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.     

Proton spectroscopic imaging of the human prostate at 7 T

The sensitivity of proton MR Spectroscopic Imaging (¹H‐MRSI) of the prostate can be optimized by using the high magnetic field strength of 7 T in combination with an endorectal coil. In the work described in this paper we introduce an endorectal transceiver at 7 T, validate its safety for in vivo use and apply a pulse sequence, optimized for three‐dimensional (3D) ¹H‐MRSI of the human prostate at 7 T. A transmit/receive endorectal RF coil was adapted from a commercially available 3 T endorectal receive‐only coil and validated to remain within safety guidelines for radiofrequency (RF) power deposition using numerical models, MR thermometry of phantoms, and in vivo temperature measurements. The ¹H‐MRSI pulse sequence used adiabatic slice selective refocusing pulses and frequency‐selective water and lipid suppression to selectively obtain the relevant metabolite signals from the prostate. Quantum mechanical simulations were used to adjust the inter‐pulse timing for optimal detection of the strongly coupled spin system of citrate resulting in an echo time of 56 ms. Using this endorectal transceiver and pulse sequence with slice selective adiabatic refocusing pulses, 3D ¹H‐MRSI of the human prostate is feasible at 7 T with a repetition time of 2 s. The optimized inter‐pulse timing enables the absorptive detection of resonances of spins from spermine and citrate in phase with creatine and choline. These potential tumor markers may improve the in vivo detection, localization, and assessment of prostate cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

Longitudinal absolute metabolite quantification of white and gray matter regions in healthy controls using proton MR spectroscopic imaging

The purpose of this study was to evaluate quality parameters, metabolite concentrations and concentration ratios, and to investigate the reproducibility of quantitative proton magnetic resonance spectroscopic imaging (¹H‐MRSI) of selected white and gray matter regions of healthy adults. 2D‐quantitative short‐T_E ¹H‐MRSI spectra were obtained at 1.5T from the healthy human brain. Subjects (n = 12) were scanned twice with an interval of six months. Absolute metabolite concentrations were obtained based on coil loading, taking into account differences in sensitivity of the phased‐array head coil. Spectral quality parameters, absolute metabolite concentrations, concentration ratios, and their reproducibility were determined and compared between time‐points using a repeated measures general linear model. The quality of the spectra of selected brain areas was good, as determined by a mean spectral linewidth between 4.8 and 7.3 Hz (depending on the region). No significant differences between the two time‐points were observed for spectral quality, concentrations, or concentration ratios. The mean intrasubject coefficient of variation (CoV) varied between 4.0 and 8.5% for total N‐acetylaspartate, 7.2 and 10.8% for total creatine, 5.9 and 9.8% for myo‐inositol, and 8.0 and 13.3% for choline, and remained below 20% for glutamate. CoV was generally lower when concentration ratios were considered. The study shows that longitudinal quantitative short‐T_E ¹H‐MRSI generates reproducible absolute metabolite concentrations in healthy human white and gray matter. This may serve as a background for longitudinal clinical studies in adult patients. Copyright © 2014 John Wiley & Sons, Ltd.     

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

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

Spatially matched in vivo and ex vivo MR metabolic profiles of prostate cancer – investigation of a correlation with Gleason score

MR metabolic profiling of the prostate is promising as an additional diagnostic approach to separate indolent from aggressive prostate cancer. The objective of this study was to assess the relationship between the Gleason score and the metabolic biomarker (choline + creatine + spermine)/citrate (CCS/C) measured by ex vivo high‐resolution magic angle spinning MRS (HR‐MAS MRS) and in vivo MRSI, and to evaluate the correlation between in vivo‐ and ex vivo‐measured metabolite ratios from spatially matched prostate regions. Patients (n = 13) underwent in vivo MRSI prior to radical prostatectomy. A prostate tissue slice was snap‐frozen shortly after surgery and the locations of tissue samples (n = 40) collected for ex vivo HR‐MAS were matched to in vivo MRSI voxels (n = 40). In vivo MRSI was performed on a 3T clinical MR system and ex vivo HR‐MAS on a 14.1T magnet. Relative metabolite concentrations were calculated by LCModel fitting of in vivo spectra and by peak integration of ex vivo spectra. Spearman's rank correlations (ρ) between CCS/C from in vivo and ex vivo MR spectra, and with their corresponding Gleason score, were calculated. There was a strong positive correlation between the Gleason score and CCS/C measured both in vivo and ex vivo (ρ = 0.77 and ρ = 0.69, respectively; p < 0.001), and between in vivo and ex vivo metabolite ratios from spatially matched regions (ρ = 0.67, p < 0.001). Our data indicate that MR metabolic profiling is a potentially useful tool for the assessment of cancer aggressiveness. Moreover, the good correlation between in vivo‐ and ex vivo‐measured CCS/C demonstrates that our method is able to bridge MRSI and HR‐MAS molecular analysis. Copyright © 2012 John Wiley & Sons, Ltd.     

Accelerated echo planar J‐resolved spectroscopic imaging in prostate cancer: a pilot validation of non‐linear reconstruction using total variation and maximum entropy

The overlap of metabolites is a major limitation in one‐dimensional (1D) spectral‐based single‐voxel MRS and multivoxel‐based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two‐dimensional (2D) J‐resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four‐dimensional (4D) echo planar J‐resolved spectroscopic imaging (EP‐JRESI). The goal of the present work was to validate two different non‐linear reconstruction methods independently using compressed sensing‐based 4D EP‐JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty‐two patients with PCa with a mean age of 63.8 years (range, 46–79 years) were investigated in this study. A 4D non‐uniformly undersampled (NUS) EP‐JRESI sequence was implemented on a Siemens 3‐T MRI scanner. The NUS data were reconstructed using two non‐linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non‐cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo‐inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP‐JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites. Copyright © 2015 John Wiley & Sons, Ltd.     

High-resolution mapping of human brain metabolites by free induction decay (1)H MRSI at 7 T

This work describes a new approach for high‐spatial‐resolution ¹H MRSI of the human brain at 7 T. ¹H MRSI at 7 T using conventional approaches, such as point‐resolved spectroscopy and stimulated echo acquisition mode with volume head coils, is limited by technical difficulties, including chemical shift displacement errors, B₀/B₁ inhomogeneities, a high specific absorption rate and decreased T₂ relaxation times. The method presented here is based on free induction decay acquisition with an ultrashort acquisition delay (TE*) of 1.3 ms. This allows full signal detection with negligible T₂ decay or J‐modulation. Chemical shift displacement errors were reduced to below 5% per part per million in the in‐slice direction and were eliminated in‐plane. The B₁ sensitivity was reduced significantly and further corrected using flip angle maps. Specific absorption rate requirements were well below the limit (~20 % = 0.7 W/kg). The suppression of subcutaneous lipid signals was achieved by substantially improving the point‐spread function. High‐quality metabolic mapping of five important brain metabolites was achieved with high in‐plane resolution (64 × 64 matrix with a 3.4 × 3.4 × 12 mm³ nominal voxel size) in four healthy subjects. The ultrashort TE* increased the signal‐to‐noise ratio of J‐coupled resonances, such as glutamate and myo‐inositol, several‐fold to enable the mapping of even these metabolites with high resolution. Four measurement repetitions in one healthy volunteer provided proof of the good reproducibility of this method. The high spatial resolution allowed the visualization of several anatomical structures on metabolic maps. Free induction decay MRSI is insensitive to T₂ decay, J‐modulation, B₁ inhomogeneities and chemical shift displacement errors, and overcomes specific absorption rate restrictions at ultrahigh magnetic fields. This makes it a promising method for high‐resolution ¹H MRSI at 7 T and above. Copyright © 2011 John Wiley & Sons, Ltd.     

Characterizing human adipose tissue lipids by long echo time 1H‐MRS in vivo at 1.5 Tesla: validation by gas chromatography

The aim of this study was to investigate the use of ¹H‐MRS with various echo times to characterize subcutaneous human adipose tissue (SAT) triglyceride composition and to validate the findings with fatty acid (FA) analysis of SAT biopsies by gas chromatography (GC). ¹H‐MRS spectra were acquired with a 1.5 Tesla clinical imager from the SAT of 17 healthy volunteers, with 10 undergoing SAT biopsy. Spectra were localized with PRESS and a series of echo times; 30,50,80,135,200,300 and 540 ms were acquired with TR = 3000 ms. Prior knowledge from phantom measurements was used to construct AMARES fitting models for the lipid spectra. SAT FA composition were compared with serum lipid levels and subject characteristics in 17 subjects. Long TE (135,200 ms) spectra corresponded better with the GC data than short TE (30,50 ms) spectra. TE = 135 ms was found optimal for determining diallylic content (R = 0.952, p < 0.001) and TE = 200 ms was optimal for determining olefinic content (R = 0.800, p < 0.01). The improved performance of long TE spectra is a result of an improved baseline and better peak separation, due to J‐modulation and suppression of water. The peak position of the diallylic resonance correlated with the average double bond content of polyunsatured fatty acids with R = 0.899 (p < 0.005). The apparent T₂ of the methylene resonance displayed relatively small inter‐individual variation, 88.1 ± 1.1 ms (mean ± SD). The outer methyl triplet line of ω‐3 PUFA at 1.08 ppm could be readily detected and quantitated from spectra obtained at TE = 540. The ω‐3 resonance correlated with the ω‐3 content determined by GC with R = 0.737 (p < 0.05, n = 8). Age correlated significantly with SAT diallylic content (R = 0.569, p = 0.017, n = 17), but serum lipid levels showed no apparent relation to SAT FA composition. We conclude that long TE ¹H‐MRS provides a robust non‐invasive method for characterizing adipose tissue triglycerides in vivo. Copyright © 2010 John Wiley & Sons, Ltd.     

Reliability of MRSI brain temperature mapping at 1.5 and 3 T

MRSI permits the non‐invasive mapping of brain temperature in vivo, but information regarding its reliability is lacking. We obtained MRSI data from 31 healthy male volunteers [age range, 22–40 years; mean ± standard deviation (SD), 30.5 ± 5.0 years]. Eleven subjects (age range, 23–40 years; mean ± SD, 30.5 ± 5.2 years) were invited to receive four point‐resolved spectroscopy MRSI scans on each of 3 days in both 1.5‐T (TR/TE = 1000/144 ms) and 3‐T (TR/TE = 1700/144 ms) clinical scanners; a further 20 subjects (age range, 22–40 years; mean ± SD, 30.5 ± 4.9 years) were scanned on a single occasion at 3 T. Data were fitted in the time domain to determine the water–N‐acetylaspartate chemical shift difference, from which the temperature was estimated. Temperature data were analysed using a linear mixed effects model to determine variance components and systematic temperature changes during the scanning sessions. To characterise the effects of instrumental drift on apparent MRSI brain temperature, a temperature‐controlled phantom was constructed and scanned on multiple occasions. Components of apparent in vivo temperature variability at 1.5 T/3 T caused by inter‐subject (0.18/0.17 °C), inter‐session (0.18/0.15 °C) and within‐session (0.36/0.14 °C) effects, as well as voxel‐to‐voxel variation (0.59/0.54 °C), were determined. There was a brain cooling effect during in vivo MRSI of 0.10 °C [95% confidence interval (CI): –0.110, –0.094 °C; p < 0.001] and 0.051 °C (95% CI: –0.054, –0.048 °C; p < 0.001) per scan at 1.5 T and 3 T, respectively, whereas phantom measurements revealed minimal drift in apparent MRSI temperature relative to fibre‐optic temperature measurements. The mean brain temperature at 3 T was weakly associated with aural (R = 0.55, p = 0.002) and oral (R = 0.62, p < 0.001) measurements of head temperature. In conclusion, the variability associated with MRSI brain temperature mapping was quantified. Repeatability was somewhat higher at 3 T than at 1.5 T, although subtle spatial and temporal variations in apparent temperature were demonstrated at both field strengths. Such data should assist in the efficient design of future clinical studies. © 2013 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.     

Correlation of endorectal 2D JPRESS findings with pathological Gleason scores in prostate cancer patients

To determine the metabolite ratios of (Cho + Cr)/Cit and (Cho + Cr)/Spm in patients with two ranges of pathological Gleason scores, namely (3 + 4) and (4 + 3). By using the localized two‐dimensional (2D) J‐resolved spectroscopy (JPRESS) technique, the metabolites ratios can be calculated and correlated with prostate cancer aggressiveness. A total of 24 patients who underwent endorectal 2D JPRESS between April 2006 and July 2007 were included in this study. The 2D JPRESS voxel was localized predominantly in the peripheral zone suspected for malignancy based on pathology. Using the metabolites such as total choline (Cho), creatine (Cr), spermine (Spm) and citrate (Cit), the ratios (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated. In 14 prostate cancer patients who had a final pathologic Gleason scores of i) (3 + 4 = 7, n = 7) and ii) (4 + 3 = 7, n = 7), the metabolite ratios (mean ± SD) of (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated using the 2D JPRESS spectra as follows: i) (1.48 ± 0.83) and (1.59 ± 0.73); ii) (2.90 ± 0.94) and (2.71 ± 1.47), respectively. Higher percentage of aggressive disease correlates with higher metabolites ratio. Our pilot study suggests that 2D JPRESS can be reliably evaluated in a clinical setting using an endorectal coil. In addition to the citrate ratio, the spermine ratio also correlates with pathology based Gleason score. Copyright © 2009 John Wiley & Sons, Ltd.     

Detection of fully refocused polyamine spins in prostate cancer at 7 T

¹H MRSI is often used at 1.5 or 3 T to study prostate cancer, where the ratio of choline + creatine to citrate is taken as a marker for tumour presence. Recently, the level of polyamines (mainly spermine) has been shown to improve specificity even further. However, the in vivo detection of these polyamines (at 3.1 ppm) is hampered by signal cancellation as a result of J‐coupling effects and signal overlap with choline (3.2 ppm) and creatine (3.0 ppm) resonances. At higher magnetic field strengths, the chemical shift dispersion will increase, which allows the use of very selective radiofrequency pulses to refocus J‐coupled spins. In this work, we added selective refocusing pulses to a semi‐LASER (localisation based on adiabatic selective refocusing) sequence at 7 T, and optimised the inter‐pulse timings of the sequence for fully refocused detection of spermine spins, whilst maintaining optimised detection of choline, creatine and the strongly coupled spin system of citrate. Copyright © 2010 John Wiley & Sons, Ltd.     

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.     

Adiabatic multi‐echo 31P spectroscopic imaging (AMESING) at 7 T for the measurement of transverse relaxation times and regaining of sensitivity in tissues with short T2* values

An adiabatic multi‐echo spectroscopic imaging (AMESING) sequence, used for ³¹P MRSI, with spherical k‐space sampling and compensated phase‐encoding gradients, was implemented on a whole‐body 7‐T MR system. One free induction decay (FID) and up to five symmetric echoes can be acquired with this sequence. In tissues with low T₂* and high T₂, this can theoretically lead to a potential maximum signal‐to‐noise ratio (SNR) increase of almost a factor of three, compared with a conventional FID acquisition with Ernst‐angle excitation. However, with T₂ values being, in practice, ≤400 ms, a maximum enhancement of approximately two compared with low flip Ernst‐angle excitation should be feasible. The multi‐echo sequence enables the determination of localized T₂ values, and was validated with ³¹P three‐dimensional MRSI on the calf muscle and breast of a healthy volunteer, and subsequently applied in a patient with breast cancer. The T₂ values of phosphocreatine, phosphodiesters (PDE) and inorganic phosphate in calf muscle were 193 ± 5 ms, 375 ± 44 ms and 96 ± 10 ms, respectively, and the apparent T₂ value of γ‐ATP was 25 ± 6 ms. A T₂ value of 136 ± 15 ms for inorganic phosphate was measured in glandular breast tissue of a healthy volunteer. The T₂ values of phosphomonoesters (PME) and PDE in breast cancer tissue (ductulolobular carcinoma) ranged between 170 and 210 ms, and the PME to PDE ratios were calculated to be phosphoethanolamine/glycerophosphoethanolamine = 2.7, phosphocholine/glycerophosphocholine = 1.8 and PME/PDE = 2.3. Considering the relatively short T₂* values of the metabolites in breast tissue at 7 T, the echo spacing can be short without compromising spectral resolution, whilst maximizing the sensitivity. Copyright © 2013 John Wiley & Sons, Ltd.     

A semi‐LASER,single‐voxel spectroscopic sequence with a minimal echo time of 20.1 ms in the human brain at 3 T

An optimized semi‐LASER sequence that is capable of acquiring artefact‐free data with an echo time (TE) of 20.1 ms on a standard clinical 3 T MR system was developed. Simulations were performed to determine the optimal TEs that minimize the expected Cramér‐Rao lower bound (CRLB) as proxy for quantification accuracy of metabolites. Optimized RF pulses, crusher gradients and phase cycling were used to achieve the shortest TE in a semi‐LASER sequence to date on a clinical system. Synthetic spectra were simulated using the density matrix formalism for TEs spanning from 20.1 to 220.1 ms. These simulations were used to calculate the expected CRLB for each of the 18 metabolites typically considered in ¹H MRS. High quality spectra were obtained in six healthy volunteers in the prefrontal cortex, which is known for spurious echoes due to its proximity to the paranasal sinuses, and in the parietal‐occipital cortex. Spectral transients were sufficient in quality to enable phase and frequency alignment prior to summation over all repetitions. Automated high‐quality water suppression was obtained for all voxels without manual adjustment. The shortest TE minimized the CRLB for all brain metabolites except glycine due to its overlap with myo‐inositol at this TE. It is also demonstrated that the CRLBs increase rapidly with TE for certain coupled metabolites.     

ECLIPSE utilizing gradient‐modulated offset‐independent adiabaticity (GOIA) pulses for highly selective human brain proton MRSI

A multitude of extracranial lipid suppression methods exist for proton MRSI acquisitions. Popular and emerging lipid suppression methods each have their inherent set of advantages and disadvantages related to the achievable level of lipid suppression, RF power deposition, insensitivity to B₁⁺ field and lipid T₁ heterogeneity, brain coverage, spatial selectivity, chemical shift displacement (CSD) errors and the reliability of spectroscopic data spanning the observed 0.9‐4.7 ppm band. The utility of elliptical localization with pulsed second order fields (ECLIPSE) was previously demonstrated with a greater than 100‐fold in extracranial lipid suppression and low power requirements utilizing 3 kHz bandwidth AFP pulses. Like all gradient‐based localization methods, ECLIPSE is sensitive to CSD errors, resulting in a modified metabolic profile in edge‐of‐ROI voxels. In this work, ECLIPSE is extended with 15 kHz bandwidth second order gradient‐modulated RF pulses based on the gradient offset‐independent adiabaticity (GOIA) algorithm to greatly reduce CSD and improve spatial selectivity. An adiabatic double spin‐echo ECLIPSE inner volume selection (TE = 45 ms) MRSI method and an ECLIPSE outer volume suppression (TE = 3.2 ms) FID‐MRSI method were implemented. Both GOIA‐ECLIPSE MRSI sequences provided artifact‐free metabolite spectra in vivo, with a greater than 100‐fold in lipid suppression and less than 2.6 mm in‐plane CSD and less than 3.3 mm transition width for edge‐of‐ROI voxels, representing an ~5‐fold improvement compared with the parent, nongradient‐modulated method. Despite the 5‐fold larger bandwidth, GOIA‐ECLIPSE only required a 1.9‐fold increase in RF power. The highly robust lipid suppression combined with low CSD and sharp ROI edge transitions make GOIA‐ECLIPSE an attractive alternative to commonly employed lipid suppression methods. Furthermore, the low RF power deposition demonstrates that GOIA‐ECLIPSE is very well suited for high field (≥3 T) MRSI applications.     

