Publications

{Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here, we show such a spatially nonmonotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A nonmonotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes.}

{Using volumetric snapshot-GRE CEST MRI at 9.4T with high frequency sampling, we were able to separate novel CEST peaks at +2.7 ppm, +1.2 ppm and -1.7 ppm reliably in the CEST-spectrum and showed creation of maps of these CEST MRI contrasts in the healthy human brain to be feasible in vivo.}

{Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: \textquotedblleftfalse-positive\textquotedblright feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.}

{Timecourses that exhibit identical behaviour at distinct measurement occasions are reliable. Voodoo connectivity occurs when connectivity among brain regions exceeds within subject timecourse reliability. Thus, timecourse reliability limits the true detectable connectivity. We reproduced a working memory related connectome consisting of 561 paths obtained from 67 individuals. We tested \textgreater100000 fc-MRI pipelines and show that Savitzky Golay (SG) filters maximize true connectivity while conserving cognitively relevant changes of signals. This is noteworthy for approaches that focus on rapidly changing aspects of connectomes. Furthermore, SG filters detect zombie activity. These resting state oscillations are not under human control and contaminate working state signals. SPM filters exhibit more voodoo connectivity than SG filters. With the SPM filter based pipeline, we observed a connectivity of r\textequals0.44 and a poor true connectivity of r\textequals0.23, but with the SG pipeline we observed a connectivity of r\textequals0.59 and a fair true connectivity of r\textequals0.43. The number of paths detected with fair true connectivity (r \textgreater0.4) was 4 for the pipeline that was based on the SPM filter but 352 for the SG based pipeline. However, superior statistical properties of SG pipelines may not reflect neural reality. Hence, causal external validation of fc-MRI pipelines is crucial. Without such studies, different pipelines produce at best alternative maps.}

{Introduction: We require spatial problem solving skills regularly not only for common tasks, but also in dangerous circumstances such as emergency procedures, as the fire department encounters on a regular basis. Despite its importance, the topic has not been sufficiently investigated. Understanding the underlying cognitive processes that are involved in solving these problems will help provide supportive software and training methods to make collaborative spatial search more efficient and ideally less dangerous. Methods: The presented study aims to continue previous research conducted using two-dimensional means. We try to replicate previous findings in two experiments using an immersive virtual environment and investigate the extent of how a common reference frame can influence collaborative spatial search. Additionally, this study allows to examine how seeing your own orientation can influence spatial problem solving individually. Results: Results of two experiment suggest differences in performance between individual and collaborative search concerning complexity, showing a clear advantage of collaborative search when it comes to time, while the efficiency of each participant suffers greatly in these cases. A second experiment using common reference frames by introducing a compass-like arrow for collaborative search does not give a general advantage. The use of a compass may give a slight advantage for individuals in less complex environments. Discussion: It becomes clear that shared mental models do not automatically give an advantage in a realistic three-dimensional setting without training. Common reference frames should therefore not be generalized and need to be further investigated and differentiated to be integrated into supportive software or training methods.}

{A 3D snapshot CEST sequence is optimized for contrast originating from hydroxyl groups of glucose molecules. Multi-B1-multi-pH measurements allow fitting of exchange rates of four glucose hydroxyl groups, which are then used to optimize pre-saturation parameters in simulation. The optimal protocol gave highly reproducible signals in 6 healthy volunteers, and showed no contrast when tested in a brain tumor patient. This protocol provides a robust baseline for glucose injection studies.}

{Recently we demonstrated that a selective detection of endogenous bulk mobile proteins in living tissue can be realized by the novel approach of dual-frequency irradiation CEST (dualCEST)-MRI1 without contamination of saturation transfer effects of metabolites, lipids and semi-solids. For this approach, specificity is achieved by measuring the intramolecular magnetization transfer (i.e. saturation crosstalk T) between CEST signals resonating at two different frequency offsets $\Delta$$\omega$ and $\Delta$$\omega$c (Fig. 1a). Such a non-invasive imaging technique may be of particular interest for the detection of pathological alterations of protein expression, such as in neurodegenerative diseases or cancer. Until now, application in clinical trials was prevented by the inherently small signal-to-noise ratio (SNR) in comparison to conventional CEST approaches. Here, we present further developments in signal preparation, image acquisition and post-processing techniques enabling dualCEST examinations in a reasonable and clinicallyrelevant time frame.}

{In this study the acquisition of high resolution (64x64) metabolite maps at 9.4T using a non-lipid suppressed ultra-short TR and TE 1H FID MRSI sequence is accelerated using an improved over-discretized SENSE reconstruction and B0 correction method. The improved reconstruction is compared to conventional SENSE and GRAPPA reconstruction, and reproducible metabolite maps are acquired using this technique.}

