Measurement of regional variation of GABA in the human brain by optimized point‐resolved spectroscopy at 7 T in vivo

The ¹H resonances of γ‐aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short‐TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point‐resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE₂) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T₁‐weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N‐acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J‐coupled spin metabolites in human brain at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.     

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

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

Improvement of resolution for brain coupled metabolites by optimized (1)H MRS at 7T

Resolution enhancement for glutamate (Glu), glutamine (Gln) and glutathione (GSH) in the human brain by TE‐optimized point‐resolved spectroscopy (PRESS) at 7 T is reported. Sub‐TE dependences of the multiplets of Glu, Gln, GSH, γ‐aminobutyric acid (GABA) and N‐acetylaspartate (NAA) at 2.2–2.6 ppm were investigated with density matrix simulations, incorporating three‐dimensional volume localization. The numerical simulations indicated that the C4‐proton multiplets can be completely separated with (TE₁, TE₂) = (37, 63) ms, as a result of a narrowing of the multiplets and suppression of the NAA 2.5 ppm signal. Phantom experiments reproduced the signal yield and lineshape from simulations within experimental errors. In vivo tests of optimized PRESS were conducted on the prefrontal cortex of six healthy volunteers. In spectral fitting by LCModel, Cramér–Rao lower bounds (CRLBs) of Glu, Gln and GSH were 2 ± 1, 5 ± 1 and 6 ± 2 (mean ± SD), respectively. To evaluate the performance of the optimized PRESS method under identical experimental conditions, stimulated‐echo spectra were acquired with (TE, TM) = (14, 37) and (74, 68) ms. The CRLB of Glu was similar between PRESS and short‐TE stimulated‐echo acquisition mode (STEAM), but the CRLBs of Gln and GSH were lower in PRESS than in both STEAM acquisitions. Copyright © 2010 John Wiley & Sons, Ltd.     

Three-dimensional arbitrary voxel shapes in spectroscopy with submillisecond TEs

A novel spectroscopic method for submillisecond TEs and three‐dimensional arbitrarily shaped voxels was developed and applied to phantom and in vivo measurements, with additional parallel excitation (PEX) implementation. A segmented spherical shell excitation trajectory was used in combination with appropriate radiofrequency weights for target selection in three dimensions. Measurements in a two‐compartment phantom realized a TE of 955 µs, excellent spectral quality and comparable signal‐to‐noise ratios between accelerated (R = 2) and nonaccelerated modes. The two‐compartment model allowed a comparison of the spectral suppression qualities of the method and, although outer volume signals were suppressed by factors of 1434 and 2246 compared with the theoretical unsuppressed case for the clinical and PEX modes, respectively, incomplete suppression of the outer volume (935 cm³ compared with a target volume of 5.86 cm³) resulted in a spectral contamination of 10.2% and 6.5% compared with the total signal. The method was also demonstrated in vivo in human brain on a clinical system at TE = 935 µs with good signal‐to‐noise ratio and spatial and spectral selection, and included LCModel relative quantification analysis. Eight metabolites showed significant fitting accuracy, including aspartate, N‐acetylaspartylglutamate, glutathione and glutamate. Copyright © 2012 John Wiley & Sons, Ltd.     

Regional distributions of brain glutamate and glutamine in normal subjects

Glutamate (Glu) and glutamine (Gln) play an important role in neuronal regulation and are of value as MRS‐observable diagnostic biomarkers. In this study the relative concentrations of these metabolites have been measured in multiple regions in the normal brain using a short‐T_E whole‐brain MRSI measurement at 3 T combined with a modified data analysis approach that used spatial averaging to obtain high‐SNR spectra from atlas‐registered anatomic regions or interest. By spectral fitting of high‐SNR spectra this approach yielded reliable measurements across a wide volume of the brain. Spectral averaging also demonstrated increased SNR and improved fitting accuracy for the sum of Glu and Gln (Glx) compared with individual voxel fitting. Results in 26 healthy controls showed relatively constant Glu/Cr and Gln/Cr throughout the cerebrum, although with increased values in the anterior cingulum and paracentral lobule, and increased Gln/Cr in the superior motor area. The deep gray‐matter regions of thalamus, putamen, and pallidum show lower Glu/Cr compared with cortical white‐matter regions. Lobar measurements demonstrated reduced Glu/Cr and Gln/Cr in the cerebellum as compared with the cerebrum, where white‐matter regions show significantly lower Glu/Cr and Gln/Cr as compared with gray‐matter regions across multiple brain lobes. Regression analysis showed no significant effect of gender on Glu/Cr or Gln/Cr measurement; however, Glx/Cr ratio was found to be significantly negatively correlated with age in some lobar brain regions. In summary, this methodology provides the spectral quality necessary for reliable separation of Glu and Gln at 3 T from a single MRSI acquisition enabling generation of regional distributions of metabolites over a large volume of the brain, including cortical regions. Copyright © 2016 John Wiley & Sons, Ltd.     

