Brain metabolites B1‐corrected proton T1 mapping in the rhesus macaque at 3 T

The accuracy of metabolic quantification in MR spectroscopy is limited by the unknown radiofrequency field and T₁. To address both issues in proton (¹H) MR spectroscopy, we obtained radiofrequency field–corrected T₁ maps of N‐acetylaspartate, choline, and creatine in five healthy rhesus macaques at 3 T. For efficient use of the 4 hour experiment, we used a new three‐point protocol that optimizes the precision of T₁ in three‐dimensional ¹H‐MR spectroscopy localization for extensive, ～30%, brain coverage at 0.6 × 0.6 × 0.5 cm³ = 180‐μL spatial resolution. The resulting mean T₁s in 700 voxels were N‐acetylaspartate = 1232 ± 44, creatine = 1238 ± 23 and choline = 1107 ± 56 ms (mean ± standard error of the mean). Their histograms from all 140 voxels in each animal were similar in position and shape, characterized by standard errors of the mean of the full width at half maximum divided by their means of better than 8%. Regional gray matter N‐acetylaspartate, choline, and creatine T₁s (1333 ± 43, 1265 ± 52, and 1131 ± 28 ms) were 5–10% longer than white matter: 1188 ± 34, 1201 ± 24, and 1082 ± 50 ms (statistically significant for the N‐acetylaspartate only), all within 10% of the corresponding published values in the human brain. Magn Reson Med 63:865–871, 2010. © 2010 Wiley‐Liss, Inc.     

Proton T1 relaxation times of metabolites in human occipital white and gray matter at 7 T

Proton T₁ relaxation times of metabolites in the human brain have not previously been published at 7 T. In this study, T₁ values of CH₃ and CH₂ group of N‐acetylaspartate and total creatine as well as nine other brain metabolites were measured in occipital white matter and gray matter at 7 T using an inversion‐recovery technique combined with a newly implemented semi‐adiabatic spin‐echo full‐intensity acquired localized spectroscopy sequence (echo time = 12 ms). The mean T₁ values of metabolites in occipital white matter and gray matter ranged from 0.9 to 2.2 s. Among them, the T₁ of glutathione, scyllo‐inositol, taurine, phosphorylethanolamine, and N‐acetylaspartylglutamate were determined for the first time in the human brain. Significant differences in T₁ between white matter and gray matter were found for water (?28%), total choline (?14%), N‐acetylaspartylglutamate (?29%), N‐acetylaspartate (+4%), and glutamate (+8%). An increasing trend in T₁ was observed when compared with previously reported values of N‐acetylaspartate (CH₃), total creatine (CH₃), and total choline at 3 T. However, for N‐acetylaspartate (CH₃), total creatine, and total choline, no substantial differences compared to previously reported values at 9.4 T were discernible. The T₁ values reported here will be useful for the quantification of metabolites and signal‐to‐noise optimization in human brain at 7 T. Magn Reson Med 69:931–936, 2013. © 2012 Wiley Periodicals, Inc.     

Simultaneous quantification of T2 and T′2 using a combined gradient echo‐spin echo sequence at ultrahigh field

Measuring T₂ at 7.0 T is not trivial due to RF inhomogeneity effects, however, gradient echo sampling of a spin echo is insensitive to RF pulse errors, does not suffer from significant distortions, and allows T′₂ and T₂ to be estimated simultaneously. Gradient echo sampling of a spin echo results are relatively sensitive to noise and therefore fitting methods and timing parameters were optimized: a weighted linear fit reduced the errors in T₂ compared to a nonlinear fit, the optimum spin echo time was approximately equal to the expected T₂ and decreasing the number of gradient echoes minimized the error of the estimated T₂. T₂, T′₂, and T*₂ decreased with field strength in frontal gray matter, occipital gray matter, and white matter, with T₂ having a linear dependence (frontal gray matter: 87, 76, 47 ms, occipital gray matter: 80, 68, 46 ms and white matter: 80, 71, 47 ms at 1.5, 3.0 and 7.0 T, respectively). Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Quantitative 1H spectroscopic imaging of human brain at 4.1 T using image segmentation

