Repeatability of 31P MRSI in the human brain at 7 T with and without the nuclear Overhauser effect

An often‐employed strategy to enhance signals in ³¹P MRS is the generation of the nuclear Overhauser effect (NOE) by saturation of the water resonance. However, NOE allegedly increases the variability of the ³¹P data, because variation is reported in NOE enhancements. This would negate the signal‐to‐noise (SNR) gain it generates. We hypothesized that the variation in NOE enhancement values is not caused by the variability in NOE itself, but is attributable to measurement uncertainties in the values used to calculate the enhancement. If true, the expected increase in SNR with NOE would improve the repeatability of ³¹P MRS measurements. To verify this hypothesis, a repeatability study of native and NOE‐enhanced ³¹P MRSI was performed in the brains of seven healthy volunteers at 7 T. The repeatability coefficient (RC) and the coefficient of variation in repeated measurements (CoV_repeat) were determined for each method, and the 95% limits of agreement (LoAs) between native and NOE‐enhanced signals were calculated. The variation between the methods, defined by the LoA, is at least as great as that predicted by the RC of each method. The sources of variation in NOE enhancements were determined using variance component analysis. In the seven metabolites with a positive NOE enhancement (nine metabolite resonances assessed), CoV_repeat improved, on average, by 15%. The LoAs could be explained by the RCs of the individual methods for the majority of the metabolites, generally confirming our hypothesis. Variation in NOE enhancement was mainly attributable to the factor repeat, but between‐voxel effects were also present for phosphoethanolamine and (glycero)phosphocholine. CoV_repeat and fitting error were strongly correlated and improved with positive NOE. Our findings generally indicate that NOE enhances the signal of metabolites, improving the repeatability of metabolite measurements. Additional variability as a result of NOE was minimal. These findings encourage the use of NOE‐enhanced ³¹P MRSI. Copyright © 2015 John Wiley & Sons, Ltd.     

Reproducibility of 7-T brain spectroscopy using an ultrashort echo time STimulated Echo Acquisition Mode sequence and automated voxel repositioning

Establishing the reproducibility of brain MRS is important for clinical studies so that researchers can evaluate changes in metabolites due to treatment or the course of a disease and better understand the brain in healthy and disordered states. Prior 7-T MRS reproducibility studies using the stimulated echo acquisition mode (STEAM) sequence have focused on the anterior cingulate cortex or posterior cingulate cortex and precuneus. The purpose of this study was to evaluate the reproducibility of metabolite measurements in the dorsolateral prefrontal cortex (DLPFC) using an ultrashort echo time (TE) STEAM sequence and automated voxel repositioning. Spectra were acquired during two scan sessions from nine subjects using the AutoAlign method for voxel repositioning. Reproducibility was evaluated with coefficients of variation (CVs) and percentage differences. The mean intrasubject CVs were less than 6% for the major metabolites glutamate, N-acetylaspartate, total creatine, total choline, and myo-inositol. The mean CVs were less than 20% for the smaller signals of GABA, glutamine, glutathione, and taurine. These results indicate that 7-T MRS using a STEAM sequence with ultrashort TE and automated voxel repositioning provides excellent reproducibility of metabolites in the DLPFC.     

High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging

Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging.     

Phosphorus-31 MR spectroscopy of normal adult human brain and brain tumours

Localized phosphorus-31 MR spectra were obtained in vivo in a large series of normal human brain tissue specimens of healthy volunteers (n=36) and various brain tumours (n=52). Tumour types examined included grade II and grade III gliomas (n=15 and n=1, respectively), glioblastomas (n=16) and meningeomas (n=12). An additional eight tumours were analysed during chemo- or radiotherapy. Spectra were acquired using a modified ISIS pulse sequence with a repetition time of 3 s. Voxel sizes ranged from 56 to 129 ml. The spectra were evaluated using a least-square variable projection (VARPRO) fitting procedure in the time domain, which allows semi-quantitative determination of relative metabolite concentrations. The measurements in normal cerebrum of healthy volunteers revealed the following results of metabolite signal intensity ratios: pH 7.04 (+/- 0.01), PCr/alpha-ATP 0.51 (+/- 0.03), P(i)/alpha-ATP 0.17 (+/-0.02), PCr/P(i) 2.09 (+/-0.12), PDE/alpha-ATP 3.65 (+/-0.13) and PME/alpha-ATP 0.41 (+/-0.04). Meningiomas showed the most obvious changes when compared with normal brain tissue. They are characterized by an alkaline environment (pH 7.16 +/- 0.03; p<0.005), a decrease in the phosphocreatine peak (p<0.0001) and significantly decreased phosphodiesters (p<0.0001). Glioblastomas also showed alkalization (pH 7.12 +/- 0.02; p<0.001) and a decrease in PDE/alpha-NTP (p<0.05), but no significant changes in PCr/alpha-NTP or PCr/Pi. In gliomas with low malignancy, less distinct changes could be detected with slight alkalization (pH 7.09 +/- 0.02; p<0.05) and more than a two-fold reduction in the PDE/alpha-NTP ratio (p<0.05). The spectra of brain tumours during chemo- and radiotherapy indicated clear but inconsistent influence of the therapy.     

