Lipid suppression via double inversion recovery with symmetric frequency sweep for robust 2D‐GRAPPA‐accelerated MRSI of the brain at 7 T

This work presents a new approach for high‐resolution MRSI of the brain at 7 T in clinically feasible measurement times. Two major problems of MRSI are the long scan times for large matrix sizes and the possible spectral contamination by the transcranial lipid signal. We propose a combination of free induction decay (FID)‐MRSI with a short acquisition delay and acceleration via in‐plane two‐dimensional generalised autocalibrating partially parallel acquisition (2D‐GRAPPA) with adiabatic double inversion recovery (IR)‐based lipid suppression to allow robust high‐resolution MRSI. We performed Bloch simulations to evaluate the magnetisation pathways of lipids and metabolites, and compared the results with phantom measurements. Acceleration factors in the range 2–25 were tested in a phantom. Five volunteers were scanned to verify the value of our MRSI method in vivo. GRAPPA artefacts that cause fold‐in of transcranial lipids were suppressed via double IR, with a non‐selective symmetric frequency sweep. The use of long, low‐power inversion pulses (100 ms) reduced specific absorption rate requirements. The symmetric frequency sweep over both pulses provided good lipid suppression (>90%), in addition to a reduced loss in metabolite signal‐to‐noise ratio (SNR), compared with conventional IR suppression (52–70%). The metabolic mapping over the whole brain slice was not limited to a rectangular region of interest. 2D‐GRAPPA provided acceleration up to a factor of nine for in vivo FID‐MRSI without a substantial increase in g‐factors (<1.1). A 64 × 64 matrix can be acquired with a common repetition time of ~1.3 s in only 8 min without lipid artefacts caused by acceleration. Overall, we present a fast and robust MRSI method, using combined double IR fat suppression and 2D‐GRAPPA acceleration, which may be used in (pre)clinical studies of the brain at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Low SAR 31P (multi‐echo) spectroscopic imaging using an integrated whole‐body transmit coil at 7T

Phosphorus (³¹P) MRSI provides opportunities to monitor potential biomarkers. However, current applications of ³¹P MRS are generally restricted to relatively small volumes as small coils are used. Conventional surface coils require high energy adiabatic RF pulses to achieve flip angle homogeneity, leading to high specific absorption rates (SARs), and occupy space within the MRI bore. A birdcage coil behind the bore cover can potentially reduce the SAR constraints massively by use of conventional amplitude modulated pulses without sacrificing patient space. Here, we demonstrate that the integrated ³¹P birdcage coil setup with a high power RF amplifier at 7 T allows for low flip angle excitations with short repetition time (T_R) for fast 3D chemical shift imaging (CSI) and 3D T₁‐weighted CSI as well as high flip angle multi‐refocusing pulses, enabling multi‐echo CSI that can measure metabolite T₂, over a large field of view in the body. B₁⁺ calibration showed a variation of only 30% in maximum B₁ in four volunteers. High signal‐to‐noise ratio (SNR) MRSI was obtained in the gluteal muscle using two fast in vivo 3D spectroscopic imaging protocols, with low and high flip angles, and with multi‐echo MRSI without exceeding SAR levels. In addition, full liver MRSI was achieved within SAR constraints. The integrated ³¹P body coil allowed for fast spectroscopic imaging and successful implementation of the multi‐echo method in the body at 7 T. Moreover, no additional enclosing hardware was needed for ³¹P excitation, paving the way to include larger subjects and more space for receiver arrays. The increase in possible number of RF excitations per scan time, due to the improved B₁⁺ homogeneity and low SAR, allows SNR to be exchanged for spatial resolution in CSI and/or T₁ weighting by simply manipulating T_R and/or flip angle to detect and quantify ratios from different molecular species.     