Phase‐adjusted echo time (PATE)‐averaging 1H MRS: application for improved glutamine quantification at 2.89 T

¹H MRS investigations have reported altered glutamatergic neurotransmission in a variety of psychiatric disorders. The unraveling of glutamate from glutamine resonances is crucial for the interpretation of these observations, although this remains a challenge at clinical static magnetic field strengths. Glutamate resolution can be improved through an approach known as echo time (TE) averaging, which involves the acquisition and subsequent averaging of multiple TE steps. The process of TE averaging retains the central component of the glutamate methylene multiplet at 2.35 ppm, with the simultaneous attenuation of overlapping phase‐modulated coupled resonances of glutamine and N‐acetylaspartate. We have developed a novel post‐processing approach, termed phase‐adjusted echo time (PATE) averaging, for the retrieval of glutamine signals from a TE‐averaged ¹H MRS dataset. The method works by the application of an optimal TE‐specific phase term, which is derived from spectral simulation, prior to averaging over TE space. The simulation procedures and preliminary in vivo spectra acquired from the human frontal lobe at 2.89 T are presented. Three metabolite normalization schemes were developed to evaluate the frontal lobe test–retest reliability for glutamine measurement in six subjects, and the resulting values were comparable with previous reports for within‐subject (9–14%) and inter‐subject (14–20%) measures. Using the acquisition parameters and TE range described, glutamine quantification is possible in approximately 10 min. The post‐processing methods described can also be applied retrospectively to extract glutamine and glutamate levels from previously acquired TE‐averaged ¹H MRS datasets. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

Glutamate quantification in patients with supratentorial gliomas using chemical shift imaging

This study aimed to evaluate and validate chemical shift imaging (CSI) for in vivo glutamate (Glu) quantification in patients with supratentorial gliomas. If validated, CSI could become an extremely useful tool to investigate metabolic dysfunction of Glu in excitotoxic neuropathologies. Quantitative CSI estimates of Glu concentrations were compared with known concentrations of Glu in aqueous phantom solutions. Forty‐one patients with known or likely supratentorial gliomas underwent preoperative CSI. The spectra obtained were analyzed for Glu concentrations and Glu to creatine (Cr) ratios. These in vivo measurements were correlated against ex vivo Glu content quantified by high performance liquid chromatography (HPLC) measured in 65 resected brain tumor and peritumoral brain specimens. For the phantom solutions the CSI estimates of Glu concentration and the Glu/Cr ratios were highly correlated with known Glu concentration (r² = 0.95, p = 0.002, and r² = 0.97, p < 0.0001, respectively). There was a modest, but statistically significant, correlation between the ex vivo measured Glu and in vivo spectroscopic Glu concentration (r² = 0.22, p = 0.04) and ratios of Glu to Cr (r² = 0.30, p = 0.002). Quantitative measurement of Glu content is feasible in patients with supratentorial gliomas using CSI. The in vitro and in vivo results suggest that this has the potential to be a reliable quantitative imaging assay for brain tumor patients. This may have wide clinical research applications in a number of neurological disorders where Glu excitotoxicity and metabolic dysfunction are known to play a role in pathogenesis, including tumor associated epilepsy, epilepsy, stroke and neurotrauma. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Towards a neurochemical profile of the amygdala using short‐TE 1H magnetic resonance spectroscopy at 3 T

The amygdala plays a key role in emotional learning and in the processing of emotions. As disturbed amygdala function has been linked to several psychiatric conditions, a knowledge of its biochemistry, especially neurotransmitter levels, is highly desirable. The spin echo full intensity acquired localized (SPECIAL) sequence, together with a transmit/receive coil, was used to perform very short‐TE magnetic resonance spectroscopy at 3 T to determine the neurochemical profile in a spectroscopic voxel containing the amygdala in 21 healthy adult subjects. For spectral analysis, advanced data processing was applied in combination with a macromolecule baseline measured in the anterior cingulate for spectral fitting. The concentrations of total N‐acetylaspartate, total creatine, total choline, myo‐inositol and, for the first time, glutamate were quantified with high reliability (uncertainties far below 10%). For these metabolites, the inter‐individual variability, reflected by the relative standard deviations for the cohort studied, varied between 12% (glutamate) and 22% (myo‐inositol). Glutamine and glutathione could also be determined, albeit with lower precision. Retest on four subjects showed good reproducibility. The devised method allows the determination of metabolite concentrations in the amygdala voxel, including glutamate, provides an estimation of glutamine and glutathione, and may help in the study of disturbed amygdala metabolism in pathologies such as anxiety disorder, autism and major depression.     

