Reproducibility of cerebral perfusion measurements using BOLD delay.

BOLD delay is an emerging, noninvasive method for assessing cerebral perfusion that does not require the use of intravenous contrast agents and is thus particularly suited for longitudinal monitoring. In this study, we assess the reproducibility of BOLD delay using data from 136 subjects with normal cerebral perfusion scanned on two separate occasions with scanners, sequence parameters, and intervals between scans varying between subjects. The effects of various factors on the reproducibility of BOLD delay, defined here as the differences in BOLD delay values between the scanning sessions, were investigated using a linear mixed model. Reproducibility was additionally assessed using the intraclass correlation coefficient of BOLD delay between sessions. Reproducibility was highest in the posterior cerebral artery territory. The mean BOLD delay test-retest difference after accounting for the aforementioned factors was 1.2 s (95% CI = 1.0 to 1.4 s). Overall, BOLD delay shows good reproducibility, but care should be taken when interpreting longitudinal BOLD delay changes that are either very small or are located in certain brain regions.

Fourier-based decomposition for simultaneous 2-voxel MRS acquisition with 2SPECIAL.

PURPOSE: To simultaneously acquire spectroscopic signals from two MRS voxels using a multi-banded 2 spin-echo, full-intensity acquired localized (2SPECIAL) sequence, and to decompose the signal to their respective regions by a novel voxel-GRAPPA (vGRAPPA) decomposition approach for in vivo brain applications at 7 T. METHODS: A wideband, uniform rate, smooth truncation (WURST) multi-banded pulse was incorporated into SPECIAL to implement 2SPECIAL for simultaneous multi-voxel spectroscopy (sMVS). To decompose the acquired data, the voxel-GRAPPA decomposition algorithm is introduced, and its performance is compared to the SENSE-based decomposition. Furthermore, the limitations of two-voxel excitation concerning the multi-banded adiabatic inversion pulse, as well as of the combined B0 shim and B1 + adjustments, are evaluated. RESULTS: It was successfully shown that the 2SPECIAL sequence enables sMVS without a significant loss in SNR while reducing the total scan time by 21.6% compared to two consecutive acquisitions. The proposed voxel-GRAPPA algorithm properly reassigns the signal components to their respective origin region and shows no significant differences to the well-established SENSE-based algorithm in terms of leakage (both <10%) or Cramér-Rao lower bounds (CRLB) for in vivo applications, while not requiring the acquisition of additional sensitivity maps and thus decreasing motion sensitivity. CONCLUSION: The use of 2SPECIAL in combination with the novel voxel-GRAPPA decomposition technique allows a substantial reduction of measurement time compared to the consecutive acquisition of two single voxels without a significant decrease in spectral quality or metabolite quantification accuracy and thus provides a new option for multiple-voxel applications.

Assessment of measurement precision in single-voxel spectroscopy at 7 T: Toward minimal detectable changes of metabolite concentrations in the human brain in vivo.

PURPOSE: To introduce a study design and statistical analysis framework to assess the repeatability, reproducibility, and minimal detectable changes (MDCs) of metabolite concentrations determined by in vivo MRS. METHODS: An unbalanced nested study design was chosen to acquire in vivo MRS data within different repeatability and reproducibility scenarios. A spin-echo, full-intensity acquired localized (SPECIAL) sequence was employed at 7 T utlizing three different inversion pulses: a hyperbolic secant (HS), a gradient offset independent adiabaticity (GOIA), and a wideband, uniform rate, smooth truncation (WURST) pulse. Metabolite concentrations, Cramér-Rao lower bounds (CRLBs) and coefficients of variation (CVs) were calculated. Both Bland-Altman analysis and a restricted maximum-likelihood estimation (REML) analysis were performed to estimate the different variance contributions of the repeatability and reproducibility of the measured concentration. A Bland-Altmann analysis of the spectral shape was performed to assess the variance of the spectral shape, independent of quantification model influences. RESULTS: For the used setup, minimal detectable changes of brain metabolite concentrations were found to be between 0.40 µmol/g and 2.23 µmol/g. CRLBs account for only 16 % to 74 % of the total variance of the metabolite concentrations. The application of gradient-modulated inversion pulses in SPECIAL led to slightly improved repeatability, but overall reproducibility appeared to be limited by differences in positioning, calibration, and other day-to-day variations throughout different sessions. CONCLUSION: A framework is introduced to estimate the precision of metabolite concentrations obtained by MRS in vivo, and the minimal detectable changes for 13 metabolite concentrations measured at 7 T using SPECIAL are obtained.

