James B. Murdoch

Carnosine, an MR‐visible dipeptide in human muscle, is well characterized by two peaks at ~8 and ~7 ppm from C2 and C4 imidazole protons. Like creatine and other metabolites, carnosine is subject to residual dipolar coupling in the anisotropic environment of muscle fibers, but the effects have not been studied extensively. Single‐voxel TE 30–32 PRESS spectra from three different 3T studies were acquired from gastrocnemius medialis and soleus muscles in the human lower leg. In these studies, carnosine T₂ values were measured, and spectra were obtained at three different foot angles. LCModel was used to fit the carnosine peaks with a basis set that was generated using shaped RF pulses and included a range of dipolar couplings affecting the C4 peak. A seven‐parameter analytic expression was used to fit the CH₂ doublets of creatine. It incorporated an optimized “effective TE” value to model the effect of shaped RF pulses. The fits confirm that the triplet C4 peak of carnosine is dipolar coupled to a pair of CH₂ protons, with no need to include a contribution from a separate pool of freely rotating uncoupled carnosine. Moreover, the couplings experienced by carnosine C4 protons and creatine CH₂ protons are strongly correlated (R² = 0.88, P2θ − 1 dependence on the angle θ between fiber orientation and B0. T₂ values for the singlet C2 peak of gastrocnemius carnosine are inversely proportional to the C4 dipolar coupling strength (R² = 0.97, P < 0.001), which in turn is a function of foot orientation. This dependence indicates that careful positioning of the foot while acquiring lower leg muscle spectra is important to obtain reproducible carnosine concentrations. As proton magnetic resonance spectroscopy of carnosine is currently used to non‐invasively estimate the muscle fiber typology, these results have important implications in sport science.

Edited MRS sequences are widely used for studying γ‐aminobutyric acid (GABA) in the human brain. Several algorithms are available for modelling these data, deriving metabolite concentration estimates through peak fitting or a linear combination of basis spectra. The present study compares seven such algorithms, using data obtained in a large multisite study. GABA‐edited (GABA+, TE = 68 ms MEGA‐PRESS) data from 222 subjects at 20 sites were processed via a standardised pipeline, before modelling with FSL‐MRS, Gannet, AMARES, QUEST, LCModel, Osprey and Tarquin, using standardised vendor‐specific basis sets (for GE, Philips and Siemens) where appropriate. After referencing metabolite estimates (to water or creatine), systematic differences in scale were observed between datasets acquired on different vendors' hardware, presenting across algorithms. Scale differences across algorithms were also observed. Using the correlation between metabolite estimates and voxel tissue fraction as a benchmark, most algorithms were found to be similarly effective in detecting differences in GABA+. An interclass correlation across all algorithms showed single‐rater consistency for GABA+ estimates of around 0.38, indicating moderate agreement. Upon inclusion of a basis set component explicitly modelling the macromolecule signal underlying the observed 3.0 ppm GABA peaks, single‐rater consistency improved to 0.44. Correlation between discrete pairs of algorithms varied, and was concerningly weak in some cases. Our findings highlight the need for consensus on appropriate modelling parameters across different algorithms, and for detailed reporting of the parameters adopted in individual studies to ensure reproducibility and meaningful comparison of outcomes between different studies.

Purpose: To evaluate the reproducibility of γ‐amino‐butyric acid (GABA) and glutamate concentrations derived using three different spectral fitting methods, and to investigate gender‐related differences in neurotransmitter levels.Materials and Methods: Single voxel MEGA‐edited PRESS MR spectra were acquired from a 30‐mL voxel in the dorso‐lateral prefrontal cortex in 14 adult volunteers (7 female) at 3 Tesla (3T). For each participant, four consecutive resting spectra were acquired within the same scanning session. Metabolite concentrations were derived using LCModel, jMRUI, and locally written peak fitting software. The within‐session reproducibility for each analysis method was calculated as the average coefficient of variation (CV) of the GABA and Glx (glutamate+glutamine) concentrations. Gender differences in GABA and Glx were evaluated using a two‐tailed unpaired t‐test.Results: LCModel provided the best reproducibility for both GABA (CV 7%) and Glx (CV 6%). GABA, Glx, and glutamate concentrations were significantly higher in the male participants, (P = 0.02, P = 0.001, and P < 0.001, respectively).Conclusion: GABA and glutamate can be quantified in vivo with high reproducibility (CV 6–7%) using frequency‐domain spectral fitting methods like LCModel. However, the GABA and glutamate concentrations vary significantly between men and women, emphasizing the importance of gender‐matching for studies investigating differences in neurotransmitter concentrations between mixed‐cohort groups. J. Magn. Reson. Imaging 2011;33:1262–1267.

BackgroundExposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable.ObjectivesOur goal was to determine whether in vivo brain levels of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure.MethodsWe used T1-weighted magnetic resonance imaging (MRI) to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate, and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. We used the MEGA-PRESS MRS sequence to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia [GABA-VOI (volume of interest)].ResultsSeven of 10 expo...

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.

Single‐voxel ¹H NMR spectra from gastrocnemius and soleus muscle were acquired in healthy volunteers at 7T with the objective of measuring the concentration of intramyocellular lipid [IMCL] (note: throughout this article, square brackets indicate concentration). However, significant asymmetry in the resonance assigned to the methylene protons (‐CH₂‐)_n in extramyocellular lipids (EMCL) interfered with fitting the spectra. Since muscle fibers in these tissues are generally not parallel to B₀, the influence of variable orientation in strands of extracellular fat was examined using a mathematical model. Modest variation in orientation produced asymmetric lineshapes that were qualitatively similar to typical observations at 7T. Analysis of simulated spectra by fitting with a Voigt function overestimated [IMCL]/[EMCL] except when EMCL fibers were nearly parallel to B₀. Estimates of [IMCL]/[EMCL] were improved by including variations in fiber orientation in the lineshape analysis (fiber orientation modeling, or FOM). Calculated [IMCL] using FOM, 4.8 ± 2.2 mmol/kg wet weight, was lower compared to most previous reports in soleus. Magn Reson Med 61:16–21, 2009.

Summary: A 69-year-old woman presented with clinical and imaging findings suspicious for gliomatosis cerebri, later confirmed by biopsy (moderately cellular, infiltrating glioma). Single voxel proton MR spectroscopy (TE 20 and TE 135) and spectroscopic imaging (TE 135) performed at admission showed normal choline, decreased N-acetyl, and elevated myo-inositol levels relative to creatine. The primary conclusion is that in suspected cases of gliomatosis cerebri, myo-inositol/creatine and myo-inositol/N-acetyl should be determined because they may provide evidence of tumor, even though choline/creatine is normal. A corollary to this conclusion is that choline/creatine may be misleading if used to demarcate infiltrating glioma from edema.

Summary: Proton MR spectroscopy is a powerful noninvasive method that enables measurement of certain brain metabolites in healthy subjects and patients with diseases. A major difficulty with clinical and research applications of in vivo proton MR spectroscopy is the variability of metabolite concentrations, especially in regions with substantial physiologic motion. In our preliminary evaluation, we tested the hypothesis that physiologic brain motion leads to lower mean metabolite concentrations and higher SDs for the measured metabolite concentrations.