{The aim of this work was to use post-processing methods to improve the data quality of metabolite maps acquired on the human brain at 9.4 T with accelerated acquisition schemes. This was accomplished by combining an improved sensitivity encoding (SENSE) reconstruction with a B0 correction of spatially over-discretized magnetic resonance spectroscopic imaging (MRSI) data. Since MRSI scans suffer from long scan duration, investigating different acceleration techniques has recently been the focus of several studies. Due to strong B0 inhomogeneity and strict specific absorption rate (SAR) limitations at ultra-high fields, the use of a low-SAR sequence combined with an acceleration technique that is compatible with dynamic B0 shim updating is preferable. Hence, in this study, a non-lipid-suppressed ultra-short TE and TR 1H free induction decay MRSI sequence is combined with an in-plane SENSE acceleration technique to obtain high-resolution metabolite maps in a clinically feasible scan time. One of the major issues in applying parallel imaging techniques to non-lipid-suppressed MRSI is the presence of strong lipid aliasing artifacts, which if not thoroughly resolved will hinder the accurate quantification of the metabolites of interest. To achieve a more robust reconstruction, an over-discretized SENSE reconstruction (with direct control over the shape of the spatial response function) was combined with an over-discretized B0 correction. This method is compared with conventional SENSE reconstruction for seven acceleration schemes on four healthy volunteers. The over-discretized method consistently outperformed conventional SENSE, resulting in an average of 23 $\pm$ 1.2\textpercent higher signal-to-noise ratio and 8 $\pm$ 2.9\textpercent less error in the fitting of the N-acetylaspartate signal over a whole brain slice. The highest achievable acceleration factor with the proposed technique was determined to be 4. Finally, using the over-discretized method, high-resolution (97 $\mu$L nominal voxel size) metabolite maps can be acquired in 3.75 min at 9.4 T. This enables the acquisition of high-resolution metabolite maps with more spatial coverage at ultra-high fields.}

{Purpose To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. Methods A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. Results A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T1 of water and B1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer\textendashweighted imaging. Conclusion Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo.}

{NMR is one of the most versatile and useful physical effects used for human imaging, chemical analysis and the elucidation of molecular structures. Yet, the full potential of NMR is hardly ever used, because only a small fraction of the nuclear spin ensemble is polarized - i.e. aligned with the applied static magnetic field. This fraction is termed nuclear spin polarization P. As a result, no more than a few parts per million of all nuclear spins effectively contribute to the signal in all magnetic fields (B0) available for NMR or MRI today. Because P is approximately linear with B0, a stronger field offers some but limited improvements. Hyperpolarization methods seek other means to increase P and thus the MR signal. A unique source of pure spin order is the spin singlet state of dihydrogen, parahydrogen (pH2), which is inherently stable and long-lived. When brought into contact with another molecule, this "spin order on demand" allows enhancing the NMR signal by several orders of magnitude. In contrast to other methods, this process is very fast (seconds) and can take place in the liquid state. Nuclear spin polarization of the order of unity was demonstrated, manifesting as significant NMR and MRI signal enhancement by several orders of magnitude. Considerable progress was made in the past decade in the area of pH2-based hyperpolarization techniques for biomedical applications. It is the goal of this minireview to provide a comprehensive, selective overview of these developments, covering the areas of spin physics, catalysis, instrumentation, contrast agents\textquotesingle preparation and application.}

{The role of lateral prefrontal cortex (LPFC) in mediating conscious perception has been recently questioned due to potential confounds resulting from the parallel operation of task related processes. We have previously demonstrated encoding of contents of visual consciousness in LPFC neurons during a no-report task involving perceptual suppression. Here, we report a separate LPFC population that exhibits task-phase related activity during the same task. The activity profile of these neurons could be captured as canonical response patterns (CRPs), with their peak amplitudes sequentially distributed across different task phases. Perceptually suppressed visual input had a negligible impact on sequential firing and functional connectivity structure. Importantly, task-phase related neurons were functionally segregated from the neuronal population, which encoded conscious perception. These results suggest that neurons exhibiting task-phase related activity operate in the LPFC concurrently with, but segregated from neurons representing conscious content during a no-report task involving perceptual suppression.}

{When a stimulus has two competing interpretations, perception tends to alternate over time: bistable perception. A special case hereof occurs when the two eyes receive differing information in the same retinal space, perception also alternates: binocular rivalry (BR). Functional magnetic resonance imaging (fMRI) studies have shown the right anterior intraparietal sulcus (IPS) as well as posterior superior parietal lobule (SPL) activated during perceptual transitions. However, the causal role of these regions remains unclear, as distinct transcranial magnetic stimulation (TMS) studies have reported either shortening or lengthening TMS effects on perceptual dominance durations. Reasons for these divergent results may lie in the use of different stimuli or of distinct TMS protocols. Here we tested effects of a single, inhibitory TMS protocol, continuous theta burst stimulation (cTBS), applied to the IPS, SPL, and vertex control on distinct classes of bistable perception in three separate samples of participants (total N \textequals 52). In sample one we used structure from motion (SFM) bistable perception, in sample two BR between random dots that was either reported, unreported or unreportable, and in sample three both of the above stimuli as well as BR between flickering checkerboards. Contrary to our expectation, cTBS neither consistently affected dominance durations across the stimuli, test sites, nor samples. This null effect was supported by Bayes factors. In a last experiment we correlated participants\textquoteright cTBS induced change in BR dominance with the change in motor-evoked potentials (MEP) following cTBS to primary motor cortex. While MEP amplitude was reduced, corroborating the inhibitory effect of cTBS, we observed no correlation with the cTBS effect on BR. Given the comparably large N used in the present study, the replication of our null-finding across several classes of bi-stable stimuli, and the lack of correlation of cTBