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.     

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.     

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.     

Coil combination of multichannel MRSI data at 7 T: MUSICAL

The goal of this study was to evaluate a new method of combining multi‐channel ¹H MRSI data by direct use of a matching imaging scan as a reference, rather than computing sensitivity maps. Seven healthy volunteers were measured on a 7‐T MR scanner using a head coil with a 32‐channel array coil for receive‐only and a volume coil for receive/transmit. The accuracy of prediction of the phase of the ¹H MRSI data with a fast imaging pre‐scan was investigated with the volume coil. The array coil ¹H MRSI data were combined using matching imaging data as coil combination weights. The signal‐to‐noise ratio (SNR), spectral quality, metabolic map quality and Cramér–Rao lower bounds were then compared with the data obtained by two standard methods, i.e. using sensitivity maps and the first free induction decay (FID) data point. Additional noise decorrelation was performed to further optimize the SNR gain. The new combination method improved significantly the SNR (+29%), overall spectral quality and visual appearance of metabolic maps, and lowered the Cramér–Rao lower bounds (?34%), compared with the combination method based on the first FID data point. The results were similar to those obtained by the combination method using sensitivity maps, but the new method increased the SNR slightly (+1.7%), decreased the algorithm complexity, required no reference coil and pre‐phased all spectra correctly prior to spectral processing. Noise decorrelation further increased the SNR by 13%. The proposed method is a fast, robust and simple way to improve the coil combination in ¹H MRSI of the human brain at 7 T, and could be extended to other ¹H MRSI techniques. © 2013 The Authors. NMR in Biomedicine published by 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.     

Classification of prostatic diseases by means of multivariate analysis on in vivo proton MRSI and DCE‐MRI data

Multivariate analysis has been applied on proton magnetic resonance spectroscopic imaging (¹H‐MRSI) and dynamic contrast enhanced MRI (DCE‐MRI) data of patients with different prostatic diseases such as chronic inflammation, fibrosis and adenocarcinoma. Multivariate analysis offers a global view of the entire range of information coming from both the imaging and spectroscopic side of NMR technology, leading to an integrated picture of the system relying upon the entire metabolic and dynamic profile of the studied samples. In this study, we show how this approach, applied to ¹H‐MRSI/DCE‐MRI results, allows us to differentiate among the various prostatic diseases in a non‐invasive way with a 100% accuracy. These findings suggest that multivariate analysis of ¹H‐MRSI/DCE‐MRI can significantly improve the diagnostic accuracy for these pathological entities. From a more theoretical point of view, the complementation of a single biomarker approach with an integrated picture of the entire metabolic and dynamic profile allows for a more realistic appreciation of pathological entities. Copyright © 2009 John Wiley & Sons, Ltd.     

Delineation of gliomas using radial metabolite indexing

¹H MRSI has demonstrated the ability to characterise and delineate brain tumours, but robust data analysis methods are still needed. In this study, we present an objective analysis method for MRSI data to delineate tumour abnormality regions. The presented method is a development of the choline‐to‐N‐acetylaspartate index (CNI), which uses perpendicular distances in a choline versus N‐acetylaspartate plot as a measure of abnormality. We propose a radial CNI (rCNI) method that uses the choline to N‐acetylaspartate ratio directly as an abnormality measure. To avoid problems with small or zero denominators, we perform an arctangent transformation. CNI abnormality contours were evaluated using a z‐score threshold of 2 (CNI2) and 2.5 (CNI2.5) and compared with rCNI2. Simulations modelling low‐grade (LGG) and high‐grade (HGG) gliomas with different tissue compartments and partial volume effects suggest improved specificity of rCNI2 (LGG 92%/HGG 91%) over CNI2 (LGG 69%/HGG 69%) and CNI2.5 (LGG 74%/HGG 75%), whilst retaining a similar sensitivity to both CNI2 and CNI2.5. Our simulation results also confirm a previously reported increase in specificity of CNI2.5 over CNI2 with little penalty in sensitivity. The analysis of MRSI data acquired from 10 patients with low‐grade glioma at 3 T suggests a more robust delineation of the lesions using rCNI with respect to conventional imaging compared with standard CNI. Further analysis of 29 glioma datasets acquired at 1.5 T, together with previously published estimated tumour proportions, suggests that rCNI has higher sensitivity and specificity for the identification of abnormal MRSI voxels. Copyright © 2014 John Wiley & Sons, Ltd.     

7‐T MR—from research to clinical applications?

