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ObjectiveQuantitative values derived from PET brain images are of high interest for neuroscientific applications. Insufficient DT correction (DTC) can lead to a systematic bias of the output parameters obtained by a detailed analysis of the time activity curves (TACs). The DTC method currently used for the Siemens 3T MR BrainPET insert is global, i.e., differences in DT losses between detector blocks are not considered, leading to inaccurate DTC and, consequently, to inaccurate measurements masked by a bias. However, following careful evaluation with phantom measurements, a new block-pairwise DTC method has demonstrated a higher degree of accuracy compared to the global DTC method.ApproachDifferences between the global and the block-pairwise DTC method were studied in this work by applying several radioactive tracers. We evaluated the impact on [11C]ABP688, O-(2-[18F]fluoroethyl)-L-tyrosine (FET), and [15O]H2O TACs.ResultsFor [11C]ABP688, a relevant bias of between -0.0034 and -0.0053 ml/ (cm3 • min) was found in all studied brain regions for the volume of distribution (VT) when using the current global DTC method. For [18F]FET-PET, differences of up to 10% were observed in the tumor-to-brain ratio (TBRmax), these differences depend on the radial distance of the maximum from the PET isocenter. For [15O]H2O, differences between +4% and -7% were observed in the GM region. Average biases of -4.58%, -3.2%, and -1.2% for the regional cerebral blood flow (CBF (K1)), the rate constant k2, and the volume of distribution VT were observed, respectively. Conversely, in the white matter region, average biases of -4.9%, -7.0%, and 3.8% were observed for CBF (K1), k2, and VT, respectively.ConclusionThe bias introduced by the global DTC method leads to an overestimation in the studied quantitative parameters for all applications compared to the block-pairwise method.SignificanceThe observed differences between the two DTC methods are particularly relevant for research applications in neuroscientific studies as they affect the accuracy of quantitative Brain PET images.

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.

Measurement(s) brain activity Technology Type(s) functional magnetic resonance imaging • FDG-Positron Emission Tomography Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14977851

Iterative image reconstruction is widely used in positron emission tomography. However, it is known to contribute to quantitation bias and is particularly pronounced during dynamic studies with 11C-labeled radiotracers where count rates become low towards the end of the acquisition. As the strength of the quantitation bias depends on the counts in the reconstructed frame, it can differ from frame to frame of the acquisition. This is especially relevant in the case of neuro-receptor studies with simultaneous PET/MR when a bolus-infusion protocol is applied to allow the comparison of pre- and post-task effects. Here, count dependent changes in quantitation bias may interfere with task changes. We evaluated the impact of different framing schemes on quantitation bias and its propagation into binding potential (BP) using a phantom decay study with 11C and 3D OP-OSEM. Further, we propose a framing scheme that keeps the true counts per frame constant over the acquisition time as constant framing schemes and conventional increasing framing schemes are unlikely to achieve stable bias values during the acquisition time range. For a constant framing scheme with 5 minutes frames, the BP bias was 7.13±2.01% (10.8% to 3.8%) compared to 5.63±2.85% (7.8% to 4.0%) for conventional increasing framing schemes. Using the proposed constant true counts framing scheme, a stabilization of the BP bias was achieved at 2.56±3.92% (3.5% to 1.7%). The change in BP bias was further studied by evaluating the linear slope during the acquisition time interval. The lowest slope values were observed in the constant true counts framing scheme. The constant true counts framing scheme was effective for BP bias stabilization at relevant activity and time ranges. The mean BP bias under these conditions was 2.56±3.92%, which represents the lower limit for the detection of changes in BP during equilibrium and is especially important in the case of cognitive tasks where the expected changes are low.

The suppression of distracting information in order to focus on an actual cognitive goal is a key feature of executive functions. The use of brain imaging methods to investigate the underlying neurobiological brain activations that occur during conflict processing have demonstrated a strong involvement of the fronto-parietal attention network (FPAN). Surprisingly, the directional interconnections, their time courses and activations at different frequency bands remain to be elucidated, and thus, this constitutes the focus of this study. The shared information flow between brain areas of the FPAN is provided for frequency bands ranging from the theta to the lower gamma band (4-40 Hz). We employed an adaptation of the Simon task utilizing Magnetoencephalography (MEG). Granger causality was applied to investigate interconnections between the active brain regions, as well as their directionality. Following stimulus onset, the middle frontal precentral cortex and superior parietal cortex were significantly activated during conflict processing in a time window of between 300 to 600ms. Important differences in causality were found across frequency bands between processing of conflicting stimuli in the left as compared to the right visual hemifield. The exchange of information from and to the FPAN was most prominent in the beta band. Moreover, the anterior cingulate cortex and the anterior insula represented key areas for conflict monitoring, either by receiving input from other areas of the FPAN or by generating output themselves. This indicates that the salience network is at least partly involved in processing conflict information. The present study provides detailed insights into the underlying neural mechanisms of the FPAN, especially regarding its temporal characteristics and directional interconnections.

Alterations in the substantia nigra are strongly associated with Parkinson's disease. However, due to low contrast and partial volume effects present in typical MRI images, the substantia nigra is not of sufficient size to obtain a reliable segmentation for region-of-interest based analysis. To combat this problem, the approach proposed here offers a method to investigate and reveal changes in quantitative MRI parameters in the vicinity of substantia nigra without any a priori delineation. This approach uses an alternative method of statistical, voxel-based analysis of quantitative maps and was tested on 18 patients and 15 healthy controls using a well-established, quantitative free water mapping protocol. It was possible to reveal the topology and the location of pathological changes in the substantia nigra and its vicinity. Moreover, a decrease in free water content, T1 and T2* in the vicinity of substantia nigra was indicated in the Parkinson's disease patients compared to the healthy controls. These findings reflect a disruption of grey matter and iron accumulation, which is known to lead to neurodegeneration. Consequently, the proposed method demonstrates an increased sensitivity for the detection of pathological changes-even in small regions-and can facilitate disease monitoring via quantitative MR parameters.

The default mode network (DMN), the salience network (SN), and the central executive network (CEN) are considered as the core resting-state brain networks (RSN) due to their involvement in a wide range of cognitive tasks. Despite the large body of knowledge related to their regional spontaneous activity (RSA) and functional connectivity (FC) of these networks, less is known about the dynamics of the task-associated modulation on these parameters and the task-induced interaction between these three networks. We have investigated the effects of the visual-oddball paradigm on three fMRI measures (amplitude of low-frequency fluctuations for RSA, regional homogeneity for local FC, and degree centrality for global FC) in these three core RSN. A rest-task-rest paradigm was used and the RSNs were identified using independent component analysis (ICA) on the resting-state data. The observed patterns of change differed noticeably between the networks and were tightly associated with the task-related brain activity and the distinct involvement of the networks in the performance of the single subtasks. Furthermore, the inter-network analysis showed an increased synchronization of CEN with the DMN and the SN immediately after the task, but not between the DMN and SN. Higher pre-task inter-network synchronization between the DMN and the CEN was associated with shorter reaction times and thus better performance. Our results provide some additional insights into the dynamics within and between the triple RSN. Further investigations are required in order to understand better their functional importance and interplay.

Modern magnetic resonance imaging systems are equipped with a large number of receive connectors in order to optimally support a large field-of-view and/or high acceleration in parallel imaging using high-channel count, phased array coils. Given that the MR system is equipped with a limited number of digitizing receivers and in order to support operation of multinuclear coil arrays, these connectors need to be flexibly routed to the receiver outside the RF shielded examination room. However, for a number of practical, economic and safety reasons, it is better to only route a subset of the connectors. This is usually accomplished with the use of switch matrices. These exist in a variety of topologies and differ in routing flexibility and technological implementation. A highly flexible implementation is a crossbar topology that allows to any one input to be routed to any one output and can use single PIN diodes as active elements. However, in this configuration, long open-ended transmission lines can potentially remain connected to the signal path leading to high transmission losses. Thus, especially for high-field systems compensation mechanisms are required to remove the effects of open-ended transmission line stubs. The selection of a limited number of lumped element reactance values to compensate for the for the effect of transmission line stubs in large-scale switch matrices capable of supporting multi-nuclear operation is non-trivial and is a combinatorial problem of high order. Here, we demonstrate the use of metaheuristic approaches to optimize the circuit design of these matrices that additionally carry out the optimization of distances between the parallel transmission lines. For a matrix with 128 inputs and 64 outputs a realization is proposed that displays a worst-case insertion loss of 3.8 dB.

This study aims to integrate an ultra-high-strength gradient coil system on a clinical 3 T magnet and demonstrate its preclinical imaging capabilities. Dedicated phantoms were used to qualitatively and quantitatively assess the performance of the gradient system. Advanced MR imaging sequences, including diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM), were implemented and executed on an ex vivo specimen as well as in vivo rats. The DTI and QSM results on the phantom agreed well with those in the literature. Furthermore, studies on ex vivo specimens have demonstrated the applicability of DTI and QSM on our system to probe microstructural changes in a mild traumatic brain injury rat model. The feasibility of in vivo rat DTI was also demonstrated. We showed that the inserted ultra-high-strength gradient coil was successfully integrated on a clinically used magnet. After careful tuning and calibration, we verified the accuracy and quantitative preclinical imaging capability of the integrated system in phantom and in vivo rat brain experiments. This study can be essential to establish dedicated animal MRI platform on clinical MRI scanners and facilitate translational studies at clinical settings.

ObjectivesTo apply the MB (multiband) excitation and blipped-CAIPI (blipped-controlled aliasing in parallel imaging) techniques in a spin and gradient-echo (SAGE) EPI sequence to improve the slice coverage for vessel architecture imaging (VAI).Materials and methodsBoth MB excitation and blipped-CAIPI with in-plane parallel imaging were incorporated into a gradient-echo (GE)/spin-echo (SE) EPI sequence for simultaneous tracking of the dynamic MR signal changes in both GE and SE contrasts after the injection of contrast agent. MB and singleband (SB) excitation were compared using a 20-channel head coil at 3 Tesla, and high-resolution MB VAI could be performed in 32 glioma patients.ResultsWhole-brain covered high resolution VAI can be achieved after applying multiband excitation with a factor of 2 and in-plane parallel imaging with a factor of 3. The quality of the images resulting from MB acceleration was comparable to those from the SB method: images were reconstructed without any loss of spatial resolution or severe distortions. In addition, MB and SB signal-to-noise ratios (SNR) were similar. A relative low g-factor induced from the MB acceleration method was achieved after using a blipped-CAIPI technique (1.35 for GE and 1.33 for SE imaging). Performing quantitative VAI, we found that, among all VAI parametric maps, microvessel type indicator (MTI), distance map (I) and vascular-induced bolus peak-time shift (VIPS) were highly correlated. Likewise, VAI parametric maps of slope, slope length and short axis were highly correlated.ConclusionsMultiband accelerated SAGE successfully doubles the number of readout slices in the same measurement time when compared to conventional readout sequences. The corresponding VAI parametric maps provide insights into the complexity and heterogeneity of vascular changes in glioma.

PURPOSE:Functional MRI (fMRI) is a well-established method used to investigate localised brain activation by virtue of the blood oxygen level dependent (BOLD) effect. It often relies on visual presentations using beam projectors, liquid crystal display (LCD) screens, and goggle systems. In this study, we designed an MR compatible, low-cost display unit based on organic light-emitting diodes (OLED) and demonstrated its performance. METHODS:A 3.8" dual OLED module and an MIPI-to-HDMI converter board were used. The OLED module was enclosed using a shielded box to prevent noise emission from the display module and the potentially destructive absorption of high power RF from the MRI transmit pulses. The front of the OLED module was covered by a conductive, transparent mesh. Power was supplied from a non-magnetic battery. The shielding of the display was evaluated by directly measuring the electromagnetic emission with the aid of a pickup loop and a low noise amplifier, as well as by examining the signal-to-noise ratio (SNR) of phantom MRI data. The visual angle of the display was calculated and compared to standard solutions. As a proof of concept of the OLED display for fMRI, a healthy volunteer was presented with a visual block paradigm. RESULTS:The OLED unit was successfully installed inside a 3 T MRI scanner bore. Operation of the OLED unit did not degrade the SNR of the phantom images. The fMRI data suggest that visual stimulation can be effectively delivered to subjects with the proposed OLED unit without any significant interference between the MRI acquisitions and the display module itself. DISCUSSION:We have constructed and evaluated the MR compatible, dual OLED display for fMRI studies. The proposed OLED display provides the benefits of high resolution, wide visual angle, and high contrast video images during fMRI exams.

Quantitative imaging of the human brain is of great interest in clinical research as it enables the identification of a range of MR biomarkers useful in diagnosis, treatment and prognosis of a wide spectrum of diseases. Here, a 3D two-point method for water content and relaxation time mapping is presented and compared to established gold standard methods. The method determines free water content, H2O, and the longitudinal relaxation time, T1, quantitatively from a two-point fit to the signal equation including corrections of the transmit and receive fields. In addition, the effective transverse relaxation time, T2*, is obtained from an exponential fit to the multi-echo signal train and its influence on H2O values is corrected. The phantom results obtained with the proposed method show good agreement for H2O and T1 values with known and spectroscopically measured values, respectively. The method is compared in vivo to already established gold standard quantitative methods. For H2O and T2* mapping, the 3D two-point results were compared to a measurement conducted with a multiple-echo GRE with long TR and T1 is compared to results from a Look-Locker method, TAPIR. In vivo results show good overall agreement between the methods, but some systematic deviations are present. Besides an expected dependence of T2* on voxel size, T1 values are systematically larger in the 3D approach than those obtained with the gold standard method. This behaviour might be due to imperfect spoiling, influencing each method differently. Results for H2O differ due to differences in the saturation of cerebrospinal fluid and partial volume effects. In addition, ground truth values of in vivo studies are unknown, even when comparing to in vivo gold standard methods. A detailed region-of-interest analysis for H2O and T1 matches well published literature values.

Trimodal simultaneous acquisition of positron emission tomography (PET), magnetic resonance imaging (MRI), and electroencephalography (EEG) has become feasible due to the development of hybrid PET-MR scanners. To capture the temporal dynamics of neuronal activation on a millisecond-by-millisecond basis, an EEG system is appended to the quantitative high resolution PET-MR imaging modality already established in our institute. One of the major difficulties associated with the development of simultaneous trimodal acquisition is that the components traditionally used in each modality can cause interferences in its counterpart. The mutual interferences of MRI components and PET components on PET and MR images, and the influence of EEG electrodes on functional MRI images have been studied and reported on. Building on this, this study aims to investigate the influence of the EEG cap on the quality and quantification of PET images acquired during simultaneous PET-MR measurements. A preliminary transmission scan study on the ECAT HR+ scanner, using an Iida phantom, showed visible attenuation effect due to the EEG cap. The BrainPET-MR emission images of the Iida phantom with [18F]Fluordeoxyglucose, as well as of human subjects with the EEG cap, did not show significant effects of the EEG cap, even though the applied attenuation correction did not take into account the attenuation of the EEG cap itself.

The relatively high imaging speed of EPI has led to its widespread use in dynamic MRI studies such as functional MRI. An approach to improve the performance of EPI, EPI with Keyhole (EPIK), has been previously presented and its use in fMRI was verified at 1.5T as well as 3T. The method has been proven to achieve a higher temporal resolution and smaller image distortions when compared to single-shot EPI. Furthermore, the performance of EPIK in the detection of functional signals was shown to be comparable to that of EPI. For these reasons, we were motivated to employ EPIK here for high-resolution imaging. The method was optimised to offer the highest possible in-plane resolution and slice coverage under the given imaging constraints: fixed TR/TE, FOV and acceleration factors for parallel imaging and partial Fourier techniques. The performance of EPIK was evaluated in direct comparison to the optimised protocol obtained from EPI. The two imaging methods were applied to visual fMRI experiments involving sixteen subjects. The results showed that enhanced spatial resolution with a whole-brain coverage was achieved by EPIK (1.00 mm × 1.00 mm; 32 slices) when compared to EPI (1.25 mm × 1.25 mm; 28 slices). As a consequence, enhanced characterisation of functional areas has been demonstrated in EPIK particularly for relatively small brain regions such as the lateral geniculate nucleus (LGN) and superior colliculus (SC); overall, a significantly increased t-value and activation area were observed from EPIK data. Lastly, the use of EPIK for fMRI was validated with the simulation of different types of data reconstruction methods.

