MRS Voxel Research Articles

On the impact of B0 shimming algorithms on single-voxel MR spectroscopy.

To assess the impact of different B0 shimming algorithms on MRS. B0 field maps and single-voxel MR spectroscopy were acquired in the prefrontal cortex of five volunteers at 3 T using five different B0 shimming approaches. B0 shimming was achieved using Siemens' proprietary shim algorithm, in addition to the Pseudo-Inverse (PI), Quadratic Programming (QuadProg), Least Squares (LSq), and Gradient optimization (Grad) algorithms. The standard deviation of the shimmed B0 field, as well as the SNR and FWHM of the measured metabolites, was used to evaluate the performance of each B0 shimming algorithm. Compared to Siemens's shim, significant reductions (p < 0.01) in the standard deviation of the B0 field distribution within the MRS voxel were observed for the PI, QuadProg, and Grad algorithms (3.8 Hz, 7.3 Hz, and 3.9 Hz respectively, compared to 11.5 Hz for Siemens), but not for the LSq (12.9 Hz) algorithm. Moreover, significantly increased SNR and reduced FWHM for the N-acetylaspartate metabolite were consistent with the improvement in B0 homogeneity for the aforementioned shimming algorithms. Here, we demonstrate that the choice of B0 shimming algorithm can have a significant impact on the quality of MR spectra and that significant improvements in spectrum quality could be achieved by using alternatives to the default vendor approach.

B0-insensitive image navigators for prospective motion-corrected MRS with localized second-order shimming.

Localized shimming in single-voxel MRS often results in large B0 inhomogeneity outside the volume-of-interest. This causes unacceptable degradation in motion navigator images. Switching back and forth between whole-brain shim and localized shim is possible for linear shims, but not for higher-order shims. Here we propose motion navigators largely insensitive to B0 inhomogeneity for prospective motion-corrected MRS with localized higher-order shimming. A recent fast high-resolution motion navigator based on spiral-in/out k-space trajectories and multislice-to-volume registration was modified by splitting the readout into multiple shot interleaves which shortened the echo time and reduced the effect of B0 inhomogeneity. The performance of motion correction was assessed in healthy subjects in the prefrontal cortex using a sLASER sequence at 3T (N = 5) and 7T (N = 5). With multiple spatial interleaves, excellent quality navigator images were acquired in the whole brain in spite of large B0 inhomogeneity outside the MRS voxel. The total duration of the navigator in sLASER remained relatively short even with multiple shots (3T: 10 spatial interleaves 94 ms per slice; 7T: 15 spatial interleaves 103 ms per slice). Prospective motion correction using the multi-shot navigators yielded comparable spectral quality (water linewidth and metabolite SNR) with and without subject motion. B0-insensitive motion navigators enable prospective motion correction for MRS with all first- and second-order shims adjusted in the MRS voxel, providing optimal spectral linewidth.

A 7T interleaved fMRS and fMRI study on visual contrast dependency in the human brain

Abstract Introduction: Functional magnetic resonance spectroscopy (fMRS) is a non-invasive technique for measuring dynamic changes in neurometabolites. While previous studies have observed concentration changes in metabolites during neural activation, the relationship between neurometabolite response and stimulus intensity and timing requires further investigation. To address this, we conducted an interleaved fMRS and functional magnetic resonance imaging (fMRI) experiment using a visual stimulus with varying contrast levels. Methods: A total of 20 datasets were acquired on a 7T MRI scanner. The visual task consisted of two STIM blocks (30 s/20 s ON/OFF, 4 min), with 10% or 100% contrast, interleaved with a 5 min REST block. A dynamic fitting approach was used for fMRS data analysis. For metabolite level changes, the STIM conditions were modeled in two different ways: either considering the full STIM block as active condition (full-block model) or only modeling the ON blocks as active condition (sub-block model). For linewidth changes due to the BOLD effect, STIM conditions were modeled using the sub-block model. Results: For both models, we observed significant increases in glutamate levels for both the 10% and 100% visual contrasts, but no significant difference between the contrasts. Decreases in aspartate, and glucose, and increases in total N-acetylaspartate and total creatine were also detected, although less consistently across both 10% and 100% visual contrasts. BOLD-driven linewidth decreases and fMRI-derived BOLD increases within the MRS voxel were observed at both 10% and 100% contrasts, with larger changes at 100% compared to 10% in the fMRI-derived BOLD only. We observed a non-linear relation between visual contrast, the BOLD response, and the glutamate response. Conclusion: Our study highlights the potential of fMRS as a complementary technique to BOLD fMRI for investigating the complex interplay between visual contrast, neural activity, and neurometabolism. Future studies should further explore the temporal response profiles of different neurometabolites and refine the statistical models used for fMRS analysis.