High‐resolution creatine mapping of mouse brain at 11.7 T using non‐steady‐state chemical exchange saturation transfer

The current study aims to optimize the acquisition scheme for the creatine chemical exchange saturation transfer weighted (CrCESTw) signal on mouse brain at 11.7 T, in which a strong magnetization transfer contrast (MTC) is present, and to further develop the polynomial and Lorentzian line‐shape fitting (PLOF) method for quantifying CrCESTw signal with a non‐steady‐state (NSS) acquisition scheme. Studies on a Cr phantom with cross‐linked bovine serum albumin (BSA) as well as on mouse brain demonstrated that the maximum CrCESTw signal was reached with a short saturation time determined by the rotating frame relaxation time of the MTC pool instead of the steady‐state saturation. The saturation power for the maximal signal was around 1–1.5 μT for Cr with 20% cross‐linked BSA and in vivo applications, but 2 μT was found to be most practical for signal stability. For the CrCEST acquisition with strong MTC interference, the optimal saturation power and length are completely different from those on Cr solution alone. This observation could be explained well using R_1ρ theory by incorporating the strong MTC pool. Finally, a high‐resolution Cr map was obtained on mouse brain using the PLOF method with the NSS CEST acquisition and a cryogenic coil. The Cr map obtained by CEST showed homogenous intensity across the mouse brain except for regions with cerebrospinal fluid.     

Difference spectroscopy using PRESS asymmetry: application to glutamate,glutamine, and myo‐inositol

A simple, clinically viable technique utilizing PRESS and strong coupling properties is presented for discrimination of coupled brain metabolites. The method relies on signal variation due to alteration of inter‐echo timings (PRESS asymmetry) while maintaining a constant total echo time. Spin response of singlets and weakly coupled spins is unchanged due to PRESS asymmetry, allowing difference spectroscopy to detect unobstructed strongly coupled resonances. No changes to the standard PRESS sequence are required except variation of inter‐echo timings. The procedure is illustrated for the separate detection of glutamate from glutamine and the detection of myo‐inositol in simulation, phantom, and in vivo experiments at 4.7 T. The subtraction yields calculated from the simulation were 53% for glutamate and 75% for myo‐inositol, and a resultant contribution of 96% glutamate to the total glutamate/glutamine multiplet in the 2.04–2.14 ppm range. To extend the treatment to other field strengths and metabolites, an analytical approximation based on a strongly coupled AB system was used to model individual spin groups. Subtraction spectroscopy yields for different combinations of coupling parameters were calculated for the detection of various strongly coupled metabolites at common clinical field strengths. The approximation also predicts adequate glutamate/glutamine discrimination at 3.0 T using the difference spectroscopy method. Copyright © 2009 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.     

Short TE single‐voxel 1H‐MR spectroscopy of hippocampal structures in healthy adults at 1.5 Tesla—how reproducible are the results?

The purpose of our study was to evaluate inter- and intra-subject variability and scan-rescan reproducibility of single-voxel 1H-MR spectroscopy (1H-MRS) in hippocampal structures at 1.5 T field strength. Thirty healthy adults were studied bilaterally by optimized, standardized short echo time single-voxel 1H-MRS (PRESS, TE=30 ms, TR=3000 ms, oblique voxel orientation, voxel size 2 cm3). Spectral analysis and absolute metabolite quantitation of N-acetylaspartate+N-acetylaspartyl-glutamate (tNAA), choline (Cho), creatine (Cr), total glutamate plus glutamine (Glu+Gln) and myo-inositol (Ins) were carried out by LCModel. Inter- and intra-individual reproducibility of these metabolite values were investigated by calculation of mean, standard deviation, coefficient of variation (CV), and by analysis of variance for repeated measurements. The smallest CV in intersubject variability was obtained for tNAA, followed by Cr, Cho, Ins and Glu+Gln. The results of the analysis of variance for repeated measures in inter-subject variability showed a marginal effect of scan repetition for Cr (p=0.063) and Glu+Gln (p=0.082); the rescan of both metabolites showed slightly higher concentrations. No statistical significant effect of scan repetition was seen for tNAA (p=0.913), Cho (p=0.857), and Ins (p=0.826). Rescan led to the same results and gave proof of good reproducibility. Scan-rescan testing in one subject showed comparable results: tNAA (CV=4.8%), followed by Cr, Ins, Glu+Gln and Cho (all CV above 10%).     

Mapping glutamate in subcortical brain structures using high‐resolution GluCEST MRI

In vivo measurement of glutamate (Glu) in brain subcortex can elucidate the role these structures play in cognition and neuropsychiatric disorders. However, accurate quantification of Glu in subcortical regions is challenging. Recently, a novel MRI method based on the Glu chemical exchange saturation transfer (GluCEST) effect has been developed for detecting brain Glu in millimolar concentrations. Here, we use GluCEST to map Glu distributions in subcortical structures of the human brain (e.g. amygdala, hippocampus). Overall, GluCEST was ~40% higher in gray matter than in white matter. Within the subcortical gray matters, amygdala showed the highest GluCEST contrast. Utilizing MR spectroscopic data, in vivo GluCEST detection sensitivity (~0.8% mM^?1) in subcortical gray matter was evaluated and was consistent with the previously reported values. In general, the GluCEST map approximates the Glu receptor distribution reported in previous positron emission tomography (PET) studies. These findings suggest that high‐resolution GluCEST MRI of subcortical brain structures may prove to be a useful tool in diagnosis of brain disorders or treatment responses. Copyright © 2013 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.     

Spectral fitting using basis set modified by measured B0 field distribution

This study sought to demonstrate and evaluate a novel spectral fitting method to improve quantification accuracy in the presence of large magnetic field distortion, especially with high fields. MRS experiments were performed using a point‐resolved spectroscopy (PRESS)‐type sequence at 7 T. A double‐echo gradient echo (GRE) sequence was used to acquire B₀ maps following MRS experiments. The basis set was modified based on the measured B₀ distribution within the MRS voxel. Quantification results were obtained after fitting the measured MRS data using the modified basis set. The proposed method was validated using numerical Monte Carlo simulations, phantom measurements, and comparison of occipital lobe MRS measurements under homogeneous and inhomogeneous magnetic field conditions. In vivo results acquired from voxels placed in thalamus and prefrontal cortex regions close to the frontal sinus agreed well with published values. Instead of noise‐amplifying complex division, the proposed method treats field variations as part of the signal model, thereby avoiding inherent statistical bias associated with regularization. Simulations and experiments showed that the proposed approach reliably quantified results in the presence of relatively large magnetic field distortion. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.     

Calculation methods for ventricular diffusion-weighted imaging thermometry: phantom and volunteer studies

A method for the measurement of temperature in the lateral ventricle using diffusion‐weighted imaging (DWI) has been proposed recently. This method uses predetermined arbitrary thresholds, but a more objective method of calculation would be useful. We therefore compared four different calculation methods, two of which were newly created and did not require predetermined thresholds. A rectangular polyethylene terephthalate bottle (8 × 10 × 28 cm³) was filled with heated water (35.0–38.8 °C) and used as a water phantom. The DWI data of 23 healthy subjects (aged 26–75 years; mean ± standard deviation, 50.13 ± 19.1 years) were used for this study. The temperature was calculated using the following equation: T(°C) = 2256.74/ln(4.39221/D) ? 273.15, where D is the diffusion coefficient. The mean ventricular temperature was calculated by four methods: two thresholding methods and two histogram curve‐fitting methods. As a reference, we used the temperature measured at the tympanic membrane, which is known to be approximately 1 °C lower than the brain temperature. The averaged differences in temperature between mercury thermometry and classical predetermined thresholding methods for the water phantom were 0.10 ± 0.42 and 0.05 ± 0.41 °C, respectively. The histogram curve‐fitting methods, however, yielded temperatures a little lower (averaged differences of ?0.24 ± 0.32 and ?0.14 ± 0.31 °C, respectively) than mercury thermometry. There was very little difference in temperature between tympanic thermometry and classical predetermined thresholding methods (+0.01 and ?0.07 °C, respectively). In humans, however, the histogram curve‐fitting methods yielded temperatures approximately 1 °C higher (+1.04 °C and +1.36 °C, respectively), suggesting that temperatures measured in this way more closely approximate the true brain temperature. The histogram curve‐fitting methods were more objective and better matched the estimated brain temperature than did classical predetermined thresholding methods, although the standard deviation was wider in the former methods. Copyright © 2011 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.     

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

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