Event-related functional magnetic resonance spectroscopy.

Proton-Magnetic Resonance Spectroscopy (MRS) is a non-invasive brain imaging technique used to measure the concentration of different neurochemicals. "Single-voxel" MRS data is typically acquired across several minutes, before individual transients are averaged through time to give a measurement of neurochemical concentrations. However, this approach is not sensitive to more rapid temporal dynamics of neurochemicals, including those that reflect functional changes in neural computation relevant to perception, cognition, motor control and ultimately behaviour. In this review we discuss recent advances in functional MRS (fMRS) that now allow us to obtain event-related measures of neurochemicals. Event-related fMRS involves presenting different experimental conditions as a series of trials that are intermixed. Critically, this approach allows spectra to be acquired at a time resolution in the order of seconds. Here we provide a comprehensive user guide for event-related task designs, choice of MRS sequence, analysis pipelines, and appropriate interpretation of event-related fMRS data. We raise various technical considerations by examining protocols used to quantify dynamic changes in GABA, the primary inhibitory neurotransmitter in the brain. Overall, we propose that although more data is needed, event-related fMRS can be used to measure dynamic changes in neurochemicals at a temporal resolution relevant to computations that support human cognition and behaviour.

NIfTI-MRS: A standard data format for magnetic resonance spectroscopy.

PURPOSE: Multiple data formats in the MRS community currently hinder data sharing and integration. NIfTI-MRS is proposed as a standard spectroscopy data format, implemented as an extension to the Neuroimaging informatics technology initiative (NIfTI) format. This standardized format can facilitate data sharing and algorithm development as well as ease integration of MRS analysis alongside other imaging modalities. METHODS: A file format using the NIfTI header extension framework incorporates essential spectroscopic metadata and additional encoding dimensions. A detailed description of the specification is provided. An open-source command-line conversion program is implemented to convert single-voxel and spectroscopic imaging data to NIfTI-MRS. Visualization of data in NIfTI-MRS is provided by development of a dedicated plugin for FSLeyes, the FMRIB Software Library (FSL) image viewer. RESULTS: Online documentation and 10 example datasets in the proposed format are provided. Code examples of NIfTI-MRS readers are implemented in common programming languages. Conversion software, spec2nii, currently converts 14 formats where data is stored in image-space to NIfTI-MRS, including Digital Imaging and Communications in Medicine (DICOM) and vendor proprietary formats. CONCLUSION: NIfTI-MRS aims to solve issues arising from multiple data formats being used in the MRS community. Through a single conversion point, processing and analysis of MRS data are simplified, thereby lowering the barrier to use of MRS. Furthermore, it can serve as the basis for open data sharing, collaboration, and interoperability of analysis programs. Greater standardization and harmonization become possible. By aligning with the dominant format in neuroimaging, NIfTI-MRS enables the use of mature tools present in the imaging community, demonstrated in this work by using a dedicated imaging tool, FSLeyes, for visualization.

Age-related decline in cortical inhibitory tone strengthens motor memory.

Ageing disrupts the finely tuned excitation/inhibition balance (E:I) across cortex via a natural decline in inhibitory tone (γ-amino butyric acid, GABA), causing functional decrements. However, in young adults, experimentally lowering GABA in sensorimotor cortex enhances a specific domain of sensorimotor function: adaptation memory. Here, we tested the hypothesis that as sensorimotor cortical GABA declines naturally with age, adaptation memory would increase, and the former would explain the latter. Results confirmed this prediction. To probe causality, we used brain stimulation to further lower sensorimotor cortical GABA during adaptation. Across individuals, how stimulation changed memory depended on sensorimotor cortical E:I. In those with low E:I, stimulation increased memory; in those with high E:I stimulation reduced memory. Thus, we identified a form of motor memory that is naturally strengthened by age, depends causally on sensorimotor cortex neurochemistry, and may be a potent target for motor skill preservation strategies in healthy ageing and neurorehabilitation.

High-resolution metabolic mapping of the cerebellum using 2D zoom magnetic resonance spectroscopic imaging.