Characterization of the response of taurine protons to PRESS at 9.4 T for Resolving choline and Determining taurine T2

Point‐resolved spectroscopy (PRESS), characterized by two TEs (TE₁ and TE₂), can be employed to perform animal magnetic resonance spectroscopy (MRS) studies at 9.4 T. Taurine (Tau) and choline (Cho) are relevant metabolites that can be measured by MRS. In this work, the response of the J‐coupled protons of Tau as a function of PRESS TE₁ and TE₂ was characterized at 9.4 T to achieve two objectives. The first was to determine two TE₁ and TE₂ combinations that could be used to obtain T₂‐corrected measures of Tau (3.42 ppm) that were minimally influenced by J coupling. The second was to exploit the Tau J coupling to find a timing combination that minimized the 3.25‐ppm Tau signal to enable the Cho (3.22 ppm) resonance to be resolved from the overlapping Tau signal. The response of Tau protons was investigated both numerically and experimentally. It was numerically determined that the timings {TE₁, TE₂} = {17 ms, 10 ms} and {TE₁, TE₂} = {80 ms, 70 ms} yielded similar 3.42‐ppm Tau resonance areas (5% difference), rendering them suitable for Tau T₂ determination. {TE₁, TE₂} = {25 ms, 50 ms} was found to yield minimal 3.25‐ppm Tau signal, reducing its interference with Cho. The efficacy of the timings was demonstrated on phantom solutions and in vivo in four Sprague Dawley rats. LCModel was employed to analyse the in vivo spectra and Tau T₂ values were estimated by fitting the Tau peak areas obtained with {TE₁, TE₂} = {17 ms, 10 ms} and {TE₁, TE₂} = {80 ms, 70 ms} to a monoexponentially decaying function. An average Tau T₂ of 106 ms (standard deviation, 12 ms) was obtained. LCModel analysis of rat spectra obtained with {TE₁, TE₂} = {25 ms, 50 ms} demonstrated negligible levels of Tau signal, compared with that obtained with short TE.     

Homogeneous B1+ for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

To explore the use of five meandering dipole antennas in a multi‐transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B₁ field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B₁ map, a T₁‐weighted image, and a T₂‐weighted image were acquired to assess B₁ efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR_10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of ?11.8 dB, and a maximum inter‐element coupling of ?14.2 dB. The maximum coupling between the antennas and the receive loops was ?18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T₁‐weighted images with a high spatial resolution of 0.7 mm³ isotropic and T₂‐weighted spin echo images with uniformly weighted contrast.     

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.     

Reproducibility of whole‐brain temperature mapping and metabolite quantification using proton magnetic resonance spectroscopy

Assessing brain temperature can provide important information about disease processes (e.g., stroke, trauma) and therapeutic effects (e.g., cerebral hypothermia treatment). Whole‐brain magnetic resonance spectroscopic imaging (WB‐MRSI) is increasingly used to quantify brain metabolites across the entire brain. However, its feasibility and reliability for estimating brain temperature needs further validation. Therefore, the present study evaluates the reproducibility of WB‐MRSI for temperature mapping as well as metabolite quantification across the whole brain in healthy volunteers. Ten healthy adults were scanned on three occasions 1 week apart. Brain temperature, along with four commonly assessed brain metabolites—total N‐acetyl‐aspartate (tNAA), total creatine (tCr), total choline (tCho) and myo‐inositol (mI)—were measured from WB‐MRSI data. Reproducibility was evaluated using the coefficient of variation (CV). The measured mean (range) of the intra‐subject CVs was 0.9% (0.6%‐1.6%) for brain temperature mapping, and 4.7% (2.5%‐15.7%), 6.4% (2.4%‐18.9%) and 14.2% (4.4%‐52.6%) for tNAA, tCho and mI, respectively, with reference to tCr. Consistently larger variability was found when using H₂O as the reference for metabolite quantifications: 7.8% (3.3%‐17.8%), 7.8% (3.1%‐18.0%), 9.8% (3.7%‐31.0%) and 17.0% (5.9%‐54.0%) for tNAA, tCr, tCho and mI, respectively. Further, the larger the brain region (indicated by a greater number of voxels within that region), the better the reproducibility for both temperature and metabolite estimates. Our results demonstrate good reproducibility of whole‐brain temperature and metabolite measurements using the WB‐MRSI technique.     