Contribution of macromolecules to brain 1 H MR spectra: Experts' consensus recommendations.

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.

T2 relaxation times of macromolecules and metabolites in the human brain at 9.4 T.

PURPOSE: Relaxation times can contribute to spectral assignment. In this study, effective T2 relaxation times ( T2eff ) of macromolecules are reported for gray and white matter-rich voxels in the human brain at 9.4 T. The T2eff of macromolecules are helpful to understand their behavior and the effect they have on metabolite quantification. Additionally, for absolute quantification of metabolites with magnetic resonance spectroscopy, appropriate T2 values of metabolites must be considered. The T2 relaxation times of metabolites are calculated after accounting for TE/sequence-specific macromolecular baselines. METHODS: Macromolecular and metabolite spectra for a series of TEs were acquired at 9.4 T using double inversion-recovery metabolite-cycled semi-LASER and metabolite-cycled semi-LASER, respectively. The T2 relaxation times were calculated by fitting the LCModel relative amplitudes of macromolecular peaks and metabolites to a mono-exponential decay across the TE series. Furthermore, absolute concentrations of metabolites were calculated using the estimated relaxation times and internal water as reference. RESULTS: The T2eff of macromolecules are reported, which range from 13 ms to 40 ms, whereas, for metabolites, they range from 40 ms to 110 ms. Both macromolecular and metabolite T2 relaxation times are observed to follow the decreasing trend, with increasing B0 . The linewidths of metabolite singlets can be fully attributed to T2 and B0 components. However, in addition to these components, macromolecule linewidths have contributions from J-coupling and overlapping resonances. CONCLUSION: The T2 relaxation times of all macromolecular and metabolite peaks at 9.4 T in vivo are reported for the first time. Metabolite relaxation times were used to calculate the absolute metabolite concentrations.

Advanced single voxel 1 H magnetic resonance spectroscopy techniques in humans: Experts' consensus recommendations.

Conventional proton MRS has been successfully utilized to noninvasively assess tissue biochemistry in conditions that result in large changes in metabolite levels. For more challenging applications, namely, in conditions which result in subtle metabolite changes, the limitations of vendor-provided MRS protocols are increasingly recognized, especially when used at high fields (≥3 T) where chemical shift displacement errors, B0 and B1 inhomogeneities and limitations in the transmit B1 field become prominent. To overcome the limitations of conventional MRS protocols at 3 and 7 T, the use of advanced MRS methodology, including pulse sequences and adjustment procedures, is recommended. Specifically, the semiadiabatic LASER sequence is recommended when TE values of 25-30 ms are acceptable, and the semiadiabatic SPECIAL sequence is suggested as an alternative when shorter TE values are critical. The magnetic field B0 homogeneity should be optimized and RF pulses should be calibrated for each voxel. Unsuppressed water signal should be acquired for eddy current correction and preferably also for metabolite quantification. Metabolite and water data should be saved in single shots to facilitate phase and frequency alignment and to exclude motion-corrupted shots. Final averaged spectra should be evaluated for SNR, linewidth, water suppression efficiency and the presence of unwanted coherences. Spectra that do not fit predefined quality criteria should be excluded from further analysis. Commercially available tools to acquire all data in consistent anatomical locations are recommended for voxel prescriptions, in particular in longitudinal studies. To enable the larger MRS community to take advantage of these advanced methods, a list of resources for these advanced protocols on the major clinical platforms is provided. Finally, a set of recommendations are provided for vendors to enable development of advanced MRS on standard platforms, including implementation of advanced localization sequences, tools for quality assurance on the scanner, and tools for prospective volume tracking and dynamic linear shim corrections.

Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration.

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia. OBJECTIVES: The aim of this study was to quantify iron concentrations in deep gray matter structures using quantitative susceptibility mapping MRI and to characterize metabolic abnormalities in the pyramidal pathway using 1 H MR spectroscopy in clinically manifesting membrane protein-associated neurodegeneration patients and asymptomatic C19orf12 gene mutation heterozygous carriers. METHODS: We present data of 4 clinically affected membrane protein-associated neurodegeneration patients (mean age: 21.0 ± 2.9 years) and 9 heterozygous gene mutation carriers (mean age: 50.4 ± 9.8 years), compared to age-matched healthy controls. MRI assessments were performed on a 7.0 Tesla whole-body system, consisting of whole-brain gradient-echo scans and short echo time, single-volume MR spectroscopy in the white matter of the precentral/postcentral gyrus. Quantitative susceptibility mapping, a surrogate marker for iron concentration, was performed using a state-of-the-art multiscale dipole inversion approach with focus on the globus pallidus, thalamus, putamen, caudate nucleus, and SN. RESULTS AND CONCLUSION: In membrane protein-associated neurodegeneration patients, magnetic susceptibilities were 2 to 3 times higher in the globus pallidus (P = 0.02) and SN (P = 0.02) compared to controls. In addition, significantly higher magnetic susceptibility was observed in the caudate nucleus (P = 0.02). Non-manifesting heterozygous mutation carriers exhibited significantly increased magnetic susceptibility (relative to controls) in the putamen (P = 0.003) and caudate nucleus (P = 0.001), which may be an endophenotypic marker of genetic heterozygosity. MR spectroscopy revealed significantly increased levels of glutamate, taurine, and the combined concentration of glutamate and glutamine in membrane protein-associated neurodegeneration, which may be a correlate of corticospinal pathway dysfunction frequently observed in membrane protein-associated neurodegeneration patients. © 2019 International Parkinson and Movement Disorder Society.

Metabolite-cycled STEAM and semi-LASER localization for MR spectroscopy of the human brain at 9.4T.

PURPOSE: Metabolite cycling (MC) is an MRS technique for the simultaneous acquisition of water and metabolite spectra that avoids chemical exchange saturation transfer effects and for which water may serve as a reference signal or contain additional information in functional or diffusion studies. Here, MC was developed for human investigations at ultrahigh field. METHODS: MC-STEAM and MC-semi-LASER are introduced at 9.4T with an optimized inversion pulse and elaborate coil setup. Experimental and simulation results are given for the implementation of adiabatic inversion pulses for MC. The two techniques are compared, and the effect of frequency and phase correction based on the MC water spectra is evaluated. Finally, absolute quantification of metabolites is performed. RESULTS: The proposed coil configuration results in a maximum B1 + of 48 µΤ in a voxel within the occipital lobe. Frequency and phase correction of single acquisitions improve signal-to-noise ratio (SNR) and linewidth, leading to high-resolution spectra. The improvement of SNR of N-acetylaspartate (SNRNAA ) for frequency aligned data, acquired with MC-STEAM and MC-semi-LASER, are 37% and 30%, respectively (P < 0.05). Moreover, a doubling of the SNRNAA for MC-semi-LASER in comparison with MC-STEAM is observed (P < 0.05). Concentration levels for 18 metabolites from the human occipital lobe are reported, as acquired with both MC-STEAM and MC-semi-LASER. CONCLUSION: This work introduces a novel methodology for single-voxel MRS on a 9.4T whole-body scanner and highlights the advantages of semi-LASER compared to STEAM in terms of excitation profile. In comparison with MC-STEAM, MC-semi-LASER yields spectra with higher SNR. Magn Reson Med 79:1841-1850, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

In vivo characterization of the downfield part of 1 H MR spectra of human brain at 9.4 T: Magnetization exchange with water and relation to conventionally determined metabolite content.