In situ postmortem ethanol quantification in the cerebrospinal fluid by non‐water‐suppressed proton MRS

Determination of the ethanol concentration in corpses with MRS would allow a reproducible forensic assessment by which evidence is collected in a noninvasive manner. However, although MRS has been successfully used to detect ethanol in vivo, it has not been applied to postmortem ethanol quantification in situ. The present study examined the feasibility of the noninvasive measurement of the ethanol concentration in human corpses with MRS. A total of 15 corpses with suspected alcohol consumption before demise underwent examination in a 3 T whole body scanner. To address the partial overlap of the ethanol and lactate signal in the postmortem spectrum, non‐water‐suppressed single voxel spectra were recorded in the cerebrospinal fluid (CSF) of the left lateral ventricle via the metabolite cycling technique. The ethanol signals were quantified using the internal water as reference standard, as well as based on a reference signal acquired in a phantom. The measured values were compared with biochemically determined concentrations in the blood (BAC) and CSF (CSFAC). In 8 of the 15 corpses a BAC above zero was determined (range 0.03–1.68 g/kg). In all of these 8 corpses, ethanol was measured in CSF with the proposed MRS protocol. The two applied MRS calibration strategies resulted in similar concentrations. However, the MRS measurements generally overestimated the ethanol concentration by 0.09 g/kg (4%) to 0.72 g/kg (45%) as compared with the CSFAC value. The presented MRS protocol allows the measurement of ethanol in the CSF in human corpses and provides an estimation of the ethanol concentration prior to autopsy. Observed deviations from biochemically determined concentrations are mainly explained by the approximate correction of the relaxation attenuation of the ethanol signal.     

Fast data acquisition techniques in magnetic resonance spectroscopic imaging

Magnetic resonance spectroscopic imaging (MRSI) is an important technique for assessing the spatial variation of metabolites in vivo. The long scan times in MRSI limit clinical applicability due to patient discomfort, increased costs, motion artifacts, and limited protocol flexibility. Faster acquisition strategies can address these limitations and could potentially facilitate increased adoption of MRSI into routine clinical protocols with minimal addition to the current anatomical and functional acquisition protocols in terms of imaging time. Not surprisingly, a lot of effort has been devoted to the development of faster MRSI techniques that aim to capture the same underlying metabolic information (relative metabolite peak areas and spatial distribution) as obtained by conventional MRSI, in greatly reduced time. The gain in imaging time results, in some cases, in a loss of signal‐to‐noise ratio and/or in spatial and spectral blurring. This review examines the current techniques and advances in fast MRSI in two and three spatial dimensions and their applications. This review categorizes the acceleration techniques according to their strategy for acquisition of the k‐space. Techniques such as fast/turbo‐spin echo MRSI, echo‐planar spectroscopic imaging, and non‐Cartesian MRSI effectively cover the full k‐space in a more efficient manner per T_R. On the other hand, techniques such as parallel imaging and compressed sensing acquire fewer k‐space points and employ advanced reconstruction algorithms to recreate the spatial‐spectral information, which maintains statistical fidelity in test conditions (ie no statistically significant differences on voxel‐wise comparisions) with the fully sampled data. The advantages and limitations of each state‐of‐the‐art technique are reviewed in detail, concluding with a note on future directions and challenges in the field of fast spectroscopic imaging.     

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.     

Pitfalls and advantages of different strategies for the absolute quantification of N‐acetyl aspartate,creatine and choline in white and grey matter by 1H‐MRS

This study extensively investigates different strategies for the absolute quantitation of N‐acetyl aspartate, creatine and choline in white and grey matter by ¹H‐MRS at 1.5 T. The main focus of this study was to reliably estimate metabolite concentrations while reducing the scan time, which remains as one of the main problems in clinical MRS. Absolute quantitation was based on the water‐unsuppressed concentration as the internal standard. We compared strategies based on various experimental protocols and post‐processing strategies. Data were obtained from 30 control subjects using a PRESS sequence at several TE to estimate the transverse relaxation time, T₂, of the metabolites. Quantitation was performed with the algorithm QUEST using two different metabolite signal basis sets: a whole‐metabolite basis set (WhoM) and a basis set in which the singlet signals were split from the coupled signals (MSM). The basis sets were simulated in vivo for each TE used. Metabolites' T₂s were then determined by fitting the estimated signal amplitudes of the metabolites obtained at different TEs. Then the absolute concentrations (mM) of the metabolites were assessed for each subject using the estimated signal amplitudes and either the mean estimated relaxation times of all subjects (mean protocol, MP) or the T₂ estimated from the spectra derived from the same subject (individual protocol, IP). Results showed that MP represents a less time‐consuming alternative to IP in the quantitation of brain metabolites by ¹H‐MRS in both grey and white matter, with a comparable accuracy when performed by MSM. It was also shown that the acquisition time might be further reduced by using a variant of MP, although with reduced accuracy. In this variant, only one water‐suppressed and one water‐unsuppressed spectra were acquired, drastically reducing the duration of the entire MRS examination. However, statistical analysis highlights the reduced accuracy of MP when performed using WhoM, particularly at longer echo times. Copyright © 2009 John Wiley & Sons, Ltd.     