Early detection of changes in phospholipid metabolism during neoadjuvant chemotherapy in breast cancer patients using phosphorus magnetic resonance spectroscopy at 7T

The purpose of this work was to investigate whether noninvasive early detection (after the first cycle) of response to neoadjuvant chemotherapy (NAC) in breast cancer patients was possible. ³¹P‐MRSI at 7 T was used to determine different phosphor metabolites ratios and correlate this to pathological response. ³¹P‐MRSI was performed in 12 breast cancer patients treated with NAC. ³¹P spectra were fitted and aligned to the frequency of phosphoethanolamine (PE). Metabolic signal ratios for phosphomonoesters/phosphodiesters (PME/PDE), phosphocholine/glycerophosphatidylcholine (PC/GPtC), phosphoethanolamine/glycerophosphoethanolamine (PE/GPE) and phosphomonoesters/in‐organic phosphate (PME/Pi) were determined from spectral fitting of the individual spectra and the summed spectra before and after the first cycle of NAC. Metabolic ratios were subsequently related to pathological response. Additionally, the correlation between the measured metabolic ratios and Ki‐67 levels was determined using linear regression. Four patients had a pathological complete response after treatment, five patients a partial pathological response, and three patients did not respond to NAC. In the summed spectrum after the first cycle of NAC, PME/Pi and PME/PDE decreased by 18 and 13%, respectively. A subtle difference among the different response groups was observed in PME/PDE, where the nonresponders showed an increase and the partial and complete responders a decrease (P = 0.32). No significant changes in metabolic ratios were found. However, a significant association between PE/Pi and the Ki‐67 index was found (P = 0.03). We demonstrated that it is possible to detect subtle changes in ³¹P metabolites with a 7 T MR system after the first cycle of NAC treatment in breast cancer patients. Nonresponders showed different changes in metabolic ratios compared with partial and complete responders, in particular for PME/PDE; however, more patients need to be included to investigate its clinical value.     

Noninvasive quantification of intracellular sodium in human brain using ultrahigh–field MRI

In vivo sodium magnetic resonance imaging (MRI) measures tissue sodium content in living human brain but current methods do not allow noninvasive quantitative assessment of intracellular sodium concentration (ISC) – the most useful marker of tissue viability. In this study, we report the first noninvasive quantitative in vivo measurement of ISC and intracellular sodium volume fraction (ISVF) in healthy human brain, made possible by measuring tissue sodium concentration (TSC) and intracellular sodium molar fraction (ISMF) at ultra‐high field MRI. The method uses single–quantum (SQ) and triple–quantum filtered (TQF) imaging at 7 Tesla to separate intra‐ and extracellular sodium signals and provide quantification of ISMF, ISC and ISVF. This novel method allows noninvasive quantitative measurement of ISC and ISVF, opening many possibilities for structural and functional metabolic studies in healthy and diseased brains. Copyright © 2012 John Wiley & Sons, Ltd.     

Eight‐channel transceiver RF coil array tailored for 1H/19F MR of the human knee and fluorinated drugs at 7.0 T

The purpose of this study was to evaluate the feasibility of an eight‐channel dual‐tuned transceiver surface RF coil array for combined ¹H/¹⁹F MR of the human knee at 7.0 T following application of ¹⁹F‐containing drugs. The ¹H/¹⁹F RF coil array includes a posterior module with two ¹H loop elements and two anterior modules, each consisting of one ¹H and two ¹⁹F elements. The decoupling of neighbor elements is achieved by a shared capacitor. Electromagnetic field simulations were performed to afford uniform transmission fields and to be in accordance with RF safety guidelines. Localized ¹⁹F MRS was conducted with 47 and 101 mmol/L of flufenamic acid (FA) – a ¹⁹F‐containing non‐steroidal anti‐inflammatory drug – to determine T₁ and T₂ and to study the ¹⁹F signal‐to‐dose relationship. The suitability of the proposed approach for ¹H/¹⁹F MR was examined in healthy subjects. Reflection coefficients of each channel were less than ?17 dB and coupling between channels was less than ?11 dB. Q_L/Q_U was less than 0.5 for all elements. MRS results demonstrated signal stability with 1% variation. T₁ and T₂ relaxation times changed with concentration of FA: T₁/T₂ = 673/31 ms at 101 mmol/L and T₁/T₂ = 616/26 ms at 47 mmol/L. A uniform signal and contrast across the patella could be observed in proton imaging. The sensitivity of the RF coil enabled localization of FA ointment administrated to the knee with an in‐plane spatial resolution of (1.5 × 1.5) mm² achieved in a total scan time of approximately three minutes, which is well suited for translational human studies. This study shows the feasibility of combined ¹H/¹⁹F MRI of the knee at 7.0 T and proposes T₁ and T₂ mapping methods for quantifying fluorinated drugs in vivo. Further technological developments are necessary to promote real‐time bioavailability studies and quantification of ¹⁹F‐containing medicinal compounds in vivo. Copyright © 2015 John Wiley & Sons, Ltd.     

Morphology and morphometry of the human early foetal brain: A three-dimensional analysis

Morphometric analyses in the early foetal phase (9-13 postconceptional week) are critical for evaluating normal brain growth. In this study, we assessed sequential morphological and morphometric changes in the foetal brain during this period using high-resolution T1-weighted magnetic resonance imaging (MRI) scans from 21 samples preserved at Kyoto University. MRI sectional views (coronal, mid-sagittal, and horizontal sections) and 3D reconstructions of the whole brain revealed sequential changes in its external morphology and internal structures. The cerebrum's gross external view, lateral ventricle and choroid plexus, cerebral wall, basal ganglia and thalamus, and corpus callosum were assessed. The development of the cerebral cortex, white matter microstructure, and basal ganglia can be well-characterized using MRI scans. The insula became apparent and deeply impressed as brain growth progressed. A thick, densely packed cellular ventricular/subventricular zone and ganglionic eminence became apparent at high signal intensity. We detected the emergence of important landmarks which may be candidates in the subdivision processes during the early foetal period; the corpus callosum was first detected in the sample with crown-rump length (CRL) 62 mm. A primary sulcus on the medial part of the cortex (cingulate sulcus) was observed in the sample with CRL 114 mm. In the cerebellum, the hemispheres, posterolateral fissure, union of the cerebellar halves, and definition of the vermis were observed in the sample with CRL 43.5 mm, alongside the appearance of a primary fissure in the sample with CRL 56 mm and the prepyramidal fissure in the sample with CRL 75 mm. The volumetric, linear, and angle measurements revealed the comprehensive and regional development, growth, and differentiation of brain structures during the early foetal phase. The early foetal period was neither morphologically nor morphometrically uniform. The cerebral proportion (length/height) and the angle of cerebrum to the standard line at the lateral view of the cerebrum, which may reflect the growth and C-shape formation of the cerebrum, may be a candidate for subdividing the early foetal period. Future precise analyses must establish a staging system for the brain during the early foetal period. This study provides insights into brain structure, allowing for a correlation with functional maturation and facilitating the early detection of brain damage and abnormal development.     

In vivo brain (31)P-MRS: measuring the phospholipid resonances at 4 Tesla from small voxels

An optimized phosphorous ((31)P) three-dimensional chemical-shift imaging (3D-CSI) protocol was developed at 4 T to study the phospholipid metabolism from discrete regions in the human brain without the need for (1)H-decoupling or nuclear Overhauser enhancement (NOE). In this study, a spherically bound, weighted average, random point omission 3D-CSI technique was developed and tested, based on methods proposed in the literature. The technique yields a significant (p < 0.001, two-tailed, 5% confidence level) increase in signal-to-noise (SNR) efficiency over conventional 3D-CSI (phantom 32%), without an increase in voxel bleedthrough. An automated time-domain fitting procedure utilizing prior spectral knowledge quantified the individual brain phospholipid metabolites from 15 cm(3) effective (8.0 cm(3) nominal) volumes from the left/right-parieto-occipital cortex and left/right thalamus in 10 normal volunteers. Individual constituents from the phosphomonoester (PME) region; phosphoethanolamine (PEth), phosphocholine (PCh) and the phosphodiester (PDE) region; glycerophosphoethanolamine (GPEth), glycerophosphocholine (GPCh) and membrane phospholipids (MP) were separately quantified to assess the precision of our method at 4 T against previous (1)H-decoupled (31)P-MRS brain studies at lower fields and much larger voxels. Derived concentrations (mM/l tissue) for PEth, PCh, GPEth, GPCh and MP in the left-parieto-occipital cortex were 0.81 +/- 0.21, 0.46 +/- 0.14, 0.74 +/- 0.30, 1.15 +/- 0.43 and 1.54 +/- 0.95 mM, respectively, and 0.94 +/- 0.16, 0.46 +/- 0.17, 0.83 +/- 0.22, 1.14 +/- 0.40 and 1.26 +/- 0.78 mM for the right parieto-occipital cortex. Derived concentrations (mM/l tissue) for PEth, PCh, GPEth, GPCh and MP in the left-thalamus were 0.69 +/- 0.18, 0.42 +/- 0.16, 0.63 +/- 0.20, 1.05 +/- 0.42 and 0.93 +/- 0.56 mM, respectively, and 0.68 +/- 0.24, 0.34 +/- 0.18, 0.60 +/- 0.23, 1.09 +/- 0.36 and 0.74 +/- 0.48 mM for the right-thalamus. This is the first study to our knowledge that has been able to quantify each of these individual phospholipid metabolites from such small voxels in the brain within a clinically reasonable scan time and without (1)H-decoupling or NOE.     

Reproducibility of brain MRS in older healthy adults at 7T

To date, the majority of MRS reproducibility studies have been conducted in healthy younger adults, with only a few conducted in older adults at 3 T. With the growing interest in applying MRS methods to study the longitudinal course and effects of treatments in neurodegenerative disease, it is important to establish reproducibility in age‐matched controls, especially in older individuals. In this study, spectroscopic data were acquired using a stimulated echo acquisition mode (STEAM) localization technique in two regions (anterior and posterior cingulate cortices—ACC, PCC, respectively) in 10 healthy, cognitively normal older adults (64 ± 8.1 years). Reproducibility was assessed via mean coefficients of variation (CVs) and relative differences (RDs) calculated across two visits performed 2–3 months apart. Metabolites with high signal‐to‐noise ratio (SNR) such as NAA, tCho, and Glu had mean CVs of 10% or less and mean RDs of 15% or less across both regions. Metabolites with lower SNR such as GABA and Gln had slightly higher mean CVs of 22% or less and mean RDs of 27% or less across both regions. These results demonstrate the feasibility of acquiring MRS data at 7 T in older subjects, and establish that the spectroscopic data are reproducible in both the ACC and PCC in older, healthy subjects to the same extent as in previous studies in young subjects.     

High resolution MRI evaluation of meniscal volume and anthropometric correlations

The purpose of this study was to digitally determine meniscal volumes, and compare them with linear and surface area anthropometric measurements to evaluate these measurements for meniscal allograft sizing. Eighteen subjects (10 male and 8 female; mean age 37.5 years) underwent 3.0 T knee magnetic resonance imaging (MRI) of the dominant leg. The following morphometric measurements were evaluated: medial meniscal volume (MMV), lateral meniscal volume (LMV), tibial plateau width (TPW), width of the femoral condyles (WFC), and tibial plateau surface area (TPSA). MMV and LMV were compared to TPW, WFC, and TPSA. Meniscal volume and TPW were correlated to height and body‐mass index (BMI) and stratified by gender. Statistical analysis included coefficient of determination (r²) between MRI‐based MMV, LMV, TPW, TPSA, WFC, height, BMI, and gender. Significance was set at the P = 0.05 level. The mean MMV was 2275 mm³ and the mean LMV was 2102 mm³. TPW correlated well with meniscal volumes (r² > 0.62). WFC and TPSA correlated with meniscal volumes in the range of 0.40 < r² < 0.61. Height, BMI, and gender correlated poorly with total meniscal volume and TPW with values of r² < 0.44. Medial and lateral menisci have statistically similar volumes. TPW had the greatest utility for volumetric meniscal sizing. MRI‐based TPW can be considered as a statistically accurate measurement for determining meniscal volumes and meniscal size. Clin. Anat. 28:786–791, 2015. © 2015 Wiley Periodicals, Inc.     

