Long‐TE 1H MRS suggests that liver fat is more saturated than subcutaneous and visceral fat

Cross‐talk between adipose tissue and liver is disturbed in the metabolic syndrome. Moreover, the relative fatty acid composition of adipose and liver fat is poorly characterized. Long‐TE ¹H MRS can determine the unsaturation and polyunsaturation of adipose tissue. The aim of this study was to use long‐TE ¹H MRS to determine the composition of liver fat and its relation to adipose tissue composition. Sixteen subjects with increased liver fat (>5%) were recruited for the study. Using TE = 200 ms, we were able to resolve the olefinic (?CH, 5.3 ppm) and water (H₂O, 4.7 ppm) resonances in liver spectra and to obtain a repeatable estimate of liver fat unsaturation (coefficient of variation, 2.3%). With TE = 135 ms, the diallylic (?C? CH₂? C?, 2.8 ppm) resonance was detectable in subjects with a liver fat content above 15%. Long‐TE ¹H MRS was also used to determine the unsaturation in subcutaneous (n = 16) and visceral (n = 11) adipose tissue in the same subjects. Liver fat was more saturated (double bonds per fatty acid chain, 0.812 ± 0.022) than subcutaneous (double bonds per fatty acid chain, 0.862 ± 0.022, p < 0.0004) or visceral (double bonds per fatty acid chain, 0.865 ± 0.033, p < 0.0004) fat. Liver fat unsaturation correlated with subcutaneous unsaturation (R = 0.837, p < 0.0001) and visceral unsaturation (R = 0.879, p < 0.0004). The present study introduces a new noninvasive method for the assessment of the composition of liver fat. The results suggest that liver fat is more saturated than subcutaneous or visceral adipose tissue, which may be attributed to differences in de novo lipogenesis. Copyright © 2010 John Wiley & Sons, Ltd.     

Evaluation of short‐TE 1H MRSI for quantification of metabolites in the prostate

Back‐to‐back ¹H MRSI scans, using an endorectal and phased‐array coil combination, were performed on 18 low‐risk patients with prostate cancer at 3 T, employing TEs of 32 and 100 ms in order to compare metabolite visualization at each TE. Outer‐volume suppression of lipid signals was performed using regional saturation (REST) slabs and the quantification of spectra at both TEs was achieved with the quantitation using quantum estimation (QUEST) routine. Metabolite nulling experiments in an additional five patients found that there were negligible macromolecule background signals in prostate spectra at TE = 32 ms. Metabolite visibility was judged using the criterion Cramér–Rao lower bound (CRLB)/amplitude < 20%, and metabolite concentrations were corrected for relaxation effects and referenced to the data acquired in corresponding water‐unsuppressed MRSI scans. For the first time, the prostate metabolites spermine and myo‐inositol were quantified individually in vivo, together with citrate, choline and creatine. All five metabolite visibilities were higher in TE = 32 ms MRSI than in TE = 100 ms MRSI. At TE = 32 ms, citrate was visible in 99.0% of lipid‐free spectra, whereas, at TE = 100 ms, no metabolite simulation of citrate matched the in vivo peaks. Spermine, choline and creatine were visualised separately in 30.4% more spectra at TE = 32 ms than at TE = 100 ms, and myo‐inositol in 72.5% more spectra. T₂ values were calculated for spermine (53 ± 16 ms), choline (62 ± 17 ms) and myo‐inositol (90 ± 48 ms). Data from the TE = 32 ms spectra showed that the concentrations of citrate and spermine secretions were positively correlated in both the peripheral zone and central gland (R² = 0.73 and R² = 0.43, respectively), and that the citrate content was significantly higher in the former at 64 ± 22 mm than in the latter at 32 ± 16 mm (p = 0.01). However, lipid contamination at TE = 32 ms was substantial; therefore, to make clinical use of the greater visualisation of prostate metabolites at TE = 32 ms rather than at TE = 100 ms, three‐dimensional MRSI at TE = 32 ms with effective lipid suppression must be implemented. ©2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Non‐invasive detection of glycine as a biomarker of malignancy in childhood brain tumours using in‐vivo 1H MRS at 1.5 Tesla confirmed by ex‐vivo high‐resolution magic‐angle spinning NMR

Management of brain tumours in children would benefit from improved non‐invasive diagnosis, characterisation and prognostic biomarkers. Metabolite profiles derived from in‐vivo MRS have been shown to provide such information. Studies indicate that using optimum a priori information on metabolite contents in the construction of linear combination (LC) models of MR spectra leads to improved metabolite profile estimation. Glycine (Gly) is usually neglected in such models due to strong overlap with myo‐inositol (mI) and a low concentration in normal brain. However, biological studies indicate that Gly is abundant in high‐grade brain tumours. This study aimed to investigate the quantitation of Gly in paediatric brain tumours using MRS analysed by LCModel?, and its potential as a non‐invasive biomarker of malignancy. Single‐voxel MRS was performed using PRESS (TR 1500 ms, TE 30 ms/135 ms) on a 1.5 T scanner. Forty‐seven cases (18 high grade (HG), 17 low grade (LG), 12 ungraded) were retrospectively selected if both short‐TE and long‐TE MRS (n = 33) or short‐TE MRS and high‐resolution magic‐angle spinning (HRMAS) of matched surgical samples (n = 15) were available. The inclusion of Gly in LCModel? analyses led to significantly reduced fit residues for both short‐TE and long‐TE MRS (p < 0.05). The Gly concentrations estimated from short‐TE MRS were significantly correlated with the long‐TE values (R = 0.91, p < 0.001). The Gly concentration estimated by LCModel? was significantly higher in HG versus LG tumours for both short‐TE (p < 1e‐6) and long‐TE (p = 0.003) MRS. This was consistent with the HRMAS results, which showed a significantly higher normalised Gly concentration in HG tumours (p < 0.05) and a significant correlation with the normalised Gly concentration measured from short‐TE in‐vivo MRS (p < 0.05). This study suggests that glycine can be reliably detected in paediatric brain tumours using in‐vivo MRS on standard clinical scanners and that it is a promising biomarker of tumour aggressiveness. Copyright © 2009 John Wiley & Sons, Ltd.     

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.     

Ultrashort‐TE stimulated echo acquisition mode (STEAM) improves the quantification of lipids and fatty acid chain unsaturation in the human liver at 7 T

Ultrahigh‐field, whole‐body MR systems increase the signal‐to‐noise ratio (SNR) and improve the spectral resolution. Sequences with a short TE allow fast signal acquisition with low signal loss as a result of spin–spin relaxation. This is of particular importance in the liver for the precise quantification of the hepatocellular content of lipids (HCL). In this study, we introduce a spoiler Gradient‐switching Ultrashort STimulated Echo AcqUisition (GUSTEAU) sequence, which is a modified version of a stimulated echo acquisition mode (STEAM) sequence, with a minimum TE of 6 ms. With the high spectral resolution at 7 T, the efficient elimination of water sidebands and the post‐processing suppression of the water signal, we estimated the composition of fatty acids (FAs) via the detection of the olefinic lipid resonance and calculated the unsaturation index (UI) of hepatic FAs. The performance of the GUSTEAU sequence for the assessment of UI was validated against oil samples and provided excellent results in agreement with the data reported in the literature. When measuring HCL with GUSTEAU in 10 healthy volunteers, there was a high correlation between the results obtained at 7 and 3 T (R² = 0.961). The test–retest measurements yielded low coefficients of variation for HCL (4 ± 3%) and UI (11 ± 8%) when measured with the GUSTEAU sequence at 7 T. A negative correlation was found between UI and HCL (n = 10; p < 0.033). The ultrashort TE MRS sequence (GUSTEAU; TE = 6 ms) provided high repeatability for the assessment of HCL. The improved spectral resolution at 7 T with the elimination of water sidebands and the offline water subtraction also enabled an assessment of the unsaturation of FAs. This all highlights the potential use of this MRS acquisition scheme for studies of hepatic lipid composition in vivo. Copyright © 2015 John Wiley & Sons, Ltd.     

A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors

2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The ¹H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.     

