower bounds of about 8% were obtained for the 2.51 ppm ¹³C₄‐Glu ¹H satellite peak with the optimal TE combination.     

Short-TE localised 1H MRS of the human brain at 3 T: quantification of the metabolite signals using two approaches to account for macromolecular signal contributions

The goal of this study was to validate metabolite quantification at short TE, with particular focus on how to best account for the macromolecular signal contribution. A robust, short-TE PRESS protocol is presented, which allows reliable quantification, in vivo, of metabolite signals at 3 T in human brain. Water suppression was adapted to the experimental conditions at 3 T. Metabolite signal from the parietal white matter was quantified in the time domain using QUEST (jMRUI). The increased macromolecular signal contribution at short TE was dealt with by two approaches, based on either metabolite nulling or initial signal truncation. A detailed comparison of the two approaches was made. The first used a metabolite-nulled signal, measured either individually or averaged over different subjects. The second used the total signal, metabolites and macromolecules, from a single scan. The two approaches gave similar quantification results in terms of metabolite concentrations, but differed in their precision and the number of metabolites quantified reliably. With an average metabolite-nulled baseline, a set of seven metabolites could be reliably quantified in parietal white matter under these experimental conditions: N-acetylaspartate, myo-inositol, glucose, glutamate, glutathione, creatine and choline. When initial signal truncation was used, glucose was removed from this set. The short TE (10-11 ms) facilitated quantification of glutamate. The reliable quantification of N-acetylaspartyl glutamate at 3 T proved very difficult.     

Measurement of glycine in healthy and tumorous brain by triple‐refocusing MRS at 3 T in vivo

Glycine (Gly) has been implicated in several neurological disorders, including malignant brain tumors. The precise measurement of Gly is challenging largely as a result of the spectral overlap with myo‐inositol (mI). We report a new triple‐refocusing sequence for the reliable co‐detection of Gly and mI at 3 T and for the evaluation of Gly in healthy and tumorous brain. The sequence parameters were optimized with density‐matrix simulations and phantom validation. With a total TE of 134 ms, the sequence gave complete suppression of the mI signal between 3.5 and 3.6 ppm and, consequently, well‐defined Gly (3.55 ppm) and mI (3.64 ppm) peaks. In vivo ¹H magnetic resonance spectroscopy (MRS) data were acquired from the gray matter (GM)‐dominant medial occipital and white matter (WM)‐dominant left parietal regions in six healthy subjects, and analyzed with LCModel using in‐house‐calculated basis spectra. Tissue segmentation was performed to obtain the GM and WM contents within the MRS voxels. Metabolites were quantified with reference to GM‐rich medial occipital total creatine at 8 mM. The Gly and mI concentrations were estimated to be 0.63 ± 0.05 and 8.6 ± 0.6 mM for the medial occipital and 0.34 ± 0.05 and 5.3 ± 0.8 mM for the left parietal regions, respectively. From linear regression of the metabolite estimates versus fractional GM content, the concentration ratios between pure GM and pure WM were estimated to be 2.6 and 2.1 for Gly and mI, respectively. Clinical application of the optimized sequence was performed in four subjects with brain tumor. The Gly levels in tumors were higher than those of healthy brain. Gly elevation was more extensive in a post‐contrast enhancing region than in a non‐enhancing region. The data indicate that the optimized triple‐refocusing sequence may provide reliable co‐detection of Gly and mI, and alterations of Gly in brain tumors can be precisely evaluated.     

