Submillimeter fMRI Acquisition Techniques for Detection of Laminar and Columnar Level Brain Activation.

Since the first demonstration in the early 1990s, functional MRI (fMRI) has emerged as one of the most powerful, noninvasive neuroimaging tools to probe brain functions. Subsequently, fMRI techniques have advanced remarkably, enabling the acquisition of functional signals with a submillimeter voxel size. This innovation has opened the possibility of investigating subcortical neural activities with respect to the cortical depths or cortical columns. For this purpose, numerous previous works have endeavored to design suitable functional contrast mechanisms and dedicated imaging techniques. Depending on the choice of the functional contrast, functional signals can be detected with high sensitivity or with improved spatial specificity to the actual activation site, and the pertaining issues have been discussed in a number of earlier works. This review paper primarily aims to provide an overview of the subcortical fMRI techniques that allow the acquisition of functional signals with a submillimeter resolution. Here, the advantages and disadvantages of the imaging techniques will be described and compared. We also summarize supplementary imaging techniques that assist in the analysis of the subcortical brain activation for more accurate mapping with reduced geometric deformation. This review suggests that there is no single universally accepted method as the gold standard for subcortical fMRI. Instead, the functional contrast and the corresponding readout imaging technique should be carefully determined depending on the purpose of the study. Due to the technical limitations of current fMRI techniques, most subcortical fMRI studies have only targeted partial brain regions. As a future prospect, the spatiotemporal resolution of fMRI will be pushed to satisfy the community's need for a deeper understanding of whole-brain functions and the underlying connectivity in order to achieve the ultimate goal of a time-resolved and layer-specific spatial scale. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

How brain networks tic: Predicting tic severity through rs-fMRI dynamics in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and phonic tics, which several different theories, such as basal ganglia-thalamo-cortical loop dysfunction and amygdala hypersensitivity, have sought to explain. Previous research has shown dynamic changes in the brain prior to tic onset leading to tics, and this study aims to investigate the contribution of network dynamics to them. For this, we have employed three methods of functional connectivity to resting-state fMRI data - namely the static, the sliding window dynamic and the ICA based estimated dynamic; followed by an examination of the static and dynamic network topological properties. A leave-one-out (LOO-) validated regression model with LASSO regularization was used to identify the key predictors. The relevant predictors pointed to dysfunction of the primary motor cortex, the prefrontal-basal ganglia loop and amygdala-mediated visual social processing network. This is in line with a recently proposed social decision-making dysfunction hypothesis, opening new horizons in understanding tic pathophysiology.

Visuo-spatial processing is linked to cortical glutamate dynamics in Parkinson's disease - a 7-T functional magnetic resonance spectroscopy study.

BACKGROUND AND PURPOSE: Cognitive decline is a frequent and debilitating non-motor symptom for patients with Parkinson's disease (PD). Metabolic alterations in the occipital cortex during visual processing may serve as a biomarker for cognitive decline in patients with PD. METHODS: Sixteen patients with PD (Unified Parkinson's Disease Rating Scale Part 3, OFF, 38.69 ± 17.25) and 10 age- and sex-matched healthy controls (HC) underwent 7-T functional magnetic resonance spectroscopy (MRS) utilizing a visual checkerboard stimulation. Glutamate metabolite levels during rest versus stimulation were compared. Furthermore, correlates of the functional MRS response with performance in visuo-cognitive tests were investigated. RESULTS: No differences in static MRS between patients with PD and HC were detected, but a dynamic glutamate response was observed in functional MRS in HC upon visual stimulation, which was blunted in patients with PD (F1,22 = 7.13, p = 0.014; η p 2 = 0.245). A diminished glutamate response correlated with poorer performance in the Benton Judgment of Line Orientation test in PD (r = -0.57, p = 0.020). CONCLUSIONS: Our results indicate that functional MRS captures even subtle differences in neural processing linked to the behavioral performance, which would have been missed by conventional, static MRS. Functional MRS thus represents a promising tool for studying molecular alterations at high sensitivity. Its prognostic potential should be evaluated in longitudinal studies, prospectively contributing to earlier diagnosis and individual treatment decisions.

Germany's journey toward 14 Tesla human magnetic resonance.

Multiple sites within Germany operate human MRI systems with magnetic fields either at 7 Tesla or 9.4 Tesla. In 2013, these sites formed a network to facilitate and harmonize the research being conducted at the different sites and make this technology available to a larger community of researchers and clinicians not only within Germany, but also worldwide. The German Ultrahigh Field Imaging (GUFI) network has defined a strategic goal to establish a 14 Tesla whole-body human MRI system as a national research resource in Germany as the next progression in magnetic field strength. This paper summarizes the history of this initiative, the current status, the motivation for pursuing MR imaging and spectroscopy at such a high magnetic field strength, and the technical and funding challenges involved. It focuses on the scientific and science policy process from the perspective in Germany, and is not intended to be a comprehensive systematic review of the benefits and technical challenges of higher field strengths.

A novel MRI-based quantitative water content atlas of the human brain.

The measurement of quantitative, tissue-specific MR properties, e.g., water content, longitudinal relaxation time (T1) and effective transverse relaxation time (T2⁎), using quantitative MRI at a clinical field strength (1.5 T to 3T) is a well-explored topic. However, none of the commonly used standard brain atlases, such as MNI or JHU, provide quantitative information. Within the framework of quantitative MRI of the brain, this work reports on the development of the first quantitative brain atlas for tissue water content at 3T. A methodology to create this quantitative atlas of in vivo brain water content based on healthy volunteers is presented, and preliminary, practical examples of its potential applications are also shown. Established methods for the fast and reliable measurement of the absolute water content were used to achieve high precision and accuracy. Water content and T2⁎ were mapped based on two different methods: an intermediate-TR, two-point method and a long-TR, single-scan method. Twenty healthy subjects (age 25.3 ± 2.5 years) were examined with these quantitative imaging protocols. The images were normalised to MNI stereotactic coordinates, and water content atlases of healthy volunteers were created for each method and compared. Regions-of-interest were generated with the help of a standard MNI template, and water content values averaged across the ROIs were compared to water content values from the literature. Finally, in order to demonstrate the strength of quantitative MRI, water content maps from patients with pathological changes in the brain due to stroke, tumour (glioblastoma) and multiple sclerosis were voxel-wise compared to the healthy brain. The water content atlases were largely independent of the method used to acquire the individual water maps. Global grey matter and white matter water content values between the methods agreed with each other to within 0.5 %. The feasibility of detecting abnormal water content in the brains of patients based on comparison to a healthy brain water content atlas was demonstrated. In summary, the first quantitative water content brain atlas in vivo has been developed, and a voxel-wise assessment of pathology-related changes in the brain water content has been performed. These results suggest that qMRI, in combination with a water content atlas, allows for a quantitative interpretation of changes due to disease and could be used for disease monitoring.

Mapping of whole-cerebrum resting-state networks using ultra-high resolution acquisition protocols.

Resting-state functional magnetic resonance imaging (fMRI) has been used in numerous studies to map networks in the brain that employ spatially disparate regions. However, attempts to map networks with high spatial resolution have been hampered by conflicting technical demands and associated problems. Results from recent fMRI studies have shown that spatial resolution remains around 0.7 × 0.7 × 0.7 mm3 , with only partial brain coverage. Therefore, this work aims to present a novel fMRI technique that was developed based on echo-planar-imaging with keyhole (EPIK) combined with repetition-time-external (TR-external) EPI phase correction. Each technique has been previously shown to be effective in enhancing the spatial resolution of fMRI, and in this work, the combination of the two techniques into TR-external EPIK provided a nominal spatial resolution of 0.51 × 0.51 × 1.00 mm3 (0.26 mm3 voxel) with whole-cerebrum coverage. Here, the feasibility of using half-millimetre in-plane TR-external EPIK for resting-state fMRI was validated using 13 healthy subjects and the corresponding reproducible mapping of resting-state networks was demonstrated. Furthermore, TR-external EPIK enabled the identification of various resting-state networks distributed throughout the brain from a single fMRI session, with mapping fidelity onto the grey matter at 7T. The high-resolution functional image further revealed mesoscale anatomical structures, such as small cerebral vessels and the internal granular layer of the cortex within the postcentral gyrus.

mGluR5 and GABAA receptor-specific parametric PET atlas construction-PET/MR data processing pipeline, validation, and application.

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR5 and GABAA are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non-displaceable binding potential (BPND ), and total distribution volume (VT ) based on simultaneously acquired bolus-infusion positron emission tomography (PET) and MR data. The pipeline was applied to [11 C]ABP688-PET/MR (13 healthy male non-smokers, 26.6 ± 7.0 years) and [11 C]Flumazenil-PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as VT and BPND atlases of mGluR5 and GABAA , were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δABP  = 3.0 ± 1.0% and δFMZ  = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σABP  = 4.0%-16.0%, σFMZ  = 3.9%-9.5%). An evaluation of PET-to-PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [15 O]H2 O-template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions.