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.     

Which pulse sequence is optimal for myo‐inositol detection at 3T?

Optimized myo‐inositol (mI) detection is important for diagnosing and monitoring a multitude of pathological conditions of the brain. Simulations are presented in this work, performed to decide which pulse sequence has the most significant advantage in terms of improving repeatability and accuracy of mI measurements at 3T over the pulse sequence used typically in the clinic, a TE = 35 ms PRESS sequence. Five classes of pulse sequences, four previously suggested for optimized mI detection (a short TE PRESS, a Carr‐Purcell PRESS sequence, an optimized STEAM sequence, an optimized zero quantum filter), and one optimized for mI detection in this work (a single quantum filter) were compared to a standard, TE = 35 ms pulse sequence. While limiting the SNR of an acquisition to the equivalent SNR of a spectrum acquired in 5 min from an 8 cc voxel, it was found through simulations that the most repeatable mI measurements would be obtained with a Carr‐Purcell sequence. This sequence was implemented in a clinical scanner, and improved mI measurements were demonstrated in vivo. Copyright © 2008 John Wiley & Sons, Ltd.     

Comparison of reproducibility of single voxel spectroscopy and whole‐brain magnetic resonance spectroscopy imaging at 3T

To date, single voxel spectroscopy (SVS) is the most commonly used MRS technique. SVS is relatively easy to use and provides automated and immediate access to the resulting spectra. However, it is also limited in spatial coverage. A new and very promising MRS technique allows for whole‐brain MR spectroscopic imaging (WB‐MRSI) with much improved spatial resolution. Establishing the reproducibility of data obtained using SVS and WB‐MRSI is an important first step for using these techniques to evaluate longitudinal changes in metabolite concentration. The purpose of this study was to assess and directly compare the reproducibility of metabolite quantification at 3T using SVS and WB‐MRSI in ‘hand‐knob’ areas of motor cortices and hippocampi in healthy volunteers. Ten healthy adults were scanned using both SVS and WB‐MRSI on three occasions one week apart. N‐acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo‐inositol (mI) were quantified using SVS and WB‐MRSI with reference to both Cr and H₂O. The reproducibility of each technique was evaluated using the coefficient of variation (CV), and the correspondence between the two techniques was assessed using Pearson correlation analysis. The measured mean (range) intra‐subject CVs for SVS were 5.90 (2.65‐10.66)% for metabolites (i.e. NAA, Cho, mI) relative to Cr, and 8.46 (4.21‐21.07)% for metabolites (NAA, Cr, Cho, mI) relative to H₂O. The mean (range) CVs for WB‐MRSI were 7.56 (2.78‐11.41)% for metabolites relative to Cr, and 7.79 (4.57‐14.11)% for metabolites relative to H₂O. Significant positive correlations were observed between metabolites quantified using SVS and WB‐MRSI techniques when the Cr but not H₂O reference was used. The results demonstrate that reproducibilities of SVS and WB‐MRSI are similar for quantifying the four major metabolites (NAA, Cr, Cho, mI); both SVS and WB‐MRSI exhibited good reproducibility. Our findings add reference information for choosing the appropriate ¹H‐MRS technique in future studies.     

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.