In vivo 1H MRS of human gallbladder bile at 3 T in one and two dimensions: detection and quantification of major biliary lipids

In vitro ¹H MRS of human bile has shown potential in the diagnosis of various hepatopancreatobiliary (HPB) diseases. Previously, in vivo ¹H MRS of human bile in gallbladder using a 1.5 T scanner demonstrated the possibility of quantification of choline‐containing phospholipids (chol‐PLs). However, other lipid components such as bile acids play an important role in the pathophysiology of the HPB system. We have employed a higher magnetic field strength (3 T), and a custom‐built receive array coil, to improve the quality of in vivo ¹H MRS of human bile in the gallbladder. We obtained significant improvement in the quality of 1D spectra (17 healthy volunteers) using a respiratory‐gated PRESS sequence with well distinguished signals for total bile acids (TBAs) plus cholesterol resonating at 0.66 ppm, taurine‐conjugated bile acids (TCBAs) at 3.08 ppm, chol‐PLs at 3.22 ppm, glycine‐conjugated bile acids (GCBAs) at 3.74 ppm, and the amide proton (?NH) arising from GCBAs and TCBAs in the region 7.76–8.05 ppm. The peak areas of these signals were measured by deconvolution, and subsequently the molar concentrations of metabolites were estimated with good accuracy, except for that of TBAs plus cholesterol. The concentration of TBAs plus cholesterol was overestimated in some cases, which could be due to lipid contamination. In addition, we report the first 2D L‐COSY spectra of human gallbladder bile in vivo (obtained in 15 healthy volunteers). 2D L‐COSY spectra will be helpful in differentiating various biliary chol‐PLs in pathological conditions of the HPB system. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

T2 measurement of J-coupled metabolites in the human brain at 3T

Proton T₂ relaxation times of metabolites in the human brain were measured using point resolved spectroscopy at 3T in vivo. Four echo times (54, 112, 246 and 374 ms) were selected from numerical and phantom analyses for effective detection of the glutamate multiplet at ~ 2.35 ppm. In vivo data were obtained from medial and left occipital cortices of five healthy volunteers. The cortices contained predominantly gray and white matter, respectively. Spectra were analyzed with LCModel software using volume‐localized calculated spectra of brain metabolites. The estimate of the signal strength vs. TE was fitted to a monoexponential function for estimation of apparent T₂ (T₂^?). T₂^? was estimated to be similar between the brain regions for creatine, choline, glutamate and myo‐inositol, but significantly different for N‐acetylaspartate singlet and multiplet. T₂^?s of glutamate and myo‐inositol were measured as 181 ± 16 and 197 ± 14 ms (mean ± SD, N = 5) for medial occipital cortices, and 180 ± 12 and 196 ± 17 ms for left occipital cortices, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

Improved resolution of glutamate,glutamine and γ‐aminobutyric acid with optimized point‐resolved spectroscopy sequence timings for their simultaneous quantification at 9.4 T

Glutamine (Gln), glutamate (Glu) and γ‐aminobutyric acid (GABA) are relevant brain metabolites that can be measured with magnetic resonance spectroscopy (MRS). This work optimizes the point‐resolved spectroscopy (PRESS) sequence echo times, TE₁ and TE₂, for improved simultaneous quantification of the three metabolites at 9.4 T. Quantification was based on the proton resonances of Gln, Glu and GABA at ≈2.45, ≈2.35 and ≈2.28 ppm, respectively. Glu exhibits overlap with both Gln and GABA; in addition, the Gln peak is contaminated by signal from the strongly coupled protons of N‐acetylaspartate (NAA), which resonate at about 2.49 ppm. J‐coupling evolution of the protons was characterized numerically and verified experimentally. A {TE₁, TE₂} combination of {106 ms, 16 ms} minimized the NAA signal in the Gln spectral region, whilst retaining Gln, Glu and GABA peaks. The efficacy of the technique was verified on phantom solutions and on rat brain in vivo. LCModel was employed to analyze the in vivo spectra. The average T₂‐corrected Gln, Glu and GABA concentrations were found to be 3.39, 11.43 and 2.20 mM, respectively, assuming a total creatine concentration of 8.5 mM. LCModel Cramér–Rao lower bounds (CRLBs) for Gln, Glu and GABA were in the ranges 14–17%, 4–6% and 16–19%, respectively. The optimal TE resulted in concentrations for Gln and GABA that agreed more closely with literature concentrations compared with concentrations obtained from short‐TE spectra acquired with a {TE₁, TE₂} combination of {12 ms, 9 ms}. LCModel estimations were also evaluated with short‐TE PRESS and with the optimized long TE of {106 ms, 16 ms}, using phantom solutions of known metabolite concentrations. It was shown that concentrations estimated with LCModel can be inaccurate when combined with short‐TE PRESS, where there is peak overlap, even when low (<20%) CRLBs are reported.     