Metabolic differences in the content of N-acetylaspartate (NAA), creatine (CR), and choline (CH) in cerebral gray and white matter can complicate the interpretation of ¹H spectroscopic images. To account for these variations, the gray-and white-matter content of each voxel must be known. To provide these data, a T₁-based image segmentation scheme was implemented at 4.1 T. The tissue composition of each voxel was determined using the point-spread function of the spectroscopic imaging acquisition and the segmented anatomical image. Pure gray- and white-matter values for CR/NAA and CH/NAA, and the content of CR, CH, and NAA, were determined using a linear-regression analysis of 984 voxels acquired from 10 subjects using white-matter CR as an internal standard. This information was used to establish means and confidence intervals for CR/NAA and CH/NAA from a voxel of arbitrary tissue composition. Using a single-tailed t test, the extent and locations of the metabolic abnormalities (P < 0.05) in a patient with multiple sclerosis were identified.     

Regional metabolite T2 in the healthy rhesus macaque brain at 7T

Although the rhesus macaque brain is an excellent model system for the study of neurological diseases and their responses to treatment, its small size requires much higher spatial resolution, motivating use of ultra‐high‐field (B₀) imagers. Their weaker radio‐frequency fields, however, dictate longer pulses; hence longer TE localization sequences. Due to the shorter transverse relaxation time (T₂) at higher B₀s, these longer TEs subject metabolites to T₂‐weighting, that decrease their quantification accuracy. To address this we measured the T₂s of N‐acetylaspartate (NAA), choline (Cho), and creatine (Cr) in several gray matter (GM) and white matter (WM) regions of four healthy rhesus macaques at 7T using three‐dimensional (3D) proton MR spectroscopic imaging at (0.4 cm)³ = 64 μl spatial resolution. The results show that macaque T₂s are in good agreement with those reported in humans at 7T: 169 ± 2.3 ms for NAA (mean ± SEM), 114 ± 1.9 ms for Cr, and 128 ± 2.4 ms for Cho, with no significant differences between GM and WM. The T₂ histograms from 320 voxels in each animal for NAA, Cr, and Cho were similar in position and shape, indicating that they are potentially characteristic of “healthy” in this species. Magn Reson Med 59:1165–1169, 2008. © 2008 Wiley‐Liss, Inc.     

Metabolite proton T2 mapping in the healthy rhesus macaque brain at 3 T

The structure and metabolism of the rhesus macaque brain, an advanced model for neurologic diseases and their treatment response, is often studied noninvasively with MRI and ¹H‐MR spectroscopy. Due to the shorter transverse relaxation time (T₂) at the higher magnetic fields these studies favor, the echo times used in ¹H‐MR spectroscopy subject the metabolites to unknown T₂ weighting, decreasing the accuracy of quantification which is key for inter‐ and intra‐animal comparisons. To establish the “baseline” (healthy animal) T₂ values, we mapped them for the three main metabolites' T₂s at 3 T in four healthy rhesus macaques and tested the hypotheses that their mean values are similar (i) among animals; and (ii) to analogs regions in the human brain. This was done with three‐dimensional multivoxel ¹H‐MR spectroscopy at (0.6 × 0.6 × 0.5 cm)³ = 180 μL spatial resolution over a 4.2 × 3.0 × 2.0 = 25 cm³ (～30%) of the macaque brain in a two‐point protocol that optimizes T₂ precision per unit time. The estimated T₂s in several gray and white matter regions are all within 10% of those reported in the human brain (mean ± standard error of the mean): N‐acetylaspartate = 316 ± 7, creatine = 177 ± 3, and choline = 264 ± 9 ms, with no statistically significant gray versus white matter differences. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Differentiation of metabolic concentrations between gray matter and white matter of human brain by in vivo 1H magnetic resonance spectroscopy

Differentiation of absolute metabolite concentrations between gray and white matter in the occipital region of normal human brain was performed by in vivo localized single-voxel ¹H magnetic resonance spectroscopy at 1.5 Testa with long echo time (136 ms). With the combination of image segmentation between white and gray matter and cerebrospinal fluid, signal compensation of T, and T₂ effects, tissue water signal as the internal concentration reference, as well as compensation by different water contents in gray and white matters, it was determined that the levels of N-acetylaspartate (NAA), creatine and/or phosphocreatine (Cr), and choline-containing compounds (Cho) in gray matter were significantly higher than in white matter. The averaged NAA, Cr, and Cho concentrations in gray matter were 11.0, 9.7, and 1.9 mM/liter, respectively, in comparison with 7.5, 5.2, and 1.6 mM/liter in white matter. These results suggest that precise composition of white and gray matter and cerebrospinal fluid is necessary to avoid partial voluming effect in a single voxel and to accurately quantify the metabolite concentrations.     