Sexual dimorphism in hepatic lipids is associated with the evolution of metabolic status in mice

Ectopic lipid accumulation in the liver is implicated in metabolic disease in an age‐ and sex‐dependent manner. The role of hepatic lipids has been well established within the scope of metabolic insults in mice, but has been insufficiently characterized under standard housing conditions, where age‐related metabolic alterations are known to occur. We studied a total of 10 male and 10 female mice longitudinally. At 3, 7 and 11 months of age, non‐invasive ¹H‐magnetic resonance spectroscopy (¹H‐MRS) was used to monitor hepatic lipid content (HLC) and fatty acid composition in vivo, and glucose homeostasis was assessed with glucose and insulin challenges. At the end of the study, hepatic lipids were comprehensively characterized by nuclear magnetic resonance (NMR) and liquid chromatography‐mass spectrometric analyses of liver tissue samples. In males, HLC increased from 1.4 ± 0.1% at 3 months to 2.9 ± 0.3% at 7 months (p < 0.01) and 2.7 ± 0.3% at 11 months (p < 0.05), in correlation with fasting insulin levels (p < 0.01, r = 0.51) and parameters from the insulin tolerance test (ITT; p < 0.001, r = –0.69 versus area under the curve; p < 0.01, r = –0.57 versus blood glucose drop at 1 h post‐ITT; p < 0.01, r = 0.55 versus blood glucose at 3 h post‐ITT). The metabolic performance of females remained the same throughout the study, and HLC was higher than that of males at 3 months (2.7 ± 0.2%, p < 0.01), but comparable at 7 months (2.2 ± 0.2%) and 11 months (2.2 ± 0.1%). Strong sexual dimorphism in bioactive lipid species, including diacylglycerols (higher in males, p < 0.0001), phosphatidylinositols (higher in females, p < 0.001) and omega‐3 polyunsaturated fatty acids (higher in females, p < 0.01), was found to be in good correlation with metabolic scores at 11 months. Therefore, in mice housed under standard conditions, sex‐specific composition of bioactive lipids is associated with metabolic protection in females, whose metabolic performance was independent of hepatic cytosolic lipid content.     

Long TE PRESS and STEAM for measuring the triglyceride glycerol CH2 protons at 3 T

The glycerol methylene proton resonances (4–4.5 parts per million, ppm), which arise from the triglyceride backbone, are relevant to fat composition assessment and can be measured with proton MRS. The purpose of the presented work is to determine long TE (echo time) point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) values at 3 T to resolve the glycerol resonances from that of overlapping water. The response of the glycerol methylene protons of nine edible oils as a function of PRESS and STEAM TE (mixing time, TM = 20 ms) was investigated. In addition, high resolution NMR spectra of the oils were acquired at 16.5 T. Long TE values where J‐coupling losses were lowest were selected, namely a TE of 180 ms for PRESS (first echo time 17 ms) and a TE of 100 ms for STEAM (mixing time 20 ms). Oil olefinic (≈5.4 ppm) to glycerol ratios were calculated from the long TE spectra and correlated with 16.5 T ratios. The two techniques yielded olefinic/glycerol ratios that correlated with 16.5 T ratios (R² = 0.79 for PRESS and 0.90 for STEAM). The efficacy of the sequences in resolving the glycerol resonance from that of water was verified in vivo on tibial bone marrow of four healthy volunteers. In addition, the potential for using the glycerol methylene signal normalized to the methyl signal (≈0.9 ppm) to assess changes in free fatty acid content was demonstrated by measuring differences in spectra acquired from a triglyceride peanut oil phantom and from a phantom composed of a mixture of peanut oil and free fatty acid oleic acid.     