Noninvasive quantification of human brain ascorbate concentration using 1H NMR spectroscopy at 7 T

Ascorbate (Asc, vitamin C) was quantified in the human brain noninvasively using two different ¹H NMR spectroscopy methods: short‐echo time STEAM and MEGA‐PRESS homonuclear editing. Taking advantage of increased sensitivity and chemical shift dispersion at 7 T, Asc was quantified with increased reliability relative to our previous study accomplished at 4 T. Asc concentration quantified from short‐echo time spectra measured from the occipital lobe of eight healthy subjects ([Asc] = 1.1 ± 0.3 µmol/g, mean ± SD) was in excellent agreement with Asc concentration quantified from the same volume of interest using homonuclear editing ([Asc] = 1.2 ± 0.2 µmol/g). This agreement indicates that at 7 T, Asc can be reliably quantified in the human brain simultaneously with 15 other metabolites. Additional advantages of the short‐echo time approach were: shorter measurement time than homonuclear editing and minimal effect of T₂ relaxation on Asc quantification. High magnetic field was also beneficial for Asc quantification with MEGA‐PRESS because increased chemical shift dispersion enabled editing with full efficiency, which resulted in a supra‐linear gain in signal‐to‐noise ratio relative to 4 T. Copyright © 2009 John Wiley & Sons, Ltd.     

A quantitative comparison of metabolite signals as detected by in vivo MRS with ex vivo 1H HR‐MAS for childhood brain tumours

¹H MRS provides a powerful method for investigating tumour metabolism by allowing the measurement of metabolites in vivo. Recently, the technique of ¹H high‐resolution magic angle spinning (HR‐MAS) has been shown to produce high‐quality data, allowing the accurate measurement of many metabolites present in unprocessed biopsy tissue. The purpose of this study was to evaluate the agreement between the techniques of in vivo MRS and ex vivo HR‐MAS for investigating childhood brain tumours. Short‐TE (30 ms), single‐voxel, in vivo MRS was performed on 16 paediatric patients with brain tumours at 1.5 T. A frozen biopsy sample was available for each patient. HR‐MAS was performed on the biopsy samples, and metabolite quantities were determined from the MRS and HR‐MAS data using the LCModel? and TARQUIN algorithms, respectively. Linear regression was performed on the metabolite quantities to asses the agreement between MRS and HR‐MAS. Eight of the 12 metabolite quantities were found to correlate significantly (P < 0.05). The four worst correlating metabolites were aspartate, scyllo‐inositol, glycerophosphocholine and N‐acetylaspartate, and, except for glycerophosphocholine, this error was reflected in their higher Cramer–Rao lower bounds (CRLBs), suggesting that low signal‐to‐noise was the greatest source of error for these metabolites. Glycerophosphocholine had a lower CRLB implying that interference with phosphocholine and choline was the most significant source of error. The generally good agreement observed between the two techniques suggests that both MRS and HR‐MAS can be used to reliably estimate metabolite quantities in brain tumour tissue and that tumour heterogeneity and metabolite degradation do not have an important effect on the HR‐MAS metabolite profile for the tumours investigated. HR‐MAS can be used to improve the analysis and understanding of MRS data. Copyright © 2009 John Wiley & Sons, Ltd.     