Age dependence of regional proton metabolites T2 relaxation times in the human brain at 3 T

Although recent studies indicate that use of a single global transverse relaxation time, T₂, per metabolite is sufficient for better than ±10% quantification precision at intermediate and short echo‐time spectroscopy in young adults, the age‐dependence of this finding is unknown. Consequently, the age effect on regional brain choline (Cho), creatine (Cr), and N‐acetylaspartate (NAA) T₂s was examined in four age groups using 3D (four slices, 80 voxels 1 cm³ each) proton MR spectroscopy in an optimized two‐point protocol. Metabolite T₂s were estimated in each voxel and in 10 gray and white matter (GM, WM) structures in 20 healthy subjects: four adolescents (13 ± 1 years old), eight young adults (26 ± 1); two middle‐aged (51 ± 6), and six elderly (74 ± 3). The results reveal that T₂s in GM (average ± standard error of the mean) of adolescents (NAA: 301 ± 30, Cr: 162 ± 7, Cho: 263 ± 7 ms), young adults (NAA: 269 ± 7, Cr: 156 ± 7, Cho: 226 ± 9 ms), and elderly (NAA: 259 ± 13, Cr: 154 ± 8, Cho: 229 ± 14 ms), were 30%, 16%, and 10% shorter than in WM, yielding mean global T₂s of NAA: 343, Cr: 172, and Cho: 248 ms. The elderly NAA, Cr, and Cho T₂s were 12%, 6%, and 10% shorter than the adolescents, a change of under 1 ms/year assuming a linear decline with age. Formulae for T₂ age‐correction for higher quantification precision are provided. Magn Reson Med 60:790–795, 2008. © 2008 Wiley‐Liss, Inc.     

Contrast at high field: Relaxation times,magnetization transfer and phase in the rat brain at 16.4 T

As field strength increases, the magnetic resonance imaging contrast parameters like relaxation times, magnetization transfer or image phase change, causing variations in contrast and signal‐to‐noise ratio. To obtain reliable data for these parameters at 16.4 T, high‐resolution measurements of the relaxation times T₁, T₂ and T₂*, as well as of the magnetization transfer ratio and the local frequency in the rat brain were performed. Tissue‐specific values were obtained for up to 17 brain structures to assess image contrast. The measured parameters were compared to those found at different field strengths to estimate contrast and signal behavior at increasing field. T₁ values were relatively long with (2272 ± 113) ms in cortex and (2073 ± 97) ms in white matter, but did not show a tendency to converge, leading to an almost linear increase in signal‐to‐noise ratio and still growing contrast‐to‐noise ratio. T₂ was short with (25 ± 2) ms in cortex and (20 ± 1) ms in white matter. Magnetization transfer effects increase by around 25% compared to published 4.7 T data, which leads to improved contrast. The image phase, as novel and high‐field specific contrast mechanism, is shown to obtain good contrast in deep brain regions with increasing signal‐to‐noise ratio up to high field strengths. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Quantification of T2 in the abdomen at 3.0 T using a T2‐prepared balanced turbo field echo sequence

The T₂‐prepared balanced turbo field echo sequence has been used to measure T₂ in phantoms and in vivo in the abdomen with low sensitivity to radiofrequency pulse errors. The effects of noise, errors in the pulse flip angles, and off resonance effects on the results have been simulated. It was found from simulations that for normal conditions, including the flip angle in the fit improved the systematic errors due to radiofrequency pulse errors and noise in the results to less than 1% without significantly increasing the random errors. For a 0.3% noise level, the standard deviation in the measured T₂ was approximately 0.003 ms. Off‐resonance effects had a minimal effect on the measured T₂ value. The T₂ at 3.0 T of various abdominal organs was measured, in particular the liver (31 ± 6 ms), spleen (54 ± 15 ms), kidney cortex (76 ± 6 ms), kidney medulla (61 ± 8 ms), and pancreas (42 ± 20 ms). Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

In vivo measurement of T2 distributions and water contents in normal human brain

Using a 32-echo imaging pulse sequence, T₂ relaxation decay curves were acquired from five white- and six gray-matter brain structures outlined in 12 normal volunteers. The water contents of white and gray matter were 0.71 (0.01) and 0.83 (0.03) g/ml, respectively. All white-matter structures had significantly higher myelin water percentages (signal percentage with T₂ between 10 and 50 ms) than all gray-matter structures. The range in geometric mean T₂ of the main peak for both white and gray matter was from 70 to 86 ms. T₂ distributions from the posterior internal capsules and splenium of the corpus callosum were significantly wider (width is related to water environment inhomogeneity) than those from any other white- or gray-matter structures. Thus, quantitative measurement and analysis of T₂ relaxation reveals differences in brain tissue water environments not discernible on conventional MR images. These differences may make short T₂ components reliable markers for normal myelin.     

Measurement of transverse relaxation times of J‐coupled metabolites in the human visual cortex at 4 T

Accurate quantification of ¹H NMR spectra often requires knowledge of the relaxation times to correct for signal losses due to relaxation and saturation. In human brain, T₂ values for singlets such as N‐acetylaspartate, creatine, and choline have been reported, but few T₂ values are available for J‐coupled spin systems. The purpose of this study was to measure the T₂ relaxation times of J‐coupled metabolites in the human occipital lobe using the LASER sequence. Spectra were acquired at multiple echo times and were analyzed with an LCModel using basis sets simulated at each echo time. Separate basis spectra were used for resonances of protons belonging to the same molecule but having very different T₂ values (e.g., two separate basis spectra were used for the singlet and multiplet signal in N‐acetylaspartate). The T₂ values for the N‐acetylaspartate multiplet (149 ± 12 ms), glutamate (125 ± 10 ms), myo‐inositol (139 ± 20 ms), and taurine (196 ± 28 ms) were successfully measured in the human visual cortex at 4 T. These measured T₂ relaxation times have enabled the accurate and absolute quantification of cerebral metabolites at longer echo times. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Temporal and regional changes during focal ischemia in rat brain studied by proton spectroscopic imaging and quantitative diffusion NMR imaging

The early development of focal ischemia after permanent occlusion of the right middle cerebral artery (MCA) was studied in six rats using interleaved measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed between the control phase and approximately 6 h postocclusion. In the center of the ischemic lesion of all rats, the apparent diffusion coefficient (ADC) decreased rapidly to 84.4 ± 4.2% (mean ± SD) of the control values approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was reduced to 67.1 ± 5.9%. In contrast, large differences between the animals were observed for the temporal increase of lactate (Lac) in the ipsilateral hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI spectra measured at a TE of 136 ms revealed a decrease in the CH³ signal of N-acetylaspartate (NAA) to 67 ± 13% of the control values. Differences were observed between the spatial regions of decreased NAA and increased Lac. In the lesions, a T2 relaxation time of Lac of 292 ± 40 ms, considering a J-cou-pling constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T₂ of the CH₃ signal of creatine/phosphocre-atine (Cr/PCr) was observed in the lesion, from 163 ± 22 ms during control to 211 ± 41 ms approximately 6 h postocclusion. The experiments proved that DWI and proton SI are valuable tools to provide complementary information on processes associated with brain infarcts.     

Ultrashort TE T1ρ magic angle imaging

An ultrashort TE T₁ρ sequence was used to measure T₁ρ of the goat posterior cruciate ligament (n = 1) and human Achilles tendon specimens (n = 6) at a series of angles relative to the B₀ field and spin‐lock field strengths to investigate the contribution of dipole–dipole interaction to T₁ρ relaxation. Preliminary results showed a significant magic angle effect. T₁ρ of the posterior cruciate ligament increased from 6.9 ± 1.3 ms at 0° to 36 ± 5 ms at 55° and then gradually reduced to 12 ± 3 ms at 90°. Mean T₁ρ of the Achilles tendon increased from 5.5 ± 2.2 ms at 0° to 40 ± 5 ms at 55°. T₁ρ dispersion study showed a significant T₁ρ increase from 2.3 ± 0.9 ms to 11 ± 3 ms at 0° as the spin‐lock field strength increased from 150 Hz to 1 kHz, and from 30 ± 3 ms to 42 ± 4 ms at 55° as the spin‐lock field strength increased from 100 to 500 Hz. These results suggest that dipolar interaction is the dominant T₁ρ relaxation mechanism in tendons and ligaments. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Quantitative proton MR spectroscopic imaging of the human brain