A referenceless Nyquist ghost correction workflow for echo planar imaging of hyperpolarized [1‐13C]pyruvate and [1‐13C]lactate

Single‐shot echo planar imaging (EPI), which allows an image to be acquired using a single excitation pulse, is used widely for imaging the metabolism of hyperpolarized ¹³C‐labelled metabolites in vivo as the technique is rapid and minimizes the depletion of the hyperpolarized signal. However, EPI suffers from Nyquist ghosting, which normally is corrected for by acquiring a reference scan. In a dynamic acquisition of a series of images, this results in the sacrifice of a time point if the reference scan involves a full readout train with no phase encoding. This time penalty is negligible if an integrated navigator echo is used, but at the cost of a lower signal‐to‐noise ratio (SNR) as a result of prolonged T₂* decay. We describe here a workflow for hyperpolarized ¹³C EPI that requires no reference scan. This involves the selection of a ghost‐containing background from a ¹³C image of a single metabolite at a single time point, the identification of phase correction coefficients that minimize signal in the selected area, and the application of these coefficients to images acquired at all time points and from all metabolites. The workflow was compared in phantom experiments with phase correction using a ¹³C reference scan, and yielded similar results in situations with a regular field of view (FOV), a restricted FOV and where there were multiple signal sources. When compared with alternative phase correction methods, the workflow showed an SNR benefit relative to integrated ¹³C reference echoes (>15%) or better ghost removal relative to a ¹H reference scan. The residual ghosting in a slightly de‐shimmed B₀ field was 1.6% using the proposed workflow and 3.8% using a ¹H reference scan. The workflow was implemented with a series of dynamically acquired hyperpolarized [1‐¹³C]pyruvate and [1‐¹³C]lactate images in vivo, resulting in images with no observable ghosting and which were quantitatively similar to images corrected using a ¹³C reference scan.     

Density‐weighted concentric rings k‐space trajectory for 1H magnetic resonance spectroscopic imaging at 7 T

It has been shown that density‐weighted (DW) k‐space sampling with spiral and conventional phase encoding trajectories reduces spatial side lobes in magnetic resonance spectroscopic imaging (MRSI). In this study, we propose a new concentric ring trajectory (CRT) for DW‐MRSI that samples k‐space with a density that is proportional to a spatial, isotropic Hanning window. The properties of two different DW‐CRTs were compared against a radially equidistant (RE) CRT and an echo‐planar spectroscopic imaging (EPSI) trajectory in simulations, phantoms and in vivo experiments. These experiments, conducted at 7 T with a fixed nominal voxel size and matched acquisition times, revealed that the two DW‐CRT designs improved the shape of the spatial response function by suppressing side lobes, also resulting in improved signal‐to‐noise ratio (SNR). High‐quality spectra were acquired for all trajectories from a specific region of interest in the motor cortex with an in‐plane resolution of 7.5 × 7.5 mm² in 8 min 3 s. Due to hardware limitations, high‐spatial‐resolution spectra with an in‐plane resolution of 5 × 5 mm² and an acquisition time of 12 min 48 s were acquired only for the RE and one of the DW‐CRT trajectories and not for EPSI. For all phantom and in vivo experiments, DW‐CRTs resulted in the highest SNR. The achieved in vivo spectral quality of the DW‐CRT method allowed for reliable metabolic mapping of eight metabolites including N‐acetylaspartylglutamate, γ‐aminobutyric acid and glutathione with Cramér‐Rao lower bounds below 50%, using an LCModel analysis. Finally, high‐quality metabolic mapping of a whole brain slice using DW‐CRT was achieved with a high in‐plane resolution of 5 × 5 mm² in a healthy subject. These findings demonstrate that our DW‐CRT MRSI technique can perform robustly on MRI systems and within a clinically feasible acquisition time.     

Reproducibility of serial whole‐brain MR Spectroscopic Imaging

The reproducibility of serial measurements using a volumetric proton MR Spectroscopic Imaging (MRSI) acquisition implemented at 3 Tesla and with lipid suppression by inversion‐recovery has been evaluated. Data were acquired from two subjects at five time points, and processed using fully‐automated procedures that included rigid registration between studies. These data were analyzed to determine coefficients of variance (COV) for each metabolite and for metabolite ratio images based on an individual voxel analysis, as well as for average and grey‐matter and white‐matter values from atlas‐defined brain regions. The volumetric MRSI acquisition was found to obtain data of sufficient quality for analysis over 70 ± 6% of the total brain volume, and spatial distributions of the resultant COV values were found to reflect the known distributions of susceptibility‐induced magnetic field inhomogeneity. Median values of the resultant voxel‐based COVs were 6.2%, 7.2%, and 9.7% for N–acetylaspartate, creatine, and choline respectively. The corresponding mean values obtained following averaging over lobar‐scale brain regions within the cerebrum were 3.5%, 3.7%, and 5.2%. These results indicate that longitudinal volumetric MRSI studies with post‐acquisition registration can provide an intra‐subject reproducibility for voxel‐based analyses that is comparable to previously‐reported single‐voxel MRS measurements, while additionally enabling increased sensitivity by averaging over larger tissue volumes. Copyright © 2009 John Wiley & Sons, Ltd.     

Noise correlations and SNR in phased‐array MRS

The acquisition of magnetic resonance spectroscopy (MRS) signals by multiple receiver coils can improve the signal‐to‐noise ratio (SNR) or alternatively can reduce the scan time maintaining a reliable SNR. However, using phased array coils in MRS studies requires efficient data processing and data combination techniques in order to exploit the sensitivity improvement of the phased array coil acquisition method. This paper describes a novel method for the combination of MRS signals acquired by phased array coils, even in presence of correlated noise between the acquisition channels. In fact, although it has been shown that electric and magnetic coupling mechanisms produce correlated noise in the coils, previous algorithms developed for MRS data combination have ignored this effect. The proposed approach takes advantage of a noise decorrelation stage to maximize the SNR of the combined spectra. In particular Principal Component Analysis (PCA) was exploited to project the acquired spectra in a subspace where the noise vectors are orthogonal. In this subspace the SNR weighting method will provide the optimal overall SNR. Performance evaluation of the proposed method is carried out on simulated ¹H‐MRS signals and experimental results are obtained on phantom ¹H‐MR spectra using a commercially available 8‐element phased array coil. Noise correlations between elements were generally low due to the optimal coil design, leading to a fair SNR gain (about 0.5%) in the center of the field of view (FOV). A greater SNR improvement was found in the peripheral FOV regions. Copyright © 2009 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.     

Global brain metabolic quantification with whole‐head proton MRS at 3 T

Total N‐acetyl‐aspartate + N‐acetyl‐aspartate–glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (¹H–MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%–65% of the brain. Here we wish to demonstrate that non‐localized, whole‐head (WH) ¹H–MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 ± 8.5 years old, were recruited and underwent T₁‐weighted MRI for tissue segmentation, non‐localizing, approximately 3 min WH ¹H–MRS (T_E/T_R/T_I = 5/10 1 /940 ms) and 30 min ¹H–MR spectroscopic imaging (MRSI) (T_E/T_R = 35/2100 ms) in a 360 cm³ volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 ± 0.5, 5.5 ± 0.4 and 1.3 ± 0.2 mM, were all within 10% of the WH: 8.6 ± 1.1, 6.0 ± 1.0 and 1.3 ± 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the “brain‐only” VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 ± 0.03 (brain ≈ 30% of WH volume). Air‐tissue susceptibility‐driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non‐localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH‐¹H‐MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.     