Six fucose‐α(1–2) sugars and α‐fucose assigned in the human brain using in vivo two‐dimensional MRS

A growing body of literature has indicated that fucose‐α(1–2)‐galactose sugars are implicated in the molecular mechanisms that underlie neuronal development, learning and memory in the human brain. An understanding of the in vivo roles played by these terminal fucose residues has been hampered by the lack of technology to non‐invasively monitor their levels in the human brain. We have implemented in vivo two‐dimensional MRS technology to examine the human brain in a 3‐T clinical MR scanner, and report that six fucose‐α(1–2)‐galactose residues and free α‐fucose are available for inspection. Fucose‐α(1–3)‐galactose residues cannot yet be assigned using this technology as they resonate under the water resonance. This new application offers an unprecedented insight into the molecular mechanisms by which fucosylated sugars contribute to neuronal processes and how they alter during development, ageing and disease. Copyright © 2014 John Wiley & Sons, Ltd.     

Two‐dimensional spectroscopic imaging with combined free induction decay and long‐TE acquisition (FID echo spectroscopic imaging,FIDESI) for the detection of intramyocellular lipids in calf muscle at 7 T

The aim of this study was to introduce a two‐dimensional chemical shift imaging (2D CSI) sequence, with simultaneous acquisition of free induction decay (FID) and long TEs, for the detection and quantification of intramyocellular lipids (IMCLs) in the calf at 7 T. The feasibility of the new 2D CSI sequence, which acquires FID (acquisition delay, 1.3 ms) and an echo (long TE) in one measurement, was evaluated in phantoms and volunteers (n = 5): TR/TE*/TE = 800/1.3/156 ms; 48 × 48 matrix; field of view, 200 × 200 × 20 mm³; Hamming filter; no water suppression; measurement time, 22 min 2 s. The IMCL concentration and subcutaneous lipid contamination were assessed. Spectra in the tibialis anterior (TA), gastrocnemius (GM) and soleus (SOL) muscles were analyzed. The water signal from the FID acquisition was used as an internal concentration reference. In the spectra from subcutaneous adipose tissue (SUB) and bone marrow (BM), an unsaturation index (UI) of the vinyl‐H (5.3 ppm) to methyl‐CH₃ ratio, and a polyunsaturation index (pUI) of the diallylic‐H (2.77 ppm) to ‐CH₃ ratio, were calculated. Long‐TE spectra from muscles showed a simplified spectral pattern with well‐separated IMCL for several muscle groups in the same scan. The IMCL to water ratio was largest in SOL (0.66% ± 0.23%), and lower in GM (0.37% ± 0.14%) and TA (0.36% ± 0.12%). UI and pUI for SUB were 0.65 ± 0.06 and 0.18 ± 0.04, respectively, and for BM were 0.60 ± 0.16 and 0.18 ± 0.08, respectively. The new sequence, with the proposed name ‘free induction decay echo spectroscopic imaging’ (FIDESI), provides information on both specific lipid resonances and water signal from different tissues in the calf, with high spectral and spatial resolution, as well as minimal voxel bleeding and subcutaneous lipid contamination, in clinically acceptable measurement times. Copyright © 2014 John Wiley & Sons, Ltd.     

J‐refocused 1H PRESS DEPT for localized 13C MR Spectroscopy

Proton point‐resolved spectroscopy (PRESS) localization has been combined with distortionless enhanced polarization transfer (DEPT) in multinuclear MRS to overcome the signal contamination problem in image‐selected in vivo spectroscopy (ISIS)‐combined DEPT, especially for lipid detection. However, homonuclear proton scalar couplings reduce the DEPT enhancement by modifying the spin coherence distribution under J modulation during proton PRESS localization. Herein, a J‐refocused proton PRESS‐localized DEPT sequence is presented to obtain simultaneously enhanced and localized signals from a large number of metabolites by in vivo ¹³C MRS. The suppression of J modulation during PRESS and the substantial recovery of signal enhancement by J‐refocused PRESS‐localized DEPT were demonstrated theoretically by product operator formalism, numerically by the spin density matrix simulations for different scalar coupling conditions, and experimentally with a glutamate phantom at various TEs, as well as a colza oil phantom. The application of the sequence for localized detection of saturated and unsaturated fatty acids in the calf bone marrow and skeletal muscle of healthy subjects yielded high signal enhancements simultaneously obtained for all components. Copyright © 2013 John Wiley & Sons, Ltd.