Prefrontal Glutathione Levels in Major Depressive Disorder Are Linked to a Lack of Positive Affect.

Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders, with symptoms including persistent sadness and loss of interest. MDD is associated with neurochemical alterations in GABA, glutamate, and glutamine levels but, to date, few studies have examined changes in glutathione (GSH) in MDD. This study investigated changes in GSH in an unmedicated group of young adults, including 46 participants with current (n = 12) or past MDD (n = 34) and 20 healthy controls. Glutathione levels were assessed from GSH-edited magnetic resonance (MR) spectra, acquired from a voxel in the left prefrontal cortex, and depressive symptoms were evaluated with validated questionnaires and clinical assessments. Cortisol levels were also assessed as a marker for acute stress. Participants with current MDD demonstrated elevated GSH in comparison to participants with past MDD and controls, although the results could be influenced by differences in tissue composition within the MRS voxel. In addition, participants with both current and past MDD showed elevated cortisol levels in comparison to controls. No significant association was observed between GSH and cortisol levels, but elevated GSH levels were associated with a decrease in positive affect. These results demonstrate for the first time that elevated GSH in current but not past depression may reflect a state rather than a trait neurobiological change, related to a loss of positive affect.

Quantification of the neurochemical profile of the human putamen using STEAM MRS in a cohort of elderly subjects at 3 T and 7 T: Ruminations on the correction strategy for the tissue voxel composition.

The aim of this work is to quantify the metabolic profile of the human putamen in vivo in a cohort of elderly subjects using single-voxel proton magnetic resonance spectroscopy. To obtain metabolite concentrations specific to the putamen, we investigated a correction method previously proposed to account for the tissue composition of the volume of interest. We compared the method with the conventional approach, which a priori assumes equal metabolite concentrations in GM and WM. Finally, we compared the concentrations acquired at 3 Tesla (T) and 7 T MRI scanners. Spectra were acquired from 15 subjects (age: 67.7 ± 8.3 years) at 3 T and 7 T, using an ultra-short echo time, stimulated echo acquisition mode sequence. To robustly estimate the WM-to-GM metabolite concentration ratio, five additional subjects were measured for whom the MRS voxel was deliberately shifted from the putamen in order to increase the covered amount of surrounding WM. The concentration and WM-to-GM concentration ratio for 16 metabolites were reliably estimated. These ratios ranged from ~0.3 for γ-aminobutyric acid to ~4 for N-acetylaspartylglutamate. The investigated correction method led to significant changes in concentrations compared to the conventional method, provided that the ratio significantly differed from unity. Finally, we demonstrated that differences in tissue voxel composition cannot fully account for the observed concentration difference between field strengths. We provide not only a fully comprehensive quantification of the neurochemical profile of the putamen in elderly subjects, but also a quantification of the WM-to-GM concentration ratio. This knowledge may serve as a basis for future studies with varying tissue voxel composition, either due to tissue atrophy, inconsistent voxel positioning or simply when pooling data from different voxel locations.

New Insights into the Spread of MRS-Based Water T2 Values Observed in Highly Fatty Replaced Muscles.