PURPOSE: The human cerebellum plays an important role in the functional activity of the cerebrum, ranging from motor to cognitive systems given its relaying role between the spinal cord and cerebrum. The cerebellum poses many challenges to Magnetic Resonance Spectroscopic Imaging (MRSI) due to its caudal location, susceptibility to physiological artifacts, and partial volume artifacts resulting from its complex anatomical structure. Thus, in the present study, we propose a high-resolution MRSI acquisition scheme for the cerebellum. METHODS: A zoom or reduced field of view (rFOV) metabolite-cycled MRSI acquisition at 3 Tesla, with a grid of 48 × 48, was developed to achieve a nominal resolution of 62.5 µL. Single-slice rFOV MRSI data were acquired from the cerebellum of 5 healthy subjects with a nominal resolution of 2.5 × 2.5 × 10 mm3 in 9.6 min. Spectra were quantified using the LCModel package. A spatially unbiased atlas template of the cerebellum was used to analyze metabolite distributions in the cerebellum. RESULTS: The superior quality of the achieved spectra-enabled generation of high-resolution metabolic maps of total N-acetylaspartate, total Creatine (tCr), total Choline (tCho), glutamate+glutamine, and myo-inositol, with Cramér-Rao lower bounds below 50%. A template-based regions of interest (ROI) analysis resulted in spatially dependent metabolite distributions in 9 ROIs. The group-averaged high-resolution metabolite maps across subjects increased the contrast-to-noise ratio between cerebellum regions. CONCLUSION: These findings indicate that very high-resolution metabolite probing of the cerebellum is feasible using rFOV or zoomed MRSI at 3 Tesla.

Fast in vivo 23 Na imaging and T2∗ mapping using accelerated 2D-FID UTE magnetic resonance spectroscopic imaging at 3 T: Proof of concept and reliability study.

PURPOSE: To implement an accelerated MR-acquisition method allowing to map T2∗ relaxation and absolute concentration of sodium within skeletal muscles at 3T. METHODS: A fast-UTE-2D density-weighted concentric-ring-trajectory 23 Na-MRSI technique was used to acquire 64 time points of FID with a spectral bandwidth of 312.5 Hz with an in-plane resolution of 2.5 × 2.5 mm2 in ~15 min. The fast-relaxing 23 Na signal was localized with a single-shot, inversion-recovery-based, non-echo (SIRENE) outer volume suppression (OVS) method. The sequence was verified using simulation and phantom studies before implementing it in human calf muscles. To evaluate the 2D-SIRENE-MRSI (UTE = 0.55 ms) imaging performance, it was compared to a 3D-MRI (UTE = 0.3 ms) sequence. Both data sets were acquired within 2 same-day sessions to assess repeatability. The T2∗ values were fitted voxel-by-voxel using a biexponential model for the 2D-MRSI data. Finally, intra-subject coefficients of variation (CV) were estimated. RESULTS: The MRSI-FID data allowed us to map the fast and slow components of T2∗ in the calf muscles. The spatial distributions of 23 Na concentration for both MRSI and 3D-MRI acquisitions were significantly correlated (P < .001). The test-retest analysis rendered high repeatability for MRSI with a CV of 5%. The mean T2Fast∗ in muscles was 0.7 ± 0.1 ms (contribution fraction = 37%), whereas T2Slow∗ was 13.2 ± 0.2 ms (63%). The mean absolute muscle 23 Na concentration calculated from the T2∗ -corrected data was 28.6 ± 3.3 mM. CONCLUSION: The proposed MRSI technique is a reliable technique to map sodium's absolute concentration and T2∗ within a clinically acceptable scan time at 3T.

Comparison of Neurochemical and BOLD Signal Contrast Response Functions in the Human Visual Cortex.

We investigated the relationship between neurochemical and hemodynamic responses as a function of image contrast in the human primary visual cortex (V1). Simultaneously acquired BOLD-fMRI and single voxel proton MR spectroscopy signals were measured in V1 of 24 healthy human participants of either sex at 7 tesla field strength, in response to presentations (64 s blocks) of different levels of image contrast (3%, 12.5%, 50%, 100%). Our results suggest that complementary measures of neurotransmission and energy metabolism are in partial agreement: BOLD and glutamate signals were linear with image contrast; however, a significant increase in glutamate concentration was evident only at the highest intensity level. In contrast, GABA signals were steady across all intensity levels. These results suggest that neurochemical concentrations are maintained at lower ranges of contrast levels, which match the statistics of natural vision, and that high stimulus intensity may be critical to increase sensitivity to visually modulated glutamate signals in the early visual cortex using MR spectroscopy.SIGNIFICANCE STATEMENT Glutamate and GABA are the major excitatory and inhibitory neurotransmitters of the brain. To better understand the relationship between MRS-visible neurochemicals, the BOLD signal change, and stimulus intensity, we measured combined neurochemical and BOLD signals (combined fMRI-MRS) to different image contrasts in human V1 at 7 tesla. While a linear change to contrast was present for both signals, the increase in glutamate was significant only at the highest stimulus intensity. These results suggest that hemodynamic and neurochemical signals reflect common metabolic markers of neural activity, whereas the mismatch at lower contrast levels may indicate a sensitivity threshold for detecting neurochemical changes during visual processing. Our results highlight the challenge and importance of reconciling cellular and metabolic measures of neural activity in the human brain.

Fat-water separation by fast metabolite cycling magnetic resonance spectroscopic imaging at 3 T: A method to generate separate quantitative distribution maps of musculoskeletal lipid components.

PURPOSE: To provide a rapid, noninvasive fat-water separation technique that allows producing quantitative maps of particular lipid components. METHODS: The calf muscles in 5 healthy adolescents (age 12-16 years; body mass index = 20 ± 3 kg/m2 ) were scanned by two different fat fraction measurement methods. A density-weighted concentric-ring trajectory metabolite-cycling MRSI technique was implemented to collect data with a nominal resolution of 0.25 mL within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data. RESULTS: The proposed MRSI technique provided individual fat fraction maps for eight musculoskeletal lipid components identified by LCModel analysis (IMC/L [CH3 ], EMCL [CH3 ], IMC/L [CH2 ]n , EMC/L [CH2 ]n , IMC/L [CH2 -CH], EMC/L [CH2 -CH], IMC/L [-CH=CH-], and EMC/L [-CH=CH-]) with mean structural similarity indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively, compared with the maps generated by the used Dixon method. Further analysis of voxels with zero structural similarity demonstrated an increased sensitivity of fat fraction lipid maps from the data acquired using this MRSI technique over the standard Dixon technique. The lipid spatial distribution over calf muscles was consistent with previously published findings in adults. CONCLUSION: This MRSI technique can be a useful tool when individual lipid fat fraction maps are desired within a clinically acceptable time and with a nominal spatial resolution of 0.25 mL.

The dynamics of cortical GABA in human motor learning.

KEY POINTS: The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain. Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity. This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement and a period at rest. We report evidence for a reduction in the MRS-measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning. The results provide initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during recovery from stroke. ABSTRACT: The ability to learn novel motor skills is a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7 T magnetic resonance spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, M1 GABA measured early in task performance was strongly correlated with the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order to achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.

Methodological consensus on clinical proton MRS of the brain: Review and recommendations.

Proton MRS (1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.

Neurochemical abnormalities in premanifest and early spinocerebellar ataxias.

OBJECTIVE: To investigate whether early neurochemical abnormalities are detectable by high-field magnetic resonance spectroscopy (MRS) in individuals with spinocerebellar ataxias (SCAs) 1, 2, 3, and 6, including patients without manifestation of ataxia. METHODS: A cohort of 100 subjects (N = 18-21 in each SCA group, including premanifest mutation carriers; mean score on the Scale for the Assessment and Rating of Ataxia [SARA] <10 for all genotypes, and 22 matched controls) was scanned at 7 Tesla to obtain neurochemical profiles of the cerebellum and brainstem. A novel multivariate approach (distance-weighted discrimination) was used to combine regional profiles into an "MRS score." RESULTS: MRS scores robustly distinguished individuals with SCA from controls, with misclassification rates of 0% (SCA2), 2% (SCA3), 5% (SCA1), and 17% (SCA6). Premanifest mutation carriers with estimated disease onset within 10 years had MRS scores in the range of early-manifest SCA subjects. Levels of neuronal and glial markers significantly correlated with SARA and an Activities of Daily Living score in subjects with SCA. Regional neurochemical alterations were different between SCAs at comparable disease severity, with SCA2 displaying the most extensive neurochemical abnormalities, followed by SCA1, SCA3, and SCA6. INTERPRETATION: Neurochemical abnormalities are detectable in individuals before manifest disease, which may allow premanifest enrollment in future SCA trials. Correlations with ataxia and quality-of-life scores show that neurochemical levels can serve as clinically meaningful endpoints in trials. Ranking of SCA types by degree of neurochemical abnormalities indicates that the neurochemistry may reflect synaptic function or density. Ann Neurol 2018;83:816-829.

MRS and DTI evidence of progressive posterior cingulate cortex and corpus callosum injury in the hyper-acute phase after Traumatic Brain Injury.

The posterior cingulate cortex (PCC) and corpus callosum (CC) are susceptible to trauma, but injury often evades detection. PCC Metabolic disruption may predict CC white matter tract injury and the secondary cascade responsible for progression. While the time frame for the secondary cascade remains unclear in humans, the first 24 h (hyper-acute phase) are crucial for life-saving interventions. Objectives: To test whether Magnetic Resonance Imaging (MRI) markers are detectable in the hyper-acute phase and progress after traumatic brain injury (TBI) and whether alterations in these parameters reflect injury severity. Methods: Spectroscopic and diffusion-weighted MRI data were collected in 18 patients with TBI (within 24 h and repeated 7-15 days following injury) and 18 healthy controls (scanned once). Results: Within 24 h of TBI N-acetylaspartate was reduced (F = 11.43, p = 0.002) and choline increased (F = 10.67, p = 0.003), the latter driven by moderate-severe injury (F = 5.54, p = 0.03). Alterations in fractional anisotropy (FA) and axial diffusivity (AD) progressed between the two time-points in the splenium of the CC (p = 0.029 and p = 0.013). Gradual reductions in FA correlated with progressive increases in choline (p = 0.029). Conclusions: Metabolic disruption and structural injury can be detected within hours of trauma. Metabolic and diffusion parameters allow identification of severity and provide evidence of injury progression.

Density-weighted concentric rings k-space trajectory for 1 H magnetic resonance spectroscopic imaging at 7 T.

It has been shown that density-weighted (DW) k-space sampling with spiral and conventional phase encoding trajectories reduces spatial side lobes in magnetic resonance spectroscopic imaging (MRSI). In this study, we propose a new concentric ring trajectory (CRT) for DW-MRSI that samples k-space with a density that is proportional to a spatial, isotropic Hanning window. The properties of two different DW-CRTs were compared against a radially equidistant (RE) CRT and an echo-planar spectroscopic imaging (EPSI) trajectory in simulations, phantoms and in vivo experiments. These experiments, conducted at 7 T with a fixed nominal voxel size and matched acquisition times, revealed that the two DW-CRT designs improved the shape of the spatial response function by suppressing side lobes, also resulting in improved signal-to-noise ratio (SNR). High-quality spectra were acquired for all trajectories from a specific region of interest in the motor cortex with an in-plane resolution of 7.5 × 7.5 mm2 in 8 min 3 s. Due to hardware limitations, high-spatial-resolution spectra with an in-plane resolution of 5 × 5 mm2 and an acquisition time of 12 min 48 s were acquired only for the RE and one of the DW-CRT trajectories and not for EPSI. For all phantom and in vivo experiments, DW-CRTs resulted in the highest SNR. The achieved in vivo spectral quality of the DW-CRT method allowed for reliable metabolic mapping of eight metabolites including N-acetylaspartylglutamate, γ-aminobutyric acid and glutathione with Cramér-Rao lower bounds below 50%, using an LCModel analysis. Finally, high-quality metabolic mapping of a whole brain slice using DW-CRT was achieved with a high in-plane resolution of 5 × 5 mm2 in a healthy subject. These findings demonstrate that our DW-CRT MRSI technique can perform robustly on MRI systems and within a clinically feasible acquisition time.

A comparison of 2-hydroxyglutarate detection at 3 and 7 T with long-TE semi-LASER.