Artificial, anisotropic fibre phantoms are nowadays increasingly used in the field of diffusion-weighted MRI. Such phantoms represent useful tools for, among others, the calibration of pulse sequences and validation of diffusion models since they can mimic well-known structural features of brain tissue on the one hand, but exhibit a reduced complexity, on the other. Among all materials, polyethylene fibres have been widely used due to their excellent properties regarding the restriction of water diffusion and surface relaxation properties. Yet the magnetic susceptibility of polyethylene can be distinctly lower than that of distilled water. This difference produces strong microscopic, background field gradients in the vicinity of fibre bundles which are not parallel to the static magnetic field. This, in turn, modulates the MRI signal behaviour. In the present work we investigate an approach to reduce the susceptibility-induced background gradients via reducing the heterogeneity in the internal magnetic susceptibility. An aqueous solution of magnesium chloride hexahydrate (MgCl2·6H2O) is used for this purpose. Its performance is demonstrated in dedicated anisotropic fibre phantoms with different geometrical configurations.

Multi time-point pseudo-continuous arterial spin labelling (pCASL) with a Look-Locker EPI readout can sample the signal curve of blood kinetics at multiple time points after the labelling pulse. However, due to signal relaxation of labelled blood, the number of readout slices is limited. The aim of this study is to employ a multiband excitation technique to triple the number of readout slices in multi time-point pCASL. The multiband technique, along with 2-fold in-plane parallel imaging, was incorporated into the Look-Locker EPI for the multi time-point sampling of blood kinetic behaviour following the pCASL labelling scheme. The performance evaluation of the multiband and the single-band techniques were performed on four healthy subjects using a 32-channel head RF coil at 3T. Quantitative perfusion maps were analysed using a combination of labelling with and without flow suppression gradients. The perfusion maps provided by the multiband accelerated multi time-point pCASL were in good agreement with the conventional single-band technique. Multiband acceleration caused SNR loss but offered quantitative perfusion maps in 6.23 min with 18 slices compared with 6 slices within the same time period for the single-band method. As conclusion, the multiband technique can successfully triple the number of readout slices while achieving comparable perfusion data in the same measurement time as the conventional single-band readout.

Targeting toxic amyloid beta (Aβ) oligomers is currently a very attractive drug development strategy for treatment of Alzheimer´s disease. Using mirror-image phage display against Aβ1-42, we have previously identified the fully D-enantiomeric peptide D3, which is able to eliminate Aβ oligomers and has proven therapeutic potential in transgenic Alzheimer´s disease animal models. However, there is little information on the pharmacokinetic behaviour of D-enantiomeric peptides in general. Therefore, we conducted experiments with the tritium labelled D-peptide D3 (3H-D3) in mice with different administration routes to study its distribution in liver, kidney, brain, plasma and gastrointestinal tract, as well as its bioavailability by i.p. and p.o. administration. In addition, we investigated the metabolic stability in liver microsomes, mouse plasma, brain, liver and kidney homogenates, and estimated the plasma protein binding. Based on its high stability and long biological half-life, our pharmacokinetic results support the therapeutic potential of D-peptides in general, with D3 being a new promising drug candidate for Alzheimer´s disease treatment.

The investigation of tissue magnetic susceptibility and the resultant magnetic field offers a new avenue for quantitative tissue characterisation by MRI. One crucial step in mining the phase and field data for relevant tissue information is the correction of externally induced field shifts. This article outlines a multistep approach comprising several methodologies for background field removal. The virtues of B0 long-range variation detection and compensation of more localised external disturbances are unified in a sequential filter chain. The algorithm is tested by means of a numerical Monte Carlo simulation model and applied to in vivo measurements at 3T and 9.4T as well as to a fixed brain tissue measurement at 9.4T. Further, a comparison to conventional filter types has been undertaken.