The reference standard for assessing water T2 (T2,H2O ) at high fat fraction (FF) is 1 H MRS. T2,H2O (T2,H2O,MRS ) dependence on FF (FFMRS ) has recently been demonstrated in muscle at high FF (i.e. ≥60%). To investigate the relationship between T2,H2O,MRS and FFMRS in the thigh/leg muscles of patients with neuromuscular diseases and to compare with quantitative MRI. Retrospective case-control study. A total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male). A 3-T; single-voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T2 mapping, T2,H2O,MRI ), three-point Dixon imaging (for FFMRI and mapping). Mono-exponential and bi-exponential models were fitted to water T2 decay curves to extract T2,H2O,MRS and FFMRS . Water resonance full-width-at-half-maximum (FWHM) and B0 spread (∆B0 ) values were calculated. T2,H2O,MRI (mean), FFMRI (mean, kurtosis, and skewness), and (mean) values were estimated in the MRS voxel. Mann-Whitney U tests, Kruskal-Wallis tests. A P-value <0.05 was considered statistically significant. Normal T2,H2O,MRS threshold was defined as the 90th percentile in healthy controls: 30.3 msec. T2,H2O,MRS was significantly higher in all patients with FFMRS < 60% compared to healthy controls. We discovered two subgroups in patients with FFMRS ≥ 60%: one with T2,H2O,MRS ≥ 30.3 msec and one with T2,H2O,MRS < 30.3 msec including abnormally low T2,H2O,MRS . The latter subgroup had significantly higher water resonance FWHM, ∆B0 , FFMRI kurtosis, and skewness values but nonsignificantly different (P = 1.00) and long T2,H2O,MRS component and its fraction (P > 0.11) based on the bi-exponential analysis. The findings suggest that the cause for (abnormally) T2,H2O,MRS at high FFMRS is biophysical, due to differences in susceptibility between muscle and fat (increased FWHM and ∆B0 ), rather than pathophysiological such as compartmentation changes, which would be reflected by the bi-exponential analysis. 3 TECHNICAL EFFICACY: Stage 3.

J-difference GABA-edited MRS reveals altered cerebello-thalamo-cortical metabolism in patients with hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common neurological manifestation of liver cirrhosis and is characterized by an increase of ammonia in the brain accompanied by a disrupted neurotransmitter balance, including the GABAergic and glutamatergic systems. The aim of this study is to investigate metabolic abnormalities in the cerebello-thalamo-cortical system of HE patients using GABA-edited MRS and links between metabolite levels, disease severity, critical flicker frequency (CFF), motor performance scores, and blood ammonia levels. GABA-edited MRS was performed in 35 participants (16 controls, 19 HE patients) on a clinical 3T MRI system. MRS voxels were placed in the right cerebellum, left thalamus, and left motor cortex. Levels of GABA+ and of other metabolites of interest (glutamine, glutamate, myo-inositol, glutathione, total choline, total NAA, and total creatine) were assessed. Group differences in metabolite levels and associations with clinical metrics were tested. GABA+ levels were significantly increased in the cerebellum of patients with HE. GABA+ levels in the motor cortex were significantly decreased in HE patients, and correlated with the CFF (r = 0.73; p < .05) and motor performance scores (r = -0.65; p < .05). Well-established HE-typical metabolite patterns (increased glutamine, decreased myo-inositol and total choline) were confirmed in all three regions and were closely linked to clinical metrics. In summary, our findings provide further evidence for alterations in the GABAergic system in the cerebellum and motor cortex in HE. These changes were accompanied by characteristic patterns of osmolytes and oxidative stress markers in the cerebello-thalamo-cortical system. These metabolic disturbances are a likely contributor to HE motor symptoms in HE. In patients with hepatic encephalopathy, GABA+ levels in the cerebello-thalamo-cortical loop are significantly increased in the cerebellum and significantly decreased in the motor cortex. GABA+ levels in the motor cortex strongly correlate with critical flicker frequency (CFF) and motor performance score (pegboard test tPEG), but not blood ammonia levels (NH3).

TDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Background and objectiveTranscranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. MethodsData from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. ResultsIn M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = −3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. ConclusionsOur data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects.

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

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. 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. 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. 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 twosingle voxels without a significant decrease in spectral quality or metabolite quantification accuracy and thus provides a new option for multiple-voxel applications.

Neurochemical levels measured by 1H MR spectroscopy are associated with amyloid‐β and tau deposition in cognitively unimpaired older adults