Quantitative comparison of post‐processing methods for reduction of frequency modulation sidebands in non‐water suppression 1H MRS

Non‐water suppression MRS (NWS MRS) has several advantages. First, the unsuppressed water signal can be used as internal calibration for metabolite quantification and as a reliable frequency/phase reference for retrospective motion correction. Second, it avoids the potential artifacts caused by incomplete water suppression (WS) and extra radiofrequency deposition from WS pulses. However, the frequency modulation (FM) sidebands originating from a large water signal will distort the spectrum. Among the methods proposed to solve the problems caused by FM sidebands, post‐acquisition processing methods are superior in flexibility for general use compared with experimental methods. In this study, we propose two algorithms based on advanced matrix decomposition to remove the FM sidebands. These methods, the simultaneous diagonalization (QZ) algorithm and its subsequent variant, the simultaneously generalized Schur decomposition (SGSD) algorithm, were numerically evaluated using computer simulations. In addition, we quantitatively compared the performance of these methods and the modulus method in an in vitro experiment and in vivo NWS MRS against conventional WS data. Our results show that the proposed SGSD algorithm can reduce the FM sidebands to achieve superior estimation of concentration on three major metabolites. This method can be applied directly to spectra pre‐acquired under various experimental conditions without modifying the acquisition sequences. Copyright © 2012 John Wiley & Sons, Ltd.     

Boosting the SNR by adding a receive‐only endorectal monopole to an external antenna array for high‐resolution,T2‐weighted imaging of early‐stage cervical cancer with 7‐T MRI

The aim of this study was to investigate the signal‐to‐noise ratio (SNR) gain in early‐stage cervical cancer at ultrahigh‐field MRI (e.g. 7 T) using a combination of multiple external antennas and a single endorectal antenna. In particular, we used an endorectal monopole antenna to increase the SNR in cervical magnetic resonance imaging (MRI). This should allow high‐resolution, T₂‐weighted imaging and magnetic resonance spectroscopy (MRS) for metabolic staging, which could facilitate the local tumor status assessment. In a prospective feasibility study, five healthy female volunteers and six patients with histologically proven stage IB1–IIB cervical cancer were scanned at 7 T. We used seven external fractionated dipole antennas for transmit–receive (transceive) and an endorectally placed monopole antenna for reception only. A region of interest, containing both normal cervix and tumor tissue, was selected for the SNR measurement. Separated signal and noise measurements were obtained in the region of the cervix for each element and in the near field of the monopole antenna (radius < 30 mm) to calculate the SNR gain of the endorectal antenna in each patient. We obtained high‐resolution, T₂‐weighted images with a voxel size of 0.7 × 0.8 × 3.0 mm³. In four cases with optimal placement of the endorectal antenna (verified on the T₂‐weighted images), a mean gain of 2.2 in SNR was obtained at the overall cervix and tumor tissue area. Within a radius of 30 mm from the monopole antenna, a mean SNR gain of 3.7 was achieved in the four optimal cases. Overlap between the two different regions of the SNR calculations was around 24%. We have demonstrated that the use of an endorectal monopole antenna substantially increases the SNR of 7‐T MRI at the cervical anatomy. Combined with the intrinsically high SNR of ultrahigh‐field MRI, this gain may be employed to obtain metabolic information using MRS and to enhance spatial resolutions to assess tumor invasion.     

A pilot validation of multi‐echo based echo‐planar correlated spectroscopic imaging in human calf muscles

A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo‐planar correlated spectroscopic imaging (EP‐COSI) sequence was accomplished using two bipolar readout trains with different phase‐encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k‐space, whereas the first readout was used for the central k‐space only. The performance of this novel sequence, called multi‐echo based echo‐planar correlated spectroscopic imaging (ME‐EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3 T MRI–MRS scanner equipped with a transmit–receive extremity coil was used. Localization of the ME‐EPCOSI sequence was in good agreement with the earlier single‐readout based EP‐COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single‐voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi‐voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non‐invasive assessment of altered lipid metabolism in the pathophysiology of T2D. Copyright © 2014 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.     