Detection of cancer in cervical tissue biopsies using mobile lipid resonances measured with diffusion‐weighted 1H magnetic resonance spectroscopy

The purpose of this study was to implement a diffusion‐weighted sequence for visualisation of mobile lipid resonances (MLR) using high resolution magic angle spinning (HR‐MAS) ¹H MRS and to evaluate its use in establishing differences between tissues from patients with cervical carcinoma that contain cancer from those that do not. A stimulated echo sequence with bipolar gradients was modified to allow T₁ and T₂ measurements and optimised by recording signal loss in HR‐MAS spectra as a function of gradient strength in model lipids and tissues. Diffusion coefficients, T₁ and apparent T₂ relaxation times were measured in model lipid systems. MLR profiles were characterised in relation to T₁ and apparent T₂ relaxation in human cervical cancer tissue samples. Diffusion‐weighted (DW) spectra of cervical biopsies were quantified and peak areas analysed using linear discriminant analysis (LDA). The optimised sequence reduced spectral overlap by suppressing signals originating from low molecular weight metabolites and non‐lipid contributions. Significantly improved MLR visualisation allowed visualisation of peaks at 0.9, 1.3, 1.6, 2.0, 2.3, 2.8, 4.3 and 5.3 ppm. MLR analysis of DW spectra showed at least six peaks arising from saturated and unsaturated lipids and those arising from triglycerides. Significant differences in samples containing histologically confirmed cancer were seen for peaks at 0.9 (p < 0.006), 1.3 (p < 0.04), 2.0 (p < 0.03), 2.8 (p < 0.003) and 4.3 ppm (p < 0.0002). LDA analysis of MLR peaks from DW spectra almost completely separated two clusters of cervical biopsies (cancer, ‘no‐cancer’), reflecting underlying differences in MLR composition. Generated Receiver Operating Characteristic (ROC) curves and calculated area under the curve (0.962) validated high sensitivity and specificity of the technique. Diffusion‐weighting of HR‐MAS spectroscopic sequences is a useful method for characterising MLR in cancer tissues and displays an accumulation of lipids arising during tumourigenesis and an increase in the unsaturated lipid and triglyceride peaks with respect to saturated MLR. Copyright © 2009 John Wiley & Sons, Ltd.     

Global gray and white matter metabolic changes after simian immunodeficiency virus infection in CD8‐depleted rhesus macaques: proton MRS imaging at 3 T

To test the hypotheses that global decreased neuro‐axonal integrity reflected by decreased N‐acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo‐inositol (mI), present in a CD8‐depleted rhesus macaque model of HIV‐associated neurocognitive disorders. To this end, we performed quantitative MRI and 16 × 16 × 4 multivoxel proton MRS imaging (TE/TR = 33/1400 ms) in five macaques pre‐ and 4–6 weeks post‐simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125 cm³ spatial resolution over ~35% of the brain) using linear regression. Pre‐ to post‐infection global WM NAA declined 8%: 6.6 ± 0.4 to 6.0 ± 0.5 mM (p = 0.05); GM Cho declined 20%: 1.3 ± 0.2 to 1.0 ± 0.1 mM (p < 0.003); global mI increased 11%: 5.7 ± 0.4 to 6.5 ± 0.5 mM (p < 0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response. Copyright © 2013 John Wiley & Sons, Ltd.     

Prediction of pathologic response to neoadjuvant chemotherapy in patients with breast cancer using diffusion‐weighted imaging and MRS

The aim of this study was to determine whether tumor size, MRS parameters and apparent diffusion coefficient (ADC) measurements could be applied to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Ninety patients with breast cancer (median size, 4.5 cm; range, 1.6–9.5 cm) were evaluated with single‐voxel ¹H MRS and dynamic contrast‐enhanced MRI. Diffusion‐weighted imaging was performed in 41 of these patients using a 1.5‐T scanner before and after completion of NAC. Pre‐ and post‐treatment measurements and changes in tumor size, MRS parameters [absolute and normalized total choline‐containing compound (tCho) integral and tCho signal‐to‐noise ratio (SNR)] and ADCs in pCR versus non‐pCR were compared using the nonparametric Mann–Whitney test. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of each parameter. After NAC, 30 patients (33%) showed pCR and 60 (67%) showed non‐pCR. At pretreatment, ADC was the only significant parameter in differentiating between pCR and non‐pCR [(0.83 ± 0.05) × 10^–3 versus (0.97 ± 0.14) × 10^–3 mm²/s] (p = 0.014). Post‐treatment measurements after completion of NAC and changes in tumor size (both p < 0.001), MRS parameters (p = 0.027 and p = 0.020 for absolute tCho integral, p = 0.036 and p = 0.023 for normalized tCho integral, and p = 0.032 and p = 0.061 for tCho SNR) and ADC (p = 0.003 and p < 0.001) were significantly different between the pCR and non‐pCR groups, except for changes in tCho SNR. In ROC analysis, the areas under the ROC curve (AUCs) of 0.63–0.73 were obtained for tumor size and MRS parameters. AUCs for pre‐ and post‐treatment ADC and changes in ADC were 0.75, 0.80 and 0.96, respectively. The optimal cut‐off of the percentage change in ADC for predicting pCR was 40.7%, yielding 100% sensitivity and 91% specificity. Patients with pCR showed significantly lower pretreatment ADCs than those with non‐pCR. The change in ADC after NAC was the most accurate predictor of pCR. Copyright © 2012 John Wiley & Sons, Ltd.     