Abnormally high levels of the 'oncometabolite' 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field (≥7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection. Long echo time (long-TE) semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) is a promising method for improved 2-HG detection in vivo at either 3 or 7 T owing to the use of broad-band adiabatic localization. Using previously published semi-LASER methods at 3 and 7 T, this study directly compares the detectability of 2-HG in phantoms and in vivo across nine patients. Cramér-Rao lower bounds (CRLBs) of 2-HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild-type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2-HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ-aminobutyric acid (GABA) and 2-HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2-HG detection using long-TE acquisition at 7 T may allow for more rapid estimation of 2-HG (within a few spectral averages) together with other associated metabolic markers in glioma.

Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla.

BACKGROUND: The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5-3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine. METHOD: We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference. RESULTS: Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001). CONCLUSIONS: The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain.

Combined fMRI-MRS is a novel method to non-invasively investigate functional activation in the human brain using simultaneous acquisition of hemodynamic and neurochemical measures. The aim of the current study was to quantify neural activity using combined fMRI-MRS at 7T. BOLD-fMRI and semi-LASER localization MRS data were acquired from the visual cortex of 13 participants during short blocks (64s) of flickering checkerboards. We demonstrate a correlation between glutamate and BOLD-fMRI time courses (R=0.381, p=0.031). In addition, we show increases in BOLD-fMRI (1.43±0.17%) and glutamate concentrations (0.15±0.05 I.U., ~2%) during visual stimulation. In contrast, we observed no change in glutamate concentrations in resting state MRS data during sham stimulation periods. Spectral line width changes generated by the BOLD-response were corrected using line broadening. In summary, our results establish the feasibility of concurrent measurements of BOLD-fMRI and neurochemicals using a novel combined fMRI-MRS sequence. Our findings strengthen the link between glutamate and functional activity in the human brain by demonstrating a significant correlation of BOLD-fMRI and glutamate over time, and by showing ~2% glutamate increases during 64s of visual stimulation. Our tool may become useful for studies characterizing functional dynamics between neurochemicals and hemodynamics in health and disease.

Non-water-suppressed short-echo-time magnetic resonance spectroscopic imaging using a concentric ring k-space trajectory.

Water-suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non-water-suppressed MRS spectrum is used for artefact correction, reconstruction of phased-array coil data and metabolite quantification. Here, a two-scan metabolite-cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short-echo (TE  = 14 ms), two-dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite-cycling is counterbalanced by a time-efficient concentric ring k-space trajectory. To validate the technique, water-suppressed MRSI acquisitions were also performed for comparison. The proposed non-water-suppressed metabolite-cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high-resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non-water-suppressed and water-suppressed techniques. The achieved spectral quality, signal-to-noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in-plane resolution of 10 × 10 mm2 in 8 min and with a Cramér-Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non-water-suppressed technique enabled voxel-wise single-scan frequency, phase and eddy current correction. These findings demonstrate that our non-water-suppressed metabolite-cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.

Test-retest reproducibility of neurochemical profiles with short-echo, single-voxel MR spectroscopy at 3T and 7T.

PURPOSE: To determine the test-retest reproducibility of neurochemical concentrations obtained with a highly optimized, short-echo, single-voxel proton MR spectroscopy (MRS) pulse sequence at 3T and 7T using state-of-the-art hardware. METHODS: A semi-LASER sequence (echo time = 26-28 ms) was used to acquire spectra from the posterior cingulate and cerebellum at 3T and 7T from six healthy volunteers who were scanned four times weekly on both scanners. Spectra were quantified with LCModel. RESULTS: More neurochemicals were quantified with mean Cramér-Rao lower bounds (CRLBs) ≤20% at 7T than at 3T despite comparable frequency-domain signal-to-noise ratio. Whereas CRLBs were lower at 7T (P < 0.05), between-session coefficients of variance (CVs) were comparable at the two fields with 64 transients. Five metabolites were quantified with between-session CVs ≤5% at both fields. Analysis of subspectra showed that a minimum achievable CV was reached with a lower number of transients at 7T for multiple metabolites and that between-session CVs were lower at 7T than at 3T with fewer than 64 transients. CONCLUSION: State-of-the-art MRS methodology allows excellent reproducibility for many metabolites with 5-min data averaging on clinical 3T hardware. Sensitivity and resolution advantages at 7T are important for weakly represented metabolites, short acquisitions, and small volumes of interest. Magn Reson Med 76:1083-1091, 2016. © 2015 Wiley Periodicals, Inc.

Neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral anophthalmia.

Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex, (1)H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests that the lack of visual input from the eyes might have delayed or arrested the maturation of this cortical region. High levels of choline and glutamate/glutamine are consistent with enhanced excitatory circuits in the anophthalmic occipital cortex, which could reflect a shift toward enhanced plasticity or sensitivity that could in turn mediate or unmask cross-modal responses. Finally, it is possible that the change in function of the occipital cortex results in biochemical profiles that resemble those of auditory, language, or somatosensory cortex.

Two-site reproducibility of cerebellar and brainstem neurochemical profiles with short-echo, single-voxel MRS at 3T.

PURPOSE: To determine whether neurochemical concentrations obtained at two MRI sites using clinical 3T scanners can be pooled when a highly optimized, nonvendor short-echo, single-voxel proton MRS pulse sequence is used in conjunction with identical calibration and quantification procedures. METHODS: A modified semi-LASER sequence (TE = 28 ms) was used to acquire spectra from two brain regions (cerebellar vermis and pons) on two Siemens 3T scanners using the same B0 and B1 calibration protocols from two different cohorts of healthy volunteers (N = 24-33 per site) matched for age and body mass index. Spectra were quantified with LCModel using water scaling. RESULTS: The spectral quality was very consistent between the two sites and allowed reliable quantification of at least 13 metabolites in the vermis and pons compared with 3-5 metabolites in prior multisite magnetic resonance spectroscopy trials using vendor-provided sequences. The neurochemical profiles were nearly identical at the two sites and showed the feasibility to detect interindividual differences in the healthy brain. CONCLUSION: Highly reproducible neurochemical profiles can be obtained on different clinical 3T scanners at different sites, provided that the same, optimized acquisition and analysis techniques are used. This will allow pooling of multisite data in clinical studies, which is particularly critical for rare neurological diseases.

Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3 T.

Hippocampal dysfunction is known to be associated with several neurological and neuropsychiatric disorders such as Alzheimer's disease, epilepsy, schizophrenia and depression; therefore, there has been significant clinical interest in studying hippocampal neurochemistry. However, the hippocampus is a challenging region to study using (1) H MRS, hence the use of MRS for clinical research in this region has been limited. Our goal was therefore to investigate the feasibility of obtaining high-quality hippocampal spectra that allow reliable quantification of a neurochemical profile and to establish inter-session reproducibility of hippocampal MRS, including reproducibility of voxel placement, spectral quality and neurochemical concentrations. Ten healthy volunteers were scanned in two consecutive sessions using a standard clinical 3 T MR scanner. Neurochemical profiles were obtained with a short-echo (T(E) = 28 ms) semi-LASER localization sequence from a relatively small (~4 mL) voxel that covered about 62% of the hippocampal volume as calculated from segmentation of T1 -weighted images. Voxel composition was highly reproducible between sessions, with test-retest coefficients of variation (CVs) of 3.5% and 7.5% for gray and white matter volume fraction, respectively. Excellent signal-to-noise ratio (~54 based on the N-acetylaspartate (NAA) methyl peak in non-apodized spectra) and linewidths (~9 Hz for water) were achieved reproducibly in all subjects. The spectral quality allowed quantification of NAA, total choline, total creatine, myo-inositol and glutamate with high scan-rescan reproducibility (CV ≤ 6%) and quantification precision (Cramér-Rao lower bound, CRLB < 9%). Four other metabolites, including glutathione and glucose, were quantified with scan-rescan CV below 20%. Therefore, the highly optimized, short-echo semi-LASER sequence together with FASTMAP shimming substantially improved the reproducibility and number of quantifiable metabolites relative to prior reports. In addition, the between-session variation in metabolite concentrations, as well as CRLB, was lower than the between-subject variation of the concentrations for most metabolites, indicating that the method has the sensitivity to detect inter-individual differences in the healthy brain.