Maximizing sensitivity for fast GABA edited spectroscopy in the visual cortex at 7 T

The combination of functional MRI (fMRI) and MRS is a promising approach to relate BOLD imaging to neuronal metabolism, especially at high field strength. However, typical scan times for GABA edited spectroscopy are of the order of 6‐30 min, which is long compared with functional changes observed with fMRI. The aim of this study is to reduce scan time and increase GABA sensitivity for edited spectroscopy in the human visual cortex, by enlarging the volume of activated tissue in the primary visual cortex. A dedicated setup at 7 T for combined fMRI and GABA MRS is developed. This setup consists of a half volume multi‐transmit coil with a large screen for visual cortex activation, two high density receive arrays and an optimized single‐voxel MEGA‐sLASER sequence with macromolecular suppression for signal acquisition. The coil setup performance as well as the GABA measurement speed, SNR, and stability were evaluated. A 2.2‐fold gain of the average SNR for GABA detection was obtained, as compared with a conventional 7 T setup. This was achieved by increasing the viewing angle of the participant with respect to the visual stimulus, thereby activating almost the entire primary visual cortex, allowing larger spectroscopy measurement volumes and resulting in an improved GABA SNR. Fewer than 16 signal averages, lasting 1 min 23 s in total, were needed for the GABA fit method to become stable, as demonstrated in three participants. The stability of the measurement setup was sufficient to detect GABA with an accuracy of 5%, as determined with a GABA phantom. In vivo, larger variations in GABA concentration are found: 14‐25%. Overall, the results bring functional GABA detections at a temporal resolution closer to the physiological time scale of BOLD cortex activation.     

Partitioning k‐space for cylindrical three‐dimensional rapid acquisition with relaxation enhancement imaging in the mouse brain

Three‐dimensional rapid acquisition with relaxation enhancement (RARE) scans require the assignment of each phase encode step in two dimensions to an echo in the echo train. Although this assignment is frequently made across the entire Cartesian grid, collection of only the central cylinder of k‐space by eliminating the corners in each phase encode dimension reduces the scan time by ~22% with negligible impact on image quality. The recipe for the assignment of echoes to grid points for such an acquisition is less straightforward than for the simple full Cartesian acquisition case, and has important implications for image quality. We explored several methods of partitioning k‐space—exploiting angular symmetry in one extreme or emulating a cropped Cartesian acquisition in the other—and acquired three‐dimensional RARE magnetic resonance imaging (MRI) scans of the ex vivo mouse brain. We evaluated each partitioning method for sensitivity to artifacts and then further considered strategies to minimize these through averaging or interleaving of echoes and by empirical phase correction. All scans were collected 16 at a time with multiple‐mouse MRI. Although all schemes considered could be used to generate images, the results indicate that the emulation of a standard Cartesian echo assignment, by partitioning preferentially along one dimension within the cylinder, is more robust to artifacts. Samples at the periphery of the bore showed larger phase deviations and higher sensitivity to artifacts, but images of good quality could still be obtained with an optimized acquisition protocol. A protocol for high‐resolution (40 μm) ex vivo images using this approach is presented, and has been used routinely with a success rate of 99% in over 1000 images.     

Spatio‐spectral regularization to improve magnetic resonance spectroscopic imaging quantification

Magnetic resonance spectroscopic imaging (MRSI) is a non‐invasive technique able to provide the spatial distribution of relevant biochemical compounds commonly used as biomarkers of disease. Information provided by MRSI can be used as a valuable insight for the diagnosis, treatment and follow‐up of several diseases such as cancer or neurological disorders. Obtaining accurate metabolite concentrations from in vivo MRSI signals is a crucial requirement for the clinical utility of this technique. Despite the numerous publications on the topic, accurate quantification is still a challenging problem due to the low signal‐to‐noise ratio of the data, overlap of spectral lines and the presence of nuisance components. We propose a novel quantification method, which alleviates these limitations by exploiting a spatio‐spectral regularization scheme. In contrast to previous methods, the regularization terms are not expressed directly on the parameters being sought, but on appropriate transformed domains. In order to quantify all signals simultaneously in the MRSI grid, while introducing prior information, a fast proximal optimization algorithm is proposed. Experiments on synthetic MRSI data demonstrate that the error in the estimated metabolite concentrations is reduced by a mean of 41% with the proposed scheme. Results on in vivo brain MRSI data show the benefit of the proposed approach, which is able to fit overlapping peaks correctly and to capture metabolites that are missed by single‐voxel methods due to their lower concentrations. Copyright © 2016 John Wiley & Sons, Ltd.     

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

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