AbstractBackgroundProton MR Spectroscopy (1H MRS) provides non‐invasive measurements of alterations in brain biochemistry associated with neuronal and glial abnormalities in neurodegeneration. 1H MRS with along with automated voxel placement (AVP) improves the precision of 1H MRS metabolite measurements. Our objective was to investigate the association of 1H MRS metabolites obtained by the advanced sLASER single voxel 1H MRS protocol with early tau deposition as measured by AV‐1451 PET and Aβ deposition as measured by 11C‐Pittsburgh compound B (PiB) PET in cognitively unimpaired older adults.MethodCognitively unimpaired adults with median (range) age of 77 (66, 94) from the population‐based Mayo Clinic Study of Aging (MCSA) participated in the single‐voxel 1H MRS study (n=40). All participants had an MRI, 11C‐PiB and AV‐1451 PET examinations. The posterior cingulate cortex (PCC) and the left hippocampus (LHC) were chosen for the 1H MRS voxel locations because of their vulnerability to early AD pathology. Right hippocampus was not studied due to time constraints of the MR examination. 1H MRS was performed at 3T (Siemens) using an optimized sLASER protocol with AVP. Standardized uptake value ratios (SUVR) were calculated for global cortical and regional (PCC, LHC) PiB and AV‐1451. Associations between log transformed SUVRs and the concentration of MRS‐measured metabolites (µmol/g) were assessed using age‐adjusted Pearson correlations.ResultThe median (range) global PiB SUVR was 1.42 (1.20‐2.81) and AV‐1451 SUVR was 1.20 (0.94, 1.46). In the PCC, higher AV‐1451 SUVR was associated with lower N‐acetylaspartate (NAA) (r=‐0.375; p=0.019) and glutamate (r=‐0.354; p=0.027) concentrations. Higher global PIB SUVR was associated with higher myo‐inositol in the LHC (r=0.361; p=0.039).ConclusionLower levels of NAA, a marker of neuronal health, and the neurotransmitter glutamate are associated with local tau pathology in the PCC, suggesting early neuronal dysfunction in relation to tau accumulation. The association of hippocampal myo‐inositol, a putative glial marker, with the global cortical Aβ pathology suggests that myo‐inositol elevation may be an indicator of neuroinflammatory response to Aβ related pathology.

Evidence against altered excitatory/inhibitory balance in the posteromedial cortex of young adult APOE E4 carriers: A resting state 1H-MRS study

A strategy to gain insight into early changes that may predispose people to Alzheimer's disease (AD) is to study the brains of younger cognitively healthy people that are at increased genetic risk of AD. The Apolipoprotein (APOE) E4 allele is the strongest genetic risk factor for AD, and several neuroimaging studies comparing APOE E4 carriers with non-carriers at age ∼20–30 years have detected hyperactivity (or reduced deactivation) in posteromedial cortex (PMC), a key hub of the default network (DN), which has a high susceptibility to early amyloid deposition in AD. Transgenic mouse models suggest such early network activity alterations may result from altered excitatory/inhibitory (E/I) balance, but this is yet to be examined in humans. Here we test the hypothesis that PMC fMRI hyperactivity could be underpinned by altered levels of excitatory (glutamate) and/or inhibitory (GABA) neurotransmitters in this brain region. Forty-seven participants (20 APOE E4 carriers and 27 non-carriers) aged 18–25 years underwent resting-state proton magnetic resonance spectroscopy (1H-MRS), a non-invasive neuroimaging technique to measure glutamate and GABA in vivo. Metabolites were measured in a PMC voxel of interest and in a comparison voxel in the occipital cortex (OCC). There was no difference in either glutamate or GABA between the E4 carriers and non-carriers in either MRS voxel, or in the ratio of glutamate to GABA, a measure of E/I balance. Default Bayesian t-tests revealed evidence in support of this null finding. Our findings suggest that PMC hyperactivity in APOE E4 carriers is unlikely to be associated with, or possibly may precede, alterations in local resting-state PMC neurotransmitters, thus informing our understanding of the spatio-temporal sequence of early network alterations underlying APOE E4 related AD risk.

In vivo Molecular Signatures of Cervical Spinal Cord Pathology in Degenerative Compression.

Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and −14%) and SC (+12%, +46%, and −8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (−0.376 < r < −0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = −0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.

Estimation and removal of spurious echo artifacts in single-voxel MRS using sensitivity encoding.

In localized MRS, spurious echo artifacts commonly occur when unsuppressed signal outside the volume of interest is excited and refocused. In the spectral domain, these signals often overlap with metabolite resonances and hinder accurate quantification. Because the artifacts originate from regions separate from the target MRS voxel, this work proposes that sensitivity encoding based on receive-coil sensitivity profiles may be used to separate these signal contributions. Numerical simulations were performed to explore the effect of sensitivity-encoded separation for unknown artifact regions. An imaging-based approach was developed to identify regions that may contribute to spurious echo artifacts, and tested for sensitivity-based unfolding of signal on six data sets from three brain regions. Spectral data reconstructed using the proposed method ("ERASE") were compared with the standard coil combination. The method was able to fully unfold artifact signals if regions were known a priori. Mismatch between estimated and true artifact regions reduced the efficiency of removal, yet metabolite signals were unaffected. Water suppression imaging was able to identify regions of unsuppressed signal, and ERASE (from up to eight regions) led to visible removal of artifacts relative to standard reconstruction. Fitting errors across major metabolites were also lower; for example, Cramér-Rao lower bounds of myo-inositol were 13.7% versus 17.5% for ERASE versus standard reconstruction, respectively. The ERASE reconstruction tool was demonstrated to reduce spurious echo artifacts in single-voxel MRS. This tool may be incorporated into standard workflows to improve spectral quality when hardware limitations or other factors result in out-of-voxel signal contamination.

TDCS-induced modulation of GABA concentration and dopamine release in the human brain: A combination study of magnetic resonance spectroscopy and positron emission tomography

BackgroundTranscranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) hypothetically modulates cognitive functions by facilitating or inhibiting neuronal activities chiefly in the cerebral cortex. The effect of tDCS in the deeper brain region, the basal ganglia-cortical circuit, remains unknown. ObjectiveTo investigate the interaction between γ-aminobutyric acid (GABA) concentrations and dopamine release following tDCS. MethodThis study used a randomized, placebo-controlled, double-blind, crossover design. Seventeen healthy male subjects underwent active and sham tDCS (13 min twice at an interval of 20 min) with the anode placed at the left DLPFC and the cathode at the right DLPFC, followed by examinations with [11C]-raclopride positron emission topography (PET) and GABA-magnetic resonance spectroscopy (MRS). MRS voxels were set in the left DLPFC and bilateral striata. Paired t-tests and regression analyses were performed for PET and MRS parameters. ResultsMRS data analyses showed elevations in GABA in the left striatum along with moderate reductions in the right striatum and the left DLPFC after active tDCS. PET data analyses showed that reductions in [11C]-raclopride binding potentials (increase in dopamine release) in the right striatum were inversely correlated with those in the left striatum after active tDCS. GABA reductions in the left DLPFC positively correlated with elevations in GABA in the left striatum and with increases in right striatal dopamine release and negatively correlated with increases in left striatal dopamine release. ConclusionThe present results suggest that tDCS to the DLPFC modulates dopamine-GABA functions in the basal ganglia-cortical circuit.

Assessment of magnetic resonance spectroscopy variability across metabolites and field strengths

AbstractBackgroundMagnetic Resonance Spectroscopy (MRS) is a non‐invasive technique assessing the concentration of various metabolites within the brain, both cross‐sectionally to characterize disease type and severity, and longitudinally to assess disease progression and potential treatment efficacy in the context of disease‐modifying interventions. In such context, the involvement of multiple imaging facilities inevitably introduces variability, whose amount must be known to inform on comparability between sites and sensitivity to change. Our objective is to study variability in the concentration of various brain metabolites using a dedicated MRS phantom and assess impact of field strength.Methods30 sites are being considered to participate in an on‐going clinical trial in metachromatic leukodystrophy. Site qualification mandates the scanning of a dedicated MRS phantom. 30 of these HD‐polyethylene spheres were simultaneously manufactured and filled with the same mixture of chemicals mimicking main metabolite concentrations. To date, 14 sites provided data (5 1.5T scanners and 9 3T). All sites implemented a standardized single‐voxel MRS sequence. MRS voxel was placed within the phantom and acquisition repeated 3 times. Spectra were centrally analyzed using LCModel v6.3 and quality controlled by Bioclinica. Repeat acquisitions were requested for parameter deviations, voxel positioning and/or shimming issues. Results only include passing datasets. Coefficient of Variation (CV) was calculated for NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr and Lac/Cr ratios for each site and overall. LCModel quality metrics (FHWM and S/N) were also extracted to assess spectra quality. Comparison between field strengths was carried out using t‐tests.ResultsAverage CV by site was 2.0% for NAA/Cr (2.5% at 1.5T and 1.8% at 3T), 2.4% for Cho/Cr, 3.0% for mI/Cr, 4.5% for Glx/Cr and 6.1% for Lac/Cr. CVs were generally lower at 3T (except for Lac/Cr) although difference was not significant. As expected, Signal‐to‐Noise was higher at 3T (p=0.05). Overall CV by metabolite across scanners was much higher (ranging from 4.6% for Cho/Cr up to 12.1% for Lac/Cr).ConclusionMRS measures of metabolite concentrations have low variability at scanner‐level, insensitive to field strength. Nevertheless, variability across sites is much higher and would require, if possible, cross‐calibration. These phantom data make such calibration possible and will improve sensitivity of subject data analyses.