Over 20 000 MR systems are currently installed worldwide and, although the majority operate at magnetic fields of 1.5 T and below (i.e. about 70%), experience with 3‐T (in high‐field clinical diagnostic imaging and research) and 7‐T (research only) human MR scanners points to a future in functional and metabolic MR diagnostics. Complementary to previous studies, this review attempts to provide an overview of ultrahigh‐field MR research with special emphasis on emerging clinical applications at 7 T. We provide a short summary of the technical development and the current status of installed MR systems. The advantages and challenges of ultrahigh‐field MRI and MRS are discussed with special emphasis on radiofrequency inhomogeneity, relaxation times, signal‐to‐noise improvements, susceptibility effects, chemical shifts, specific absorption rate and other safety issues. In terms of applications, we focus on the topics most likely to gain significantly from 7‐T MR, i.e. brain imaging and spectroscopy and musculoskeletal imaging, but also body imaging, which is particularly challenging. Examples are given to demonstrate the advantages of susceptibility‐weighted imaging, time‐of‐flight MR angiography, high‐resolution functional MRI, ¹H and ³¹P MRSI in the human brain, sodium and functional imaging of cartilage and the first results (and artefacts) using an eight‐channel body array, suggesting future areas of research that should be intensified in order to fully explore the potential of 7‐T MR systems for use in clinical diagnosis. Copyright © 2011 John Wiley & Sons, Ltd.     

Improving the spectral resolution and spectral fitting of 1H MRSI data from human calf muscle by the SPREAD technique

Proton magnetic resonance spectroscopic imaging (¹H MRSI) has been used for the in vivo measurement of intramyocellular lipids (IMCLs) in human calf muscle for almost two decades, but the low spectral resolution between extramyocellular lipids (EMCLs) and IMCLs, partially caused by the magnetic field inhomogeneity, has hindered the accuracy of spectral fitting. The purpose of this paper was to enhance the spectral resolution of ¹H MRSI data from human calf muscle using the SPREAD (spectral resolution amelioration by deconvolution) technique and to assess the influence of improved spectral resolution on the accuracy of spectral fitting and on in vivo measurement of IMCLs. We acquired MRI and ¹H MRSI data from calf muscles of three healthy volunteers. We reconstructed spectral lineshapes of the ¹H MRSI data based on field maps and used the lineshapes to deconvolve the measured MRS spectra, thereby eliminating the line broadening caused by field inhomogeneities and improving the spectral resolution of the ¹H MRSI data. We employed Monte Carlo (MC) simulations with 200 noise realizations to measure the variations of spectral fitting parameters and used an F‐test to evaluate the significance of the differences of the variations between the spectra before SPREAD and after SPREAD. We also used Cramer–Rao lower bounds (CRLBs) to assess the improvements of spectral fitting after SPREAD. The use of SPREAD enhanced the separation between EMCL and IMCL peaks in ¹H MRSI spectra from human calf muscle. MC simulations and F‐tests showed that the use of SPREAD significantly reduced the standard deviations of the estimated IMCL peak areas (p < 10^?8), and the CRLBs were strongly reduced (by ~37%). Copyright © 2014 John Wiley & Sons, Ltd.     

Ultra-short echo time spectroscopic imaging in rats: implications for monitoring lipids in glioma gene therapy

We demonstrate the feasibility of using ultra-short echo time (TE = 2 ms) magnetic resonance spectroscopic imaging (MRSI) to detect intracranial mobile lipids in the rat brain. High-performance outer volume suppression and pre-localization were demonstrated in phantoms and by the total absence of signals arising from extra-cranial lipids in MRSI spectra from control rats. The sequence performance was tested on glioma-bearing BDIX rats. Fast-relaxing lipid signals were spatially varied within a glioma during herpes simplex virus thymidine kinase-mediated gene therapy, demonstrating the potential application of this method.     

Combined (1)H and (31)P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis

¹H MRSI has evolved as an important tool to study the onset and progression of brain damage in multiple sclerosis. Abnormal increases in total creatine, total choline and myoinositol have been noted in multiple sclerosis. However, the pathobiochemical mechanisms related to these changes are still largely unclear. The combination of ¹H MRSI and ¹H‐decoupled ³¹P MRSI can specify to what extent phosphorylated components of total creatine and total choline contribute to this increase. Combined ¹H and ³¹P MRSI data were obtained at 3 T in 22 patients with multiple sclerosis and in 23 healthy controls, and aligned with structural MRI to allow for correction for partial volume effects caused by cerebrospinal fluid and lesion load. A significant increase in total creatine was found in multiple sclerosis, and this was attributed to equal changes in the phosphorylated and unphosphorylated components. The concentrations of the putative glial markers total creatine and myoinositol in lesion‐free ¹H MRSI voxels correlated with the global lesion load. We conclude that changes in total creatine are not related to altered energy metabolism, but rather indicate gliosis. Together with the increase in myoinositol, total creatine can be considered as a biomarker for disease severity. A significant total choline increase was mainly a result of choline components not visible by ³¹P MRS. The origin of this residual choline fraction remains to be investigated. Copyright © 2010 John Wiley & Sons, Ltd.     