PURPOSE: To perform exchange-rate measurements on the in vivo human brain downfield spectrum (5-10 ppm) at 9.4 T and to compare the variation in concentrations of the downfield resonances and of known upfield metabolites to determine potential peak labels. METHODS: Non-water-suppressed metabolite cycling was used in combination with an inversion transfer technique in two brain locations in healthy volunteers to measure the exchange rates and T1 values of exchanging peaks. Spectra were fitted with a heuristic model of a series of 13 or 14 Voigt lines, and a Bloch-McConnell model was used to fit the exchange rate curves. Concentrations from non-water-inverted spectra upfield and downfield were compared. RESULTS: Mean T1 values ranged from 0.40 to 0.77 s, and exchange rates from 0.74 to 13.8 s-1 . There were no significant correlations between downfield and upfield concentrations, except for N-acetylaspartate, with a correlation coefficient of 0.63 and P < 0.01. CONCLUSIONS: Using ultrahigh field allowed improved separation of peaks in the 8.2 to 8.5 ppm amide proton region, and the exchange rates of multiple downfield resonances including the 5.8-ppm peak, previously tentatively assigned to urea, were measured in vivo in human brain. Downfield peaks consisted of overlapping components, and largely missing correlations between upfield and downfield resonances-although not conclusive-indicate limited contributions from metabolites present upfield to the downfield spectrum. Magn Reson Med 79:2863-2873, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Effect of age and the APOE gene on metabolite concentrations in the posterior cingulate cortex.

Proton magnetic resonance spectroscopy (1H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm3 voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years). All 1H-MRS scans were performed at 3T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in 1H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample.

Towards a neurochemical profile of the amygdala using short-TE 1 H 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.

Detection of metabolite changes in response to a varying visual stimulation paradigm using short-TE 1 H MRS at 7 T.

The two-fold benefit of 1 H magnetic resonance spectroscopy (MRS) at high B0 fields - enhanced sensitivity and increased spectral dispersion - has been used previously to study dynamic changes in metabolite concentrations in the human brain in response to visual stimulation. In these studies, a strong visual on/off stimulus was combined with MRS data acquisition in a voxel location in the occipital cortex determined by an initial functional magnetic resonance imaging experiment. However, 1) to exclude the possibility of systemic effects (heartbeat, blood flow, etc.), which tend to be different for on/off conditions, a modified stimulation condition not affecting the target voxel needs to be employed, and 2) to assess important neurotransmitters of low concentration, in particular γ-aminobutyric acid (GABA), it may be advantageous to analyze steady-state, rather than dynamic, conditions. Thus, the aim of this study was to use short-TE 1 H MRS methodology at 7 T to detect differences in steady-state metabolite levels in response to a varying stimulation paradigm in the human visual cortex. The two different stimulation conditions were termed voxel and control activation. Localized MR spectra were acquired using the SPECIAL (spin-echo full-intensity acquired localized) sequence. Data were analyzed using LCModel. Fifteen individual metabolites were reliably quantified. On comparison of steady-state concentrations for voxel versus control activation, a decrease in GABA of 0.05 mmol/L (5%) and an increase in lactate of 0.04 mmol/L (7%) were found to be the only significant effects. The observed reduction in GABA can be interpreted as reduced neuronal inhibition during voxel activation, whereas the increase in lactate hints at an intensification of anaerobic glycolysis. Differences from previous studies, notably the absence of any changes in glutamate, are attributed to the modified experimental conditions. This study demonstrates that the use of advanced 1 H MRS methodology at 7 T allows the detection of subtle changes in metabolite concentrations involved in neuronal activation and inhibition.

GABA concentration in superior temporal sulcus predicts gamma power and perception in the sound-induced flash illusion.

In everyday life we are confronted with inputs of multisensory stimuli that need to be integrated across our senses. Individuals vary considerably in how they integrate multisensory information, yet the neurochemical foundations underlying this variability are not well understood. Neural oscillations, especially in the gamma band (>30Hz) play an important role in multisensory processing. Furthermore, gamma-aminobutyric acid (GABA) neurotransmission contributes to the generation of gamma band oscillations (GBO), which can be sustained by activation of metabotropic glutamate receptors. Hence, differences in the GABA and glutamate systems might contribute to individual differences in multisensory processing. In this combined magnetic resonance spectroscopy and electroencephalography study, we examined the relationships between GABA and glutamate concentrations in the superior temporal sulcus (STS), source localized GBO, and illusion rate in the sound-induced flash illusion (SIFI). In 39 human volunteers we found robust relationships between GABA concentration, GBO power, and the SIFI perception rate (r-values=0.44 to 0.53). The correlation between GBO power and SIFI perception rate was about twofold higher when the modulating influence of the GABA level was included in the analysis as compared to when it was excluded. No significant effects were obtained for glutamate concentration. Our study suggests that the GABA level shapes individual differences in audiovisual perception through its modulating influence on GBO. GABA neurotransmission could be a promising target for treatment interventions of multisensory processing deficits in clinical populations, such as schizophrenia or autism.

A new sequence for shaped voxel spectroscopy in the human brain using 2D spatially selective excitation and parallel transmission.

Spatially selective excitation in two dimensions (2D-SSE) utilizing parallel transmission was applied as a means to acquire signal from voxels adapted to the anatomy of interest for in vivo (1) H MR spectroscopy. A novel method to select spectroscopy voxels with arbitrary shapes in two dimensions was investigated. An on-off scheme with an adiabatic slice selective inversion pulse preceding a 2D-SSE pulse together with a segmented inward spiral excitation k-space trajectory enabled rapid free induction decay acquisitions. Performance of the sequence was evaluated in simulations, phantom experiments, and in vivo measurements at 3 T. High spatial fidelity of the excitation profile was achieved for different target shapes and with little off-resonance deterioration. Metabolite concentrations in human brain determined with the new sequence were quantified with Cramér-Rao lower bounds less than 20%. They were in the physiological range and did not deviate systematically from results acquired with a conventional SPECIAL sequence. In conclusion, a new approach for shaped voxel MRS in the human brain is presented, which complements existing sequences. Simulations show that 2D-SSE pulses yield reduced chemical shift artifact when compared with conventional localization methods. Copyright © 2016 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 (1)H/(19)F MR of the human knee at 7.0 T following application of (19)F-containing drugs. The (1)H/(19)F RF coil array includes a posterior module with two (1)H loop elements and two anterior modules, each consisting of one (1)H and two (19)F 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 (19)F MRS was conducted with 47 and 101 mmol/L of flufenamic acid (FA) ­ a (19)F-containing non-steroidal anti-inflammatory drug ­ to determine T1 and T2 and to study the (19)F signal-to-dose relationship. The suitability of the proposed approach for (1)H/(19)F 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) mm(2) 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 (1)H/(19)F 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 (19)F-containing medicinal compounds in vivo.

Simultaneous dual contrast weighting using double echo rapid acquisition with relaxation enhancement (RARE) imaging.