Multislice proton MR spectroscopic images (SI) of the brain were quantitated, using the phantom replacement technique. In 16 normal volunteers, ranging in age from 5 to 74 years, average “whole brain” concentrations of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) were found to be 2.4 ± 0.4, 7.9 ± 1.3, and 11.8 ± 1.0 (mM, mean ± SD), respectively. These values are in good general agreement with those previously determined by single-voxel localization techniques. Cortical gray matter was found to have lower Cho and NAA levels, compared to those of white matter, corpus callosum, and basal ganglia. Cho was also found to increase significantly with age in several locations. Quantitative multislice proton SI is feasible in the clinical environment, and regional and age-dependent variations occur that must be accounted for when evaluating spectra from pathological conditions.     

Gray matter-white matter contrast on spin-echo T1-weighted images at 3 T and 1.5 T: a quantitative comparison study

Discrepancies exist in the literature regarding contrast between gray and white matter on spin-echo (SE) T1-weighted MR imaging at 3 T. The present study quantitatively assessed differences in gray matter-white matter contrast on both single- and multi-slice SE T1-weighted imaging between 3 and 1.5 T. SE T1-weighted sequences with the same parameters at both 3 and 1.5 T were used. Contrast-to-noise ratio (CNR) between gray and white matter (CNR_GM-WM) was evaluated for both frontal lobes. To assess the effects of interslice gap, multi-slice images were obtained with both 0 and 25% interslice gap. Single-slice CNR_GM-WM was higher at 3 T (17.66 ± 2.68) than at 1.5 T (13.09 ± 2.35; P < 0.001). No significant difference in CNR_GM-WM of multi-slice images with 0% gap was noted between 3 and 1.5 T (3T, 8.61 ± 2.55; 1.5T, 7.43 ± 1.20; P > 0.05). Multi-slice CNR_GM-WM with 25% gap was higher at 3T (12.47 ± 3.31) than at 1.5 T (9.73 ± 1.37; P < 0.001). CNR_GM-WM reduction rate of multi-slice images with 0% gap compared with single-slice images was higher at 3T (0.47 ± 0.13) than at 1.5 T (0.38 ± 0.09; P = 0.02). CNR_GM-WM on single-slice SE T1-weighted imaging and CNR_GM-WM on multi-slice images with 25% interslice gap were better at 3 T than at 1.5 T. The influence of multi-slice imaging on CNR_GM-WM was significantly larger at 3T than at 1.5 T. This study was supported in part by a Health and Labour Sciences Research Grant of Japan Yasutaka Fushimi and Yukio Miki equally contributed to the study.     

High‐resolution maps of magnetization transfer with inherent correction for RF inhomogeneity and T1 relaxation obtained from 3D FLASH MRI

An empirical equation for the magnetization transfer (MT) FLASH signal is derived by analogy to dual‐excitation FLASH, introducing a novel semiquantitative parameter for MT, the percentage saturation imposed by one MT pulse during TR. This parameter is obtained by a linear transformation of the inverse signal, using two reference experiments of proton density and T₁ weighting. The influence of sequence parameters on the MT saturation was studied. An 8.5‐min protocol for brain imaging at 3 T was based on nonselective sagittal 3D‐FLASH at 1.25 mm isotropic resolution using partial acquisition techniques (TR/TE/α = 25ms/4.9ms/5° or 11ms/4.9ms/15° for the T₁ reference). A 12.8 ms Gaussian MT pulse was applied 2.2 kHz off‐resonance with 540° flip angle. The MT saturation maps showed an excellent contrast in the brain due to clearly separated distributions for white and gray matter and cerebrospinal fluid. Within the limits of the approximation (excitation <15°, TR/T₁ ? 1) the MT term depends mainly on TR, the energy and offset of the MT pulse, but hardly on excitation and T₁ relaxation. It is inherently compensated for inhomogeneities of receive and transmit RF fields. The MT saturation appeared to be a sensitive parameter to depict MS lesions and alterations of normal‐appearing white matter. Magn Reson Med 60:1396–1407, 2008. © 2008 Wiley‐Liss, Inc.     