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

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

Requirements for static and dynamic higher order B0 shimming of the human breast at 7 T

The increased magnetic susceptibility effects at higher magnetic fields increase the demands for shimming of the B₀ field for in vivo MRI and MRS. Both static and dynamic techniques have been developed to compensate for susceptibility‐induced field inhomogeneities. In this study, we investigate the impact of and need for both static and dynamic higher order B₀ shimming of magnetic field homogeneities in clinical breast MRI at 7 T. Both global and local field variations at lipid–tissue interfaces were observed in the magnetic field using TE‐optimized B₀ mapping at 7 T. With static B₀ shimming, a field homogeneity of 39 ± 11 Hz (n = 48) was reached in a single breast using second‐order shimming. Further compensation of the residual local field inhomogeneities caused by lipid–tissue interfaces does not seem to be feasible with shallow spherical harmonic fields. For bilateral shimming, the shimming quality was significantly less at 62 ± 15 Hz (n = 22) over both breasts, even after (simulated) fourth‐order shimming. In addition, a substantial time‐dependent field instability of 30 Hz peak to peak, with significant higher order field contributions, was observed during regular breathing. In conclusion, TE‐optimized B₀ field mapping reveals substantial field variations in the lipid‐rich environment of the human breast, in both space and time. The static field variations could be partially minimized by third‐order B₀ shimming, providing sufficient lipid suppression. However, in order to fully benefit from the increased spectral dispersion at high fields, the significant magnetic field variations during breathing need to be considered. Copyright © 2014 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.     

Hierarchical non‐negative matrix factorization (hNMF): a tissue pattern differentiation method for glioblastoma multiforme diagnosis using MRSI

MRSI has shown potential in the diagnosis and prognosis of glioblastoma multiforme (GBM) brain tumors, but its use is limited by difficult data interpretation. When the analyzed MRSI data present more than two tissue patterns, conventional non‐negative matrix factorization (NMF) implementation may lead to a non‐robust estimation. The aim of this article is to introduce an effective approach for the differentiation of GBM tissue patterns using MRSI data. A hierarchical non‐negative matrix factorization (hNMF) method that can blindly separate the most important spectral sources in short‐TE ¹H MRSI data is proposed. This algorithm consists of several levels of NMF, where only two tissue patterns are computed at each level. The method is demonstrated on both simulated and in vivo short‐TE ¹H MRSI data in patients with GBM. For the in vivo study, the accuracy of the recovered spectral sources was validated using expert knowledge. Results show that hNMF is able to accurately estimate the three tissue patterns present in the tumoral and peritumoral area of a GBM, i.e. normal, tumor and necrosis, thus providing additional useful information that can help in the diagnosis of GBM. Moreover, the hNMF results can be displayed as easily interpretable maps showing the contribution of each tissue pattern to each voxel. Copyright © 2012 John Wiley & Sons, Ltd.     

Age-related metabolite changes and volume loss in the hippocampus by magnetic resonance spectroscopy and imaging

Magnetic resonance imaging (MRI) studies have produced controversial results concerning the correlation of hippocampal volume loss with increasing age. The goals in this study were: 1) to test whether levels of N-acetyl aspartate (NAA, a neuron marker) change in the hippocampus during normal aging and 2) to determine the relationship between hippocampal NAA and volume changes. Proton magnetic resonance spectroscopic imaging (1H MRSI) and MRI were used to measure hippocampal metabolites and volumes in 24 healthy adults from 36 to 85 years of age. NAA/Cho decreased by 24% (r = 0.53, p = 0.01) and NAA/Cr by 26% (r = 0.61, p < 0.005) over the age range studied, whereas Cho/Cr remained stable, implying diminished NAA levels. Hippocampal volume shrank by 20% (r = 0.64, p < 0.05). In summary, aging effects must be considered in 1H MRSI brain studies. Furthermore, because NAA is considered a marker of neurons, these results provide stronger support for neuron loss in the aging hippocampus than volume measurements by MRI alone.     

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.     

Non‐water‐suppressed short‐echo‐time magnetic resonance spectroscopic imaging using a concentric ring k‐space trajectory

Water‐suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non‐water‐suppressed MRS spectrum is used for artefact correction, reconstruction of phased‐array coil data and metabolite quantification. Here, a two‐scan metabolite‐cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short‐echo (T_E = 14 ms), two‐dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite‐cycling is counterbalanced by a time‐efficient concentric ring k‐space trajectory. To validate the technique, water‐suppressed MRSI acquisitions were also performed for comparison. The proposed non‐water‐suppressed metabolite‐cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high‐resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non‐water‐suppressed and water‐suppressed techniques. The achieved spectral quality, signal‐to‐noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in‐plane resolution of 10 × 10 mm² in 8 min and with a Cramér‐Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non‐water‐suppressed technique enabled voxel‐wise single‐scan frequency, phase and eddy current correction. These findings demonstrate that our non‐water‐suppressed metabolite‐cycling MRSI technique can perform robustly on 3 T 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.