MR spectroscopy using static higher order shimming with dynamic linear terms (HOS-DLT) for improved water suppression, interleaved MRS-fMRI, and navigator-based motion correction at 7T.

PurposeTo interleave global and local higher order shimming for single voxel MRS. Single voxel MR spectroscopy requires optimization of the B0 field homogeneity in the region of the voxel to obtain a narrow linewidth and provide high data quality. However, the optimization of local higher order fields on a localized MRS voxel typically leads to large field offsets outside that volume. This compromises interleaved MR sequence elements that benefit from global field homogeneity such as water suppression, interleaved MRS‐fMRI, and MR motion correction.MethodsA shimming algorithm was developed to optimize the MRS voxel homogeneity and the whole brain homogeneity for interleaved sequence elements, using static higher order shims and dynamic linear terms (HOS‐DLT). Shimming performance was evaluated using 6 brain regions and 10 subjects. Furthermore, the benefits of HOS‐DLT was demonstrated for water suppression, MRS‐fMRI, and motion corrected MRS using fat‐navigators.ResultsThe HOS‐DLT algorithm was shown to improve the whole brain homogeneity compared to an MRS voxel‐based shim, without compromising the MRS voxel homogeneity. Improved water suppression over the brain, reduced image distortions in MRS‐fMRI, and improved quality of motion navigators were demonstrated using the HOS‐DLT method.ConclusionHOS‐DLT shimming allowed for both local and global field homogeneity, providing excellent MR spectroscopy data quality, as well as good field homogeneity for interleaved sequence elements, even without the need for dynamic higher order shimming capabilities.

J‐difference‐edited MRS measures of γ‐aminobutyric acid before and after acute caffeine administration

The aim of this study was to investigate potential effects of acute caffeine intake on J-difference-edited MRS measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). J-difference-edited Mescher-Garwood PRESS (MEGA-PRESS) and conventional PRESS data were acquired at 3T from voxels in the anterior cingulate and occipital area of the brain in 15 healthy subjects, before and after oral intake of a 200-mg caffeine dose. MEGA-PRESS data were analyzed with the MATLAB-based Gannet tool to estimate GABA+ macromolecule (GABA+) levels, while PRESS data were analyzed with LCModel to estimate levels of glutamate, glutamate+glutamine, N-acetylaspartate, and myo-inositol. All metabolites were quantified with respect to the internal reference compounds creatine and tissue water, and compared between the pre- and post-caffeine intake condition. For both MRS voxels, mean GABA+ estimates did not differ before and after caffeine intake. Slightly lower estimates of myo-inositol were observed after caffeine intake in both voxels. N-acetylaspartate, glutamate, and glutamate+glutamine did not show significant differences between conditions. Mean GABA+ estimates from J-difference-edited MRS in two different brain regions are not altered by acute oral administration of caffeine. These findings may increase subject recruitment efficiency for MRS studies.

Neurochemical differences between bipolar disorder type I and II in superior temporal cortices: A proton magnetic resonance spectroscopy study

BackgroundDespite the diagnostic challenges in categorizing bipolar disorder subtypes, bipolar I and II disorders (BD-I and BD-II respectively) are valid indices for researchers. Subtle neurobiological differences may underlie clinical differences between mood disorder subtypes. The aims of this study were to investigate neurochemical differences between bipolar disorder subtypes. MethodsEuthymic BD-II patients (n = 21) are compared with BD-I (n = 28) and healthy comparison subjects (HCs, n = 30). Magnetic Resonance Imaging (MRI) and proton spectroscopy (1H MRS) were performed on a 3T Siemens Tim Trio system. MRS voxels were located in the left/right superior temporal cortices, and spectra acquired with the single voxel Point REsolved Spectroscopy Sequence (PRESS). The spectroscopic data were analyzed with LCModel (Version 6.3.0) software. ResultsThere were significant differences between groups in terms of glutamate [F = 6.27, p = 0.003], glutamate + glutamine [F = 6.08, p = 0.004], inositol containing compounds (Ino) (F = 9.25, p < 0.001), NAA [F = 7.63, p = 0.001] and creatine + phosphocreatine [F = 11.06, p < 0.001] in the left hemisphere and Ino [F = 5.65, p = 0.005] in the right hemisphere. Post-hoc comparisons showed that the BD-I disorder group had significantly lower metabolite levels in comparison to the BD-II and the HC groups. LimitationsThis was a cross-sectional study with a small sample size. In addition, patients were on various psychotropic medications, which may have impacted the results. ConclusionsNeurochemical levels, in the superior temporal cortices, measured with 1H-MRS discriminated between BD-II and BD-I. Although further studies are needed, one may speculate that the superior temporal cortices (particularly left hemispheric) play a critical role, whose pathology may be related to subtyping bipolar disorder.