Primary Multiparametric Quantitative Brain MRI: State-of-the-Art Relaxometric and Proton Density Mapping Techniques.

This review on brain multiparametric quantitative MRI (MP-qMRI) focuses on the primary subset of quantitative MRI (qMRI) parameters that represent the mobile ("free") and bound ("motion-restricted") proton pools. Such primary parameters are the proton densities, relaxation times, and magnetization transfer parameters. Diffusion qMRI is also included because of its wide implementation in complete clinical MP-qMRI application. MP-qMRI advances were reviewed over the past 2 decades, with substantial progress observed toward accelerating image acquisition and increasing mapping accuracy. Areas that need further investigation and refinement are identified as follows: (a) the biologic underpinnings of qMRI parameter values and their changes with age and/or disease and (b) the theoretical limitations implicitly built into most qMRI mapping algorithms that do not distinguish between the different spatial scales of voxels versus spin packets, the central physical object of the Bloch theory. With rapidly improving image processing techniques and continuous advances in computer hardware, MP-qMRI has the potential for implementation in a wide range of clinical applications. Currently, three emerging MP-qMRI applications are synthetic MRI, macrostructural qMRI, and microstructural tissue modeling.

Development of a novel 10-echo multi-contrast sequence based on EPIK to deliver simultaneous quantification of T2 and T2* with application to oxygen extraction fraction.

PURPOSE: The simultaneous quantification of T2 and T2 * maps based on fast sequences for combined GE and SE acquisition has rekindled research and clinical interest by offering a wide range of attractive applications, e.g., dynamic tracking of oxygen extraction fraction (OEF). However, previously published methods based on EPI-readouts have been hindered by resolution and the number of acquired echoes. METHODS: This work presents a novel 10-echo GE-SE EPIK (EPI with keyhole) sequence for the rapid quantification of T2 '. T2 /T2 * maps from the GE-SE EPIK sequence were validated using three phantoms and 15 volunteers at 3T. The incorporation of a sliding window approach, combined with the full sampling of the k-space center inherent to EPIK, enables a high effective temporal resolution. That is, for an eight-slice breath-hold experiment, a temporal sampling rate of eight reconstructed slices per 1.1 s. RESULTS: In comparison with repeated single-echo SE, multi-echo GE, and spectroscopy methods, the GE-SE EPIK sequence shows good agreement in quantifying T2 /T2 * values, while the gray matter/white matter separation yielded the expected contrast differentiation. The OEF was calculated with a view to an initial application with clinical relevance, producing results comparable to those in the literature and with good sensitivity in breath-hold experiments. CONCLUSIONS: GE-SE EPIK provides increased resolution and more echoes, including two SEs, than comparable sequences. Moreover, GE-SE EPIK achieves this within an acquisition time of 57 s for 20 slices (matrix size = 128×128; FOV = 24 cm) and with a reasonably short TE for the final echo (114 ms). The sequence can dynamically track OEF changes in a breath-hold experiment.

Whole-Brain Water Content Mapping Using Super-Resolution Reconstruction with MRI Acquisition in 3 Orthogonal Orientations.

PURPOSE: Brain water content provides rich tissue contrast comparable to that of longitudinal relaxation time T1 , but mapping is usually performed at modest resolution. In particular, the slice thickness in 2D mapping methods is limited. Here, we combine super-resolution reconstruction techniques with a fast water content mapping method to acquire high and isotropic resolution (0.75 mm) water content maps at 3 Tesla. METHODS: A high-resolution multi-echo gradient echo image is super-resolution-reconstructed from 3 low-resolution, orthogonal multi-echo gradient echo image acquisitions, followed by water content mapping. The mapping accuracy and SNR of the proposed method are assessed using numerical simulations, phantom studies, and in vivo data acquired from 6 healthy volunteers at 3 Tesla. A high-resolution acquisition with an established mapping method is used as a reference. RESULTS: Whole-brain water content maps with 0.75 mm isotropic resolution are demonstrated. No bias in the water content values was seen following super-resolution reconstruction. In the in vivo experiments, a lower SD of the mean water content values was observed with the proposed method compared to the reference method. CONCLUSIONS: Super-resolution reconstruction of multi-echo gradient echo data is demonstrated, enabling whole-brain water content mapping with high and isotropic resolution. The accuracy of the proposed method is shown using phantoms and 6 healthy volunteers and was found to be unchanged compared to the conventional acquisition. The proposed method could increase the sensitivity of water content mapping sufficiently to enable the detection of very small lesions, such as cortical lesions in multiple sclerosis.

Suppressing motion artefacts in MRI using an Inception-ResNet network with motion simulation augmentation.

The suppression of motion artefacts from MR images is a challenging task. The purpose of this paper was to develop a standalone novel technique to suppress motion artefacts in MR images using a data-driven deep learning approach. A simulation framework was developed to generate motion-corrupted images from motion-free images using randomly generated motion profiles. An Inception-ResNet deep learning network architecture was used as the encoder and was augmented with a stack of convolution and upsampling layers to form an encoder-decoder network. The network was trained on simulated motion-corrupted images to identify and suppress those artefacts attributable to motion. The network was validated on unseen simulated datasets and real-world experimental motion-corrupted in vivo brain datasets. The trained network was able to suppress the motion artefacts in the reconstructed images, and the mean structural similarity (SSIM) increased from 0.9058 to 0.9338. The network was also able to suppress the motion artefacts from the real-world experimental dataset, and the mean SSIM increased from 0.8671 to 0.9145. The motion correction of the experimental datasets demonstrated the effectiveness of the motion simulation generation process. The proposed method successfully removed motion artefacts and outperformed an iterative entropy minimization method in terms of the SSIM index and normalized root mean squared error, which were 5-10% better for the proposed method. In conclusion, a novel, data-driven motion correction technique has been developed that can suppress motion artefacts from motion-corrupted MR images. The proposed technique is a standalone, post-processing method that does not interfere with data acquisition or reconstruction parameters, thus making it suitable for routine clinical practice.

Compressed Sensing in Sodium Magnetic Resonance Imaging: Techniques, Applications, and Future Prospects.

Sodium (23 Na) yields the second strongest nuclear magnetic resonance (NMR) signal in biological tissues and plays a vital role in cell physiology. Sodium magnetic resonance imaging (MRI) can provide insights into cell integrity and tissue viability relative to pathologies without significant anatomical alternations, and thus it is considered to be a potential surrogate biomarker that provides complementary information for standard hydrogen (1 H) MRI in a noninvasive and quantitative manner. However, sodium MRI suffers from a relatively low signal-to-noise ratio and long acquisition times due to its relatively low NMR sensitivity. Compressed sensing-based (CS-based) methods have been shown to accelerate sodium imaging and/or improve sodium image quality significantly. In this manuscript, the basic concepts of CS and how CS might be applied to improve sodium MRI are described, and the historical milestones of CS-based sodium MRI are briefly presented. Representative advanced techniques and evaluation methods are discussed in detail, followed by an expose of clinical applications in multiple anatomical regions and diseases as well as thoughts and suggestions on potential future research prospects of CS in sodium MRI. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Microglial activation and blood-brain barrier permeability in cerebral small vessel disease.

Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying pathogenesis is poorly understood, but both neuroinflammation and increased blood-brain barrier permeability have been hypothesized to play a role, and preclinical studies suggest the two processes may be linked. We used PET magnetic resonance to simultaneously measure microglial activation using the translocator protein radioligand 11C-PK11195, and blood-brain barrier permeability using dynamic contrast enhanced MRI. A case control design was used with two disease groups with sporadic SVD (n = 20), monogenic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL), and normal controls (n = 20) were studied. Hotspots of increased glial activation and blood-brain barrier permeability were identified as values greater than the 95th percentile of the distribution in controls. In sporadic SVD there was an increase in the volume of hotspots of both 11C-PK11195 binding (P = 0.003) and blood-brain barrier permeability (P = 0.007) in the normal appearing white matter, in addition to increased mean blood-brain barrier permeability (P < 0.001). In CADASIL no increase in blood-brain barrier permeability was detected; there was a non-significant trend to increased 11C-PK11195 binding (P = 0.073). Hotspots of 11C-PK11195 binding and blood-brain barrier permeability were not spatially related. A panel of 93 blood biomarkers relating to cardiovascular disease, inflammation and endothelial activation were measured in each participant; principal component analysis was performed and the first component related to blood-brain barrier permeability and microglial activation. Within the sporadic SVD group both hotspot and mean volume blood-brain barrier permeability values in the normal appearing white matter were associated with dimension 1 (ß = 0.829, P = 0.017, and ß = 0.976, P = 0.003, respectively). There was no association with 11C-PK11195 binding. No associations with blood markers were found in the CADASIL group. In conclusion, in sporadic SVD both microglial activation and increased blood-brain barrier permeability occur, but these are spatially distinct processes. No evidence of increased blood-brain barrier permeability was found in CADASIL.