The in vivo J‐difference editing MEGA‐PRESS technique for the detection of n‐3 fatty acids

In this study, we present a method for the detection of n‐3 fatty acid (n‐3 FA) signals using MRS in adipose tissue in vivo. This method (called oMEGA‐PRESS) is based on the selective detection of the CH₃ signal of n‐3 FA using the MEGA‐PRESS (MEshcher–GArwood Point‐RESolved Spectroscopy) J‐difference editing technique. We optimized the envelope shape and frequency of spectral editing pulses to minimize the spurious co‐editing and incomplete subtraction of the CH₃ signal of other FAs, which normally obscure the n‐3 FA CH₃ signal in MR spectra acquired using standard PRESS techniques. The post‐processing of the individual data scans with the phase and frequency correction before data subtraction and averaging was implemented to further improve the quality of in vivo spectra. The technique was optimized in vitro on lipid phantoms using various concentrations of n‐3 FA and examined in vivo at 3 T on 15 healthy volunteers. The proportion of n‐3 FA estimated by the oMEGA‐PRESS method in phantoms showed a highly significant linear correlation with the n‐3 FA content determined by gas chromatography. The signal attributed to n‐3 FA was observed in all subjects. Comparisons with the standard PRESS technique revealed an enhanced identification of the n‐3 FA signal using oMEGA‐PRESS. The presented method may be useful for the non‐invasive quantification of n‐3 FA in adipose tissue, and could aid in obtaining a better understanding of various aspects of n‐3 FA metabolism. Copyright © 2014 John Wiley & Sons, Ltd.     

In vivo and ex vivo evidence for ketamine-induced hyperglutamatergic activity in the cerebral cortex of the rat: Potential relevance to schizophrenia

Subanesthetic doses of ketamine, a noncompetitive N‐methyl‐D ‐aspartate (NMDA) receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in patients with schizophrenia. In the present study, in vivo ¹H‐MRS and ex vivo ¹H high‐resolution magic angle spinning (HR‐MAS) spectroscopy was used to examine the brain metabolism of rats treated with subanesthetic doses of ketamine (30 mg/kg) for 6 days. A single voxel localization sequence (PRESS, TR/TE = 4000/20 ms and NEX = 512) was used to acquire the spectra in a 30‐µl voxel positioned in the cerebral cortex (including mainly PFC) of the rats (ketamine group: n = 12; saline group: n = 12) anesthetized with isoflurane. After the in vivo ¹H‐MRS acquisition, the animals were sacrificed and the cerebral cortex tissues were extracted (ketamine group: n = 7; saline group: n = 7) for ex vivo ¹H HR‐MAS spectroscopy (CPMG sequence, 2.0‐s presaturation delay, 2.0‐s acquisition time, 128 transients and 4‐ms inter‐pulse delay) using a 500‐MHz NMR spectrometer. All proton metabolites were quantified using the LCModel. For the in vivo spectra, there was a significant increase in glutamate concentration in the cerebral cortex of the ketamine group compared with the controls (p < 0.05). For the ex vivo HR‐MAS spectra, there was a significant increase in the glutamate/total creatine ratio, and a decrease in the glutamine/total creatine and glutamine/glutamate ratios in the cerebral cortex tissue of the ketamine group compared with the controls. The results of the present study demonstrated that administration of subanesthetic doses of ketamine in the rat may exert at least part of their effect in the cerebral cortex by activation of glutamatergic neurotransmission. Copyright © 2011 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.     

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.     

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.     

MRS characterization of central neurocytomas using glycine

This study reports in vivo MRS findings in 11 patients with histologically diagnosed central neurocytomas, which are rare intraventricular tumors of neuronal origin. Single‐voxel ¹H MRS was carried out prior to surgery using a point‐resolved spectroscopy sequence with TR = 6 s, TE = 135 ms and 128 scans. In vitro high‐resolution ¹H spectroscopy was also carried out on two surgically excised samples. The striking features of the spectra from the central neurocytomas were the presence of high glycine, decreased N‐acetylaspartate, increased choline and alanine. Retrospective, blind analysis of the spectra by two independent observers correctly identified all but one central neurocytoma based on the presence of glycine. The presence of glycine and prominent choline in the ¹H MR spectrum is a characteristic feature of the central neurocytomas, and could be used to characterize and differentiate them from other brain tumors. Copyright © 2011 John Wiley & Sons, Ltd.     

Diffusion behavior of cerebral metabolites of congenital portal systemic shunt mice assessed noninvasively by diffusion‐weighted 1H magnetic resonance spectroscopy

Diffusion‐weighted ¹H‐MRS (DW‐MRS) allows for noninvasive investigation of the cellular compartmentalization of cerebral metabolites. DW‐MRS applied to the congenital portal systemic shunt (PSS) mouse brain may provide specific insight into alterations of cellular restrictions associated with PSS in humans. At 14.1 T, adult male PSS and their age‐matched healthy (Ctrl) mice were studied using DW‐MRS covering b‐values ranging from 0 to 45 ms/μm² to determine the diffusion behavior of abundant metabolites. The remarkable sensitivity and spectral resolution, in combination with very high diffusion weighting, allowed for precise measurement of the diffusion properties of endogenous N‐acetyl‐aspartate, total creatine, myo‐inositol, total choline with extension to glutamine and glutamate in mouse brains, in vivo. Most metabolites had comparable diffusion properties in PSS and Ctrl mice, suggesting that intracellular distribution space for these metabolites was not affected in the model. The slightly different diffusivity of the slow decaying component of taurine (0.015 ± 0.003 μm²/ms in PSS vs 0.021 ± 0.002 μm²/ms in Ctrl, P < 0.05) might support a cellular redistribution of taurine in the PSS mouse brain.     

In vivo T2 relaxation time measurement with echo‐time averaging

The accuracy of metabolite concentrations measured using in vivo proton (¹H) MRS is enhanced following correction for spin–spin (T₂) relaxation effects. In addition, metabolite proton T₂ relaxation times provide unique information regarding cellular environment and molecular mobility. Echo‐time (TE) averaging ¹H MRS involves the collection and averaging of multiple TE steps, which greatly simplifies resulting spectra due to the attenuation of spin‐coupled and macromolecule resonances. Given the simplified spectral appearance and inherent metabolite T₂ relaxation information, the aim of the present proof‐of‐concept study was to develop a novel data processing scheme to estimate metabolite T₂ relaxation times from TE‐averaged ¹H MRS data. Spectral simulations are used to validate the proposed TE‐averaging methods for estimating methyl proton T₂ relaxation times for N‐acetyl aspartate, total creatine, and choline‐containing compounds. The utility of the technique and its reproducibility are demonstrated using data obtained in vivo from the posterior‐occipital cortex of 10 healthy control subjects. Compared with standard methods, distinct advantages of this approach include built‐in macromolecule resonance attenuation, in vivo T₂ estimates closer to reported values when maximum TE ≈ T₂, and the potential for T₂ calculation of metabolite resonances otherwise inseparable in standard ¹H MRS spectra recorded in vivo. Copyright © 2014 John Wiley & Sons, Ltd.