PURPOSE: This work proposes a dual contrast rapid acquisition with relaxation enhancement (RARE) variant (2in1-RARE), which provides simultaneous proton density (PD) and T2 * contrast in a single acquisition. THEORY AND METHODS: The underlying concept of 2in1-RARE is the strict separation of spin echoes and stimulated echoes. This approach offers independent weighting of spin echoes and stimulated echoes. 2in1-RARE was evaluated in phantoms including signal-to-noise ratio (SNR) and point spread function assessment. 2in1-RARE was benchmarked versus coherent RARE and a split-echo RARE variant. The applicability of 2in1-RARE for brain imaging was demonstrated in a small cohort of healthy subjects (n = 10) and, exemplary, a multiple sclerosis patient at 3 Tesla as a precursor to a broader clinical study. RESULTS: 2in1-RARE enables the simultaneous acquisition of dual contrast weighted images without any significant image degradation and without sacrificing SNR versus split-echo RARE. This translates into a factor of two speed gain over multi-contrast, sequential split-echo RARE. A 15% broadening of the point spread function was observed in 2in1-RARE. T1 relaxation effects during the mixing time can be neglected for brain tissue. CONCLUSION: 2in1-RARE offers simultaneous acquisition of images of anatomical (PD) and functional (T2 *) contrast. It presents an alternative to address scan time constraints frequently encountered during sequential acquisition of T2 * or PD-weighted RARE.

Net increase of lactate and glutamate concentration in activated human visual cortex detected with magnetic resonance spectroscopy at 7 tesla.

After the landmark studies reporting changes in the cerebral metabolic rate of glucose (CMRGlc ) in excess of those in oxygen (CMRO2 ) during physiological stimulation, several studies have examined the fate of the extra carbon taken up by the brain, reporting a wide range of changes in brain lactate from 20% to 250%. The present study reports functional magnetic resonance spectroscopy measurements at 7 Tesla using the enhanced sensitivity to study a small cohort (n = 6). Small increases in lactate (19% ± 4%, P < 0.05) and glutamate (4% ± 1%, P < 0.001) were seen within the first 2 min of activation. With the exception of glucose (12% ± 5%, P < 0.001), no other metabolite concentration changes beyond experimental error were significantly observed. Therefore, the present study confirms that lactate and glutamate changes during physiological stimulation are small (i.e. below 20%) and shows that the increased sensitivity allows reproduction of previous results with fewer subjects. In addition, the initial rate of glutamate and lactate concentration increases implies an increase in CMRO2 that is slightly below that of CMRGlc during the first 1-2 min of activation.

Unedited in vivo detection and quantification of γ-aminobutyric acid in the occipital cortex using short-TE MRS at 3 T.

Short-TE MRS has been proposed recently as a method for the in vivo detection and quantification of γ-aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short-TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal-to-noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal-to-noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short-TE MRS in the occipital cortex of 14 healthy volunteers. Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within-session reproducibility was assessed in the same 14 subjects using four consecutive short-TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 ± 4.9%. This study demonstrates that, under some experimental conditions, short-TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions.

Magnetization transfer-based 3D visualization of foot peripheral nerves.

PURPOSE: To investigate magnetization transfer (MT) effects as a new source of contrast for imaging and tracking of peripheral foot nerves. MATERIALS AND METHODS: Two sets of 3D spoiled gradient-echo images acquired with and without a saturation pulse were used to generate MT ratio (MTR) maps of 260 µm in-plane resolution for eight volunteers at 3T. Scan parameters were adjusted to minimize signal loss due to T2 dephasing, and a dedicated coil was used to improve the inherently low signal-to-noise ratio of small voxels. Resulting MTR values in foot nerves were compared with those in surrounding muscle tissue. RESULTS: Average MTR values for muscle (45.5 ± 1.4%) and nerve (21.4 ± 3.1%) were significantly different (P < 0.0001). In general, the difference in MTR values was sufficiently large to allow for intensity-based segmentation and tracking of foot nerves in individual subjects. This procedure was termed MT-based 3D visualization. CONCLUSION: The MTR serves as a new source of contrast for imaging of peripheral foot nerves and provides a means for high spatial resolution tracking of these structures. The proposed methodology is directly applicable on standard clinical MR scanners and could be applied to systemic pathologies, such as diabetes.