MR angiography of the cerebral perforating arteries with magnetization prepared anatomical reference at 7T: Comparison with time‐of‐flight

Purpose

To develop a magnetic resonance imaging (MRI) protocol that visualizes both the perforating arteries and the related anatomy in a single acquisition at 7T.

Material and Methods

T₁‐weighted magnetization prepared imaging (MPRAGE) was empirically modified for use as angiography method at 7T. The resulting sequence depicts the vasculature simultaneously with the surrounding anatomical structures, and is referred to as “magnetization prepared anatomical reference MRA” (MPARE‐MRA). The method was compared to time‐of‐flight (TOF) MRA in seven healthy subjects. The conspicuity of the perforating arteries and the contrast between gray and white matter were evaluated both quantitatively by contrast‐to‐noise (CNR) measurements, and qualitatively by two radiologists who scored the images.

Results

The contrast‐to‐noise ratio (CNR) between blood and background was 28 ± 9 for MPARE‐MRA and 35 ± 16 for TOF‐MRA, indicating good conspicuity of the vessels. CNR values were: internal capsule (IC) vs. caudate head (CH): 4.2 ± 0.7; IC vs. putamen: 3.5 ± 0.6; white matter vs. gray matter: 9.7 ± 2.5.

Conclusion

The benefits of ultra‐high‐field MRI can transform MPRAGE into a new angiography method to image small vessels and associated parenchyma at the same time. This technique can be used to study the correlation between tissue damage and vascular pathology. J. Magn. Reson. Imaging 2008;28:1519–1526. © 2008 Wiley‐Liss, Inc.     

Evaluation of multiple sclerosis by 1H spectroscopic imaging at 4.1 T

The authors report on high-field (4.1 T) magnetic resonance ¹H spectroscopic imaging studies on eight patients with relapsing remitting multiple sclerosis (mean expanded disability status scale (EDSS) 1.0) and eight normal controls. Using T₁ weighted imaging to determine lesion position, the authors found the ratios of choline/N-acetyl (NA) compounds and creatine/NA were increased significantly in the multiple sclerosis (MS) patients relative to controls in lesioned tissue, adjacent to lesion, far removed from lesions as well as in periventricular tissue. The gray matter creatine/NA was mildly increased (P < 0.01) in the MS patients, whereas the elevated gray-matter ratio of choline/NA was of borderline significance (P = 0.13). A more detailed comparison of white-matter and mean graymatter metabolite values indicates that creatine is increased greatest in areas far from lesions. This is in contrast to choline, which was greatest in lesions, and NA, which was smallest in lesions. It is postulated that the creatine increase may reflect an astrocytic (gliotic) or oligodendrocytic remyelinating process. The increased choline most likely reflects varying levels of inflammation and membrane turnover, whereas the NA decrease is representative of axonal dysfunction or loss.     

Measurement of glycine in gray and white matter in the human brain in vivo by 1H MRS at 7.0 T

The concentration of glycine (Gly) was measured in gray matter (GM) and white matter (WM) in the human brain using single‐voxel localized ¹H MRS at 7 T. A point‐resolved spectroscopy sequence with echo time = 150 ms was used for measuring Gly levels in various regions of the frontal and occipital lobes in 11 healthy volunteers and one subject with a glioblastoma. The point‐resolved spectroscopy spectra were analyzed with LCModel using basis functions generated from density matrix simulations that included the effects of volume localized radio‐frequency and gradient pulses. The fraction of GM and white matter within the voxels was obtained from T₁‐weighted image segmentation. The metabolite concentrations within the voxels, estimated with respect to the GM + WM water concentrations, were fitted to a linear function of fractional GM content. The Gly concentrations in pure GM and white matter were estimated to be 1.1 and 0.1 mM, with 95% confidence intervals 1.0–1.2 and 0.0–0.2, respectively. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.