Simultaneous, hybrid MR-PET is expected to improve PET image resolution in the plane perpendicular to the static magnetic field of the scanner. Previous papers have reported this either by simulation or experiment with simple sources and detector arrangements. Here, we extend those studies using a realistic brain phantom in a recently installed MR-PET system comprising a 9.4 T MRI-scanner and an APD-based BrainPET insert in the magnet bore. Point and line sources and a 3D brain phantom were filled with 18F (low-energy positron emitter), 68Ga (medium energy positron emitter) or 120I, a non-standard positron emitter (high positron energies of up to 4.6 MeV). Using the BrainPET insert, emission scans of the phantoms were recorded at different positions inside and outside the magnet bore such that the magnetic field was 0 T, 3 T, 7 T or 9.4 T. Brain phantom images, with the 'grey matter' compartment filled with 18F, showed no obvious resolution improvement with increasing field. This is confirmed by practically unchanged transaxial FWHM and 'grey/white matter' ratio values between at 0T and 9.4T. Field-dependent improvements in the resolution and contrast of transaxial PET images were clearly evident when the brain phantom was filled with 68Ga or 120I. The grey/white matter ratio increased by 7.3% and 16.3%, respectively. The greater reduction of the FWTM compared to FWHM in 68Ga or 120I line-spread images was in agreement with the improved contrast of 68Ga or 120I images. Notwithstanding elongations seen in the z-direction of 68Ga or 120I point source images acquired in foam, brain phantom images show no comparable extension. Our experimental study confirms that integrated MR-PET delivers improved PET image resolution and contrast for medium- and high-energy positron emitters even though the positron range is reduced only in directions perpendicular to the magnetic field.

The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS) being one of the key techniques. MRS permits the measurement of γ-aminobutyric acid (GABA) and glutamate levels, the central biochemical constituents of the excitation-inhibition balance in vivo. The inhibitory effects of GABA in the brain have been largely investigated in relation to the activity of resting state networks in functional magnetic resonance imaging (fMRI). In this study GABA concentration in the posterior cingulate cortex (PCC) was measured using single voxel spectra acquired with standard point resolved spectroscopy (PRESS) from 20 healthy male volunteers at 3 T. Resting state fMRI was consecutively measured and the values of GABA/Creatine+Phosphocreatine ratio (GABA ratio) were included in a general linear model matrix as a step of dual regression analysis in order to identify voxels whose neuroimaging metrics during rest were related to individual levels of the GABA ratio. Our data show that the connection strength of putamen to the default-mode network during resting state has a negative linear relationship with the GABA ratio measured in the PCC. These findings highlight the role of PCC and GABA in segregation of the motor input, which is an inherent condition that characterises resting state.

Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor imaging, giving new insights into the white matter microstructure and providing new biomarkers. Given the rapidly increasing number of studies, DKI has a potential to establish itself as a valuable tool in brain diagnostics. However, to become a routine procedure, DKI still needs to be improved in terms of robustness, reliability, and reproducibility. As it requires acquisitions at higher diffusion weightings, results are more affected by noise than in diffusion tensor imaging. The lack of standard procedures for post-processing, especially for noise correction, might become a significant obstacle for the use of DKI in clinical routine limiting its application. We considered two noise correction schemes accounting for the noise properties of multichannel phased-array coils, in order to improve the data quality at signal-to-noise ratio (SNR) typical for DKI. The SNR dependence of estimated DKI metrics such as mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) is investigated for these noise correction approaches in Monte Carlo simulations and in in vivo human studies. The intra-subject reproducibility is investigated in a single subject study by varying the SNR level and SNR spatial distribution. Then the impact of the noise correction on inter-subject variability is evaluated in a homogeneous sample of 25 healthy volunteers. Results show a strong impact of noise correction on the MK estimate, while the estimation of FA and MD was affected to a lesser extent. Both intra- and inter-subject SNR-related variability of the MK estimate is considerably reduced after correction for the noise bias, providing more accurate and reproducible measures. In this work, we have proposed a straightforward method that improves accuracy of DKI metrics. This should contribute to standardization of DKI applications in clinical studies making valuable inferences in group analysis and longitudinal studies.