Automated Voxel Placement: A Linux-based Suite of Tools for Accurate and Reliable Single Voxel Coregistration.

BackgroundSingle-voxel proton magnetic resonance spectroscopy (1H MRS) is a powerful technique for studying in vivo neurochemistry, but has an often-overlooked source of error variance: inconsistent voxel placement between scans. We developed and evaluated an Automated Voxel Placement (AVP) procedure for accurate and reliable 1H MRS voxel prescription. AVP is a suite of Linux-based programs that facilitate automated template-driven single-voxel coregistration.MethodsThree studies were conducted to evaluate AVP for prescription of one voxel: left dorsolateral prefrontal cortex. First, we evaluated how robust AVP was to ‘extreme’ subject head positions/angulations within the scanner head coil. Second, subjects (N = 13) were recruited and underwent MR scans. Manual voxel prescription (n = 5) was contrasted with AVP (n = 8). A subset of AVP subjects (n = 4) completed a second scan. Third, ongoing data collection (n = 16; recruited for a separate study) helped evaluate AVP. Voxel placement accuracy was quantified as 3D geometric voxel overlap percentage between each subject’s voxel and the template voxel. Reliability was quantified as 3D geometric voxel overlap percentage across subjects at each time point and within subjects who completed two scans.ResultsResults demonstrated that AVP was robust to ‘extreme’ head positions (97.5% - 97.9% overlap with the template voxel). AVP was significantly more accurate (baseline and follow-up: 96.2% ± 3.0% and 97.6% ± 1.4% overlap) than manual voxel placement (67.7% ± 22.8% overlap; ps<.05). AVP was reliable within- (97.9%) and between-subjects (94.2% and 97.2% overlap; baseline and follow-up; respectively). Finally, ongoing data collection indicates AVP is accurate (96.0%).ConclusionThese pilot studies demonstrated that AVP was feasible, accurate, and reliable method for automated single voxel coregistration.

Multimodality Neuroimaging in Mild Cognitive Impairment: A Cross-sectional Comparison Study.

Background and Purpose:Mild cognitive impairment (MCI) is a focus of considerable research. The present study aimed to test the utility of a logistic regression-derived classifier, combining specific quantitative multimodal magnetic resonance imaging (MRI) data for the early objective phenotyping of MCI in the clinic, over structural MRI data.Methods:Thirty-three participants with cognitively stable amnestic MCI; 15 MCI converters to early Alzheimer's disease (AD; diseased controls) and 20 healthy controls underwent high-resolution T1-weighted volumetric MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H MR spectroscopy). The regional volumes were obtained from T1-weighted MRI. The fractional anisotropy and mean diffusivity maps were derived from DTI over multiple white matter regions. The 1H MRS voxels were placed over posterior cingulate gyri, and N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myoinositol (mI/Cr), and NAA/mI ratios were obtained. A multimodal classifier comprising MR volumetry, DTI, and MRS was prepared. A cutoff point was arrived based on receiver operator characteristics analysis. Results were considered significant, if P < 0.05.Results:The most sensitive individual marker to discriminate MCI from controls was DTI (90.9%), with a specificity of 50%. For classifying MCI from AD, the best individual modality was DTI (72.7%), with a high specificity of 87.9%. The multimodal classifier approach for MCI control classification achieved an area under curve (AUC) (AUC = 0.89; P < 0.001), with 93.9% sensitivity and 70% specificity. The combined classifier for MCI-AD achieved a highest AUC (AUC = 0.93; P < 0.001), with 93% sensitivity and 85.6% specificity.Conclusions:The combined method of gray matter atrophy, white matter tract changes, and metabolite variation achieved a better performance at classifying MCI compared to the application of individual MRI biomarkers.