A software-based approach for calculating spatially resolved radiation exposure for structural radiation protection in nuclear medical imaging.

The objective of the work described is the development of a software tool to provide the calculation routines for structural radiation protection from positron and gamma emitters, for example,18F. The calculation of the generated local annual dose in the vicinity of these radioactive sources supports the engineering of structural measures necessary to meet regulatory guidelines. In addition to accuracy and precision, a visual and intuitive presentation of the calculation results enables fast evaluation. Finally, the calculated results are presented in a contour plot for design, evaluation, and documentation purposes. A python program was used to provide the calculation routines for structural radiation protection. For simplicity, the radiating sources can be considered as point sources. The attenuation of structural elements can be specified or, in the case of lead, calculated by virtue of its thickness. The calculated attenuation for the lead shielding is always slightly underestimated, which leads to a marginally higher calculated local dose rate than would be physically present. With the conservatively determined value, the structural radiation protection can be optimised in accordance with the general rule of as low as reasonably achievable. The pointwise comparison between the software results and the standard procedure for calculating the dose of points in space leads to similar values. In comparison with the general approach of calculating single representative points in the radiation protection area, the visual and intuitive presentation of the results supports the design and documentation of the measures required for structural radiation protection. In the present version of the software, the local dose rate and local annual dose are overestimated by a maximum of 4.5% in the case of lead shields. The proposed software, termed RadSoft, was successfully used to develop the structural radiation protection of a controlled area for hybrid magnetic resonance - positron emission tomography imaging, with the focus herein being on the requirements for PET.

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.

BACKGROUND AND PURPOSE: The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. METHODS: Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. RESULTS: The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. CONCLUSIONS: Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.

Perfusion weighted imaging using combined gradient/spin echo EPIK: Brain tumour applications in hybrid MR-PET.

Advanced perfusion-weighted imaging (PWI) methods that combine gradient echo (GE) and spin echo (SE) data are important tools for the study of brain tumours. In PWI, single-shot, EPI-based methods have been widely used due to their relatively high imaging speed. However, when used with increasing spatial resolution, single-shot EPI methods often show limitations in whole-brain coverage for multi-contrast applications. To overcome this limitation, this work employs a new version of EPI with keyhole (EPIK) to provide five echoes: two with GEs, two with mixed GESE and one with SE; the sequence is termed "GESE-EPIK." The performance of GESE-EPIK is evaluated against its nearest relative, EPI, in terms of the temporal signal-to-noise ratio (tSNR). Here, data from brain tumour patients were acquired using a hybrid 3T MR-BrainPET scanner. GESE-EPIK resulted in reduced susceptibility artefacts, shorter TEs for the five echoes and increased brain coverage when compared to EPI. Moreover, compared to EPI, EPIK achieved a comparable tSNR for the first and second echoes and significantly higher tSNR for other echoes. A new method to obtain multi-echo GE and SE data with shorter TEs and increased brain coverage is demonstrated. As proposed here, the workflow can be shortened and the integration of multimodal clinical MR-PET studies can be facilitated.

Magnetic resonance spectroscopy with transcranial direct current stimulation to explore the underlying biochemical and physiological mechanism of the human brain: A systematic review.

A large body of molecular and neurophysiological evidence connects synaptic plasticity to specific functions and energy metabolism in particular areas of the brain. Furthermore, altered plasticity and energy regulation has been associated with a number of neuropsychiatric disorders. A favourable approach enabling the modulation of neuronal excitability and energy in humans is to stimulate the brain using transcranial direct current stimulation (tDCS) and then to observe the effect on neurometabolites using magnetic resonance spectroscopy (MRS). In this way, a well-defined modulation of brain energy and excitability can be achieved using a dedicated tDCS protocol to a predetermined brain region. This systematic review was guided by the preferred reporting items for systematic reviews and meta-analysis and summarises recent literature studying the effect of tDCS on neurometabolites in the human brain as measured by proton or phosphorus MRS. Limitations and recommendations are discussed for future research. The findings of this review provide clear evidence for the potential of using tDCS and MRS to examine and understand the effect of neurometabolites in the in vivo human brain.

Comparison of EEG microstates with resting state fMRI and FDG-PET measures in the default mode network via simultaneously recorded trimodal (PET/MR/EEG) data.

Simultaneous trimodal positron emission tomography/magnetic resonance imaging/electroencephalography (PET/MRI/EEG) resting state (rs) brain data were acquired from 10 healthy male volunteers. The rs-functional MRI (fMRI) metrics, such as regional homogeneity (ReHo), degree centrality (DC) and fractional amplitude of low-frequency fluctuations (fALFFs), as well as 2-[18F]fluoro-2-desoxy-d-glucose (FDG)-PET standardised uptake value (SUV), were calculated and the measures were extracted from the default mode network (DMN) regions of the brain. Similarly, four microstates for each subject, showing the diverse functional states of the whole brain via topographical variations due to global field power (GFP), were estimated from artefact-corrected EEG signals. In this exploratory analysis, the GFP of microstates was nonparametrically compared to rs-fMRI metrics and FDG-PET SUV measured in the DMN of the brain. The rs-fMRI metrics (ReHO, fALFF) and FDG-PET SUV did not show any significant correlations with any of the microstates. The DC metric showed a significant positive correlation with microstate C (rs  = 0.73, p = .01). FDG-PET SUVs indicate a trend for a negative correlation with microstates A, B and C. The positive correlation of microstate C with DC metrics suggests a functional relationship between cortical hubs in the frontal and occipital lobes. The results of this study suggest further exploration of this method in a larger sample and in patients with neuropsychiatric disorders. The aim of this exploratory pilot study is to lay the foundation for the development of such multimodal measures to be applied as biomarkers for diagnosis, disease staging, treatment response and monitoring of neuropsychiatric disorders.

Efficient eddy current characterization using a 2D image-based sampling scheme and a model-based fitting approach.

PURPOSE: To propose two innovations to existing eddy current characterization techniques, which include (1) an efficient spatio-temporal sampling scheme and (2) a model-based fitting of spherical harmonic eddy current components. THEORY AND METHODS: This work introduces a three-plane 2D image-based acquisition scheme to efficiently sample eddy current fields. Additionally, a model-based spherical harmonic decomposition is presented, which reduces fitting noise using a rank minimization to impose an exponential decay on the eddy current amplitude evolution. Both techniques are applied in combination and analyzed in simulations for their applicability in reconstructing suitable pre-emphasis parameters. In a proof-of-concept measurement, the routine is tested for its propriety to correctly quantify user-defined field dynamics. Furthermore, based on acquired precompensation and postcompensation eddy current data, the suitability of pre-emphasis parameters calculated based on the proposed technique is evaluated. RESULTS: Simulation results derived from 500 data sets demonstrate the applicability of the acquisition scheme for the spatio-temporal sampling of eddy current fields. Compared with a conventional data processing strategy, the proposed model-based approach yields pre-emphasis parameters that reduce the average maximum residual field offset within a 10-cm-diameter spherical volume from 3.17 Hz to 0.58 Hz. Experimental data prove the proposed routine to be suitable to measure and effectively compensate for eddy currents within 10 minutes of acquisition time. CONCLUSION: The proposed framework was found to be well-suited to efficiently characterize and compensate for eddy current fields in a one-time calibration effort. It can be applied to facilitate pre-emphasis implementations, such as for dynamic B0 shimming applications.

Putaminal y-Aminobutyric Acid Modulates Motor Response to Dopaminergic Therapy in Parkinson's Disease.

BACKGROUND: Motor response to dopaminergic therapy is a characteristic of patients with Parkinson's disease (PD). Whether nondopaminergic neurotransmitters contribute to treatment response is uncertain. OBJECTIVES: The aim of this study is to determine whether putaminal y-aminobutyric acid (GABA) levels are associated with dopaminergic motor response. METHODS: We assessed putaminal GABA levels in 19 PD patients and 13 healthy controls (HCs) utilizing ultra-high field proton magnetic resonance spectroscopy. Motor performance was evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Part III, in the ON and OFF states. Statistical analysis comprised group comparisons, correlation analysis, and multiple linear regression. RESULTS: In PD, GABA levels were significantly higher compared to HCs (1.50 ± 0.26 mM vs. 1.26 ± 0.31 mM, P = 0.022). Furthermore, GABA levels were independent predictors of absolute and relative dopaminergic treatment response. CONCLUSIONS: Our findings indicate that elevated putaminal GABA levels are associated with worse dopaminergic response in PD, emphasizing the essential role of nondopaminergic neurotransmitters in motor response. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.