Recent diffusion MRI studies of stroke in humans and animals have shown that the quantitative parameters characterising the degree of non-Gaussianity of the diffusion process are much more sensitive to ischemic changes than the apparent diffusion coefficient (ADC) considered so far as the "gold standard". The observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These studies were based on the novel non-Gaussian methods, such as diffusion kurtosis imaging (DKI) and log-normal distribution function imaging (LNDFI). As shown in our previous work investigating the animal stroke model, a combined analysis using two methods, DKI and LNDFI provides valuable complimentary information. In the present work, we report the application of three non-Gaussian diffusion models to quantify the deviations from the Gaussian behaviour in stroke induced by transient middle cerebral artery occlusion in rat brains: the gamma-distribution function (GDF), the stretched exponential model (SEM), and the biexponential model. The main goal was to compare the sensitivity of various non-Gaussian metrics to ischemic changes and to investigate if a combined application of several models will provide added value in the assessment of stroke. We have shown that two models, GDF and SEM, exhibit a better performance than the conventional method and allow for a significantly enhanced visualization of lesions. Furthermore, we showed that valuable information regarding spatial properties of stroke lesions can be obtained. In particular, we observed a stratified cortex structure in the lesions that were well visible in the maps of the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results provided evidence that cortical layers tend to be differently affected by ischemic processes.

Electroencephalography (EEG) frequencies have been linked to specific functions as an "electrophysiological signature" of a function. A combination of oscillatory rhythms has also been described for specific functions, with or without predominance of one specific frequency-band. In a simultaneous fMRI-EEG study at 3 T we studied the relationship between the default mode network (DMN) and the power of EEG frequency bands. As a methodological approach, we applied Multivariate Exploratory Linear Optimized Decomposition into Independent Components (MELODIC) and dual regression analysis for fMRI resting state data. EEG power for the alpha, beta, delta and theta-bands were extracted from the structures forming the DMN in a region-of-interest approach by applying Low Resolution Electromagnetic Tomography (LORETA). A strong link between the spontaneous BOLD response of the left parahippocampal gyrus and the delta-band extracted from the anterior cingulate cortex was found. A positive correlation between the beta-1 frequency power extracted from the posterior cingulate cortex (PCC) and the spontaneous BOLD response of the right supplementary motor cortex was also established. The beta-2 frequency power extracted from the PCC and the precuneus showed a positive correlation with the BOLD response of the right frontal cortex. Our results support the notion of beta-band activity governing the "status quo" in cognitive and motor setup. The highly significant correlation found between the delta power within the DMN and the parahippocampal gyrus is in line with the association of delta frequencies with memory processes. We assumed "ongoing activity" during "resting state" in bringing events from the past to the mind, in which the parahippocampal gyrus is a relevant structure. Our data demonstrate that spontaneous BOLD fluctuations within the DMN are associated with different EEG-bands and strengthen the conclusion that this network is characterized by a specific electrophysiological signature created by combination of different brain rhythms subserving different putative functions.

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs).EEG data were recorded simultaneously with fMRI from 16 healthy volunteers using MR compatible devices at 3 T. Tones with different SPLs were delivered to the volunteers and the N1/P2 amplitudes were included as covariates in the fMRI data analysis in order to compare the structures activated with high and low SPLs. Analysis of variance (ANOVA) and ROI analysis were also performed. Additionally, source localisation analysis was performed on the EEG data.The integration of averaged ERP parameters into the fMRI analysis showed an extended map of areas exhibiting covariation with the BOLD signal related to the auditory stimuli. The ANOVA and ROI analyses also revealed additional brain areas other than the primary auditory cortex (PAC) which were active with the auditory stimulation at different SPLs. The source localisation analyses showed additional sources apart from the PAC which were active with the high SPLs.The PAC and the insula play an important role in the processing of different SPLs. In the fMRI analysis, additional activation was found in the anterior cingulate cortex, opercular and orbito-frontal cortices with high SPLs. A strong response of the visual cortex was also found with the high SPLs, suggesting the presence of cross-modal effects.