Role of the MHC restriction during maturation of antigen‐specific human T cells in the thymus

In the thymus, a T‐cell repertoire able to confer protection against infectious and noninfectious agents in a peptide‐dependent, self‐MHC‐restricted manner is selected. Direct detection of Ag‐specific thymocytes, and analysis of the impact of the expression of the MHC‐restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer‐based enrichment protocol to analyze the ex vivo frequency and activation‐phenotype of human thymocytes specific for self, viral and tumor‐antigens presented by HLA‐A*0201 (A2) in individuals expressing or not this allele. Ag‐specific thymocytes were quantified within both CD4CD8 double or single‐positive compartments in every donor. Our data indicate that the maturation efficiency of Ag‐specific thymocytes is poorly affected by HLA‐A2 expression, in terms of frequencies. Nevertheless, A2‐restricted T‐cell lines from A2⁺ donors reacted to A2⁺ cell lines in a highly peptide‐specific fashion, whereas their alloreactive counterparts showed off‐target activity. This first ex vivo analysis of human antigen‐specific thymocytes at different stages of human T‐cell development should open new perspectives in the understanding of the human thymic selection process.     

Age‐related changes in brain energetics and phospholipid metabolism

Evidence suggests that mitochondria undergo functional and morphological changes with age. This study aimed to investigate the relationship of brain energy metabolism to healthy aging by assessing tissue specific differences in metabolites observable by phosphorus (³¹P) MRS. ³¹P MRSI at 4 Tesla (T) was performed on 34 volunteers, aged 21–84, screened to exclude serious medical and psychiatric diagnoses. Linear mixed effects models were used to analyze the effects of age on phosphorus metabolite concentrations, intracellular magnesium and pH estimates in brain tissue. A significant age associated decrease in brain pH (?0.53% per decade), increase in PCr (1.1% per decade) and decrease in PME (1.7% per decade) were found in total tissue, with PCr effects localized to the gray matter. An increase in beta NTP as a function of age (1% per decade) approached significance (p = 0.052). There were no effects demonstrated with increasing age for intracellular magnesium, PDE or inorganic phosphate. This study reports the effects of healthy aging on brain chemistry in the gray matter versus white matter using ³¹P MRS measures of high energy phosphates, pH and membrane metabolism. Increased PCr, increased beta NTP (reflecting ATP) and reduced pH may reflect altered energy production with healthy aging. Unlike some previous studies of aging and brain chemistry, this study examined healthy, non‐demented and psychiatrically stable older adults and specifically analyzed gray‐white matter differences in brain metabolism. Copyright © 2009 John Wiley & Sons, Ltd.     

Altered brain activation during response inhibition in obstructive sleep apnea

This study examined response inhibition during a Go–NoGo task in individuals with obstructive sleep apnea (OSA). Fourteen OSA patients and 14 controls were studied with functional magnetic resonance imaging. Compared to controls, the OSA group showed more false positives (error of commission) during the NoGo trials with decreased brain activation in the left postcentral gyrus, cingulate gyrus and inferior parietal lobe, as well as right insula and putamen. This is consistent with previous findings of impaired performance and decreased brain activation in OSA patients during a working memory task, suggesting that compromised brain function in response to cognitive challenges may underlie some of the cognitive deficits seen in patients with OSA.     

Proton T2 relaxation time of J-coupled cerebral metabolites in rat brain at 9.4 T

Knowledge of proton T2 relaxation time of metabolites is essential for proper quantitation of metabolite concentrations in localized proton spectroscopy, especially at moderate to long TEs. Although the T2 relaxation time of singlets, such as that of creatine and N-acetylaspartate, has been characterized in several studies, similar information is lacking from coupled spin resonances of cerebral metabolites. In this study, the T2 relaxation time of coupled spin resonances and singlet resonances of cerebral metabolites was measured in rat brain in vivo at 9.4 T. Spectra were acquired at 11 TEs using the SPin ECho, full Intensity Acquired Localized (SPECIAL) spectroscopy method. Data analysis was performed in the frequency domain with the LCModel software using simulated TE-specific basis sets. The T2 relaxation times in compounds showing singlet resonances were 113 +/- 3 ms (total creatine), 178 +/- 29 ms (total choline) and 202 +/- 12 ms (N-acetylaspartate). The T2 values of J-coupled metabolites ranged from 89 +/- 8 ms (glutamate) to 148 +/- 14 ms (myo-inositol).