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allow for a non-invasive investigation of cerebral functions with high temporal and spatial resolution. The main challenge of such integration is the removal of the pulse artefact (PA) that affects EEG signals recorded in the magnetic resonance (MR) scanner. Often applied techniques for this purpose are Optimal Basis Set (OBS) and Independent Component Analysis (ICA). The combination of OBS and ICA is increasingly used, since it can potentially improve the correction performed by each technique separately. The present study is focused on the OBS-ICA combination and is aimed at providing the optimal ICA parameters for PA correction in resting-state EEG data, where the information of interest is not specified in latency and amplitude as in, for example, evoked potential. A comparison between two intervals for ICA calculation and four methods for marking artefactual components was performed. The performance of the methods was discussed in terms of their capability to 1) remove the artefact and 2) preserve the information of interest. The analysis included 12 subjects and two resting-state datasets for each of them. The results showed that none of the signal lengths for the ICA calculation was highly preferable to the other. Among the methods for the identification of PA-related components, the one based on the wavelets transform of each component emerged as the best compromise between the effectiveness in removing PA and the conservation of the physiological neuronal content.

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has shown a number of advantages that make this multimodal technique superior to fMRI alone. The feasibility of recording EEG at ultra-high static magnetic field up to 9.4 T was recently demonstrated and promises to be implemented soon in fMRI studies at ultra high magnetic fields. Recording visual evoked potentials are expected to be amongst the most simple for simultaneous EEG/fMRI at ultra-high magnetic field due to the easy assessment of the visual cortex. Auditory evoked P300 measurements are of interest since it is believed that they represent the earliest stage of cognitive processing. In this study, we investigate the feasibility of recording visual evoked potentials and auditory evoked P300 in a 9.4 T static magnetic field. For this purpose, EEG data were recorded from 26 healthy volunteers inside a 9.4 T MR scanner using a 32-channel MR compatible EEG system. Visual stimulation and auditory oddball paradigm were presented in order to elicit evoked related potentials (ERP). Recordings made outside the scanner were performed using the same stimuli and EEG system for comparison purposes. We were able to retrieve visual P100 and auditory P300 evoked potentials at 9.4 T static magnetic field after correction of the ballistocardiogram artefact using independent component analysis. The latencies of the ERPs recorded at 9.4 T were not different from those recorded at 0 T. The amplitudes of ERPs were higher at 9.4 T when compared to recordings at 0 T. Nevertheless, it seems that the increased amplitudes of the ERPs are due to the effect of the ultra-high field on the EEG recording system rather than alteration in the intrinsic processes that generate the electrophysiological responses.

Parkinson's disease (PD) is characterized by typical extrapyramidal motor features and increasingly recognized non-motor symptoms such as working memory (WM) deficits. Using functional magnetic resonance imaging (fMRI), we investigated differences in neuronal activation during a motor WM task in 23 non-demented PD patients and 23 age- and gender-matched healthy controls. Participants had to memorize and retype variably long visuo-spatial stimulus sequences after short or long delays (immediate or delayed serial recall). PD patients showed deficient WM performance compared to controls, which was accompanied by reduced encoding-related activation in WM-related regions. Mirroring slower motor initiation and execution, reduced activation in motor structures such as the basal ganglia and superior parietal cortex was detected for both immediate and delayed recall. Increased activation in limbic, parietal and cerebellar regions was found during delayed recall only. Increased load-related activation for delayed recall was found in the posterior midline and the cerebellum. Overall, our results demonstrate that impairment of WM in PD is primarily associated with a widespread reduction of task-relevant activation, whereas additional parietal, limbic and cerebellar regions become more activated relative to matched controls. While the reduced WM-related activity mirrors the deficient WM performance, the additional recruitment may point to either dysfunctional compensatory strategies or detrimental crosstalk from "default-mode" regions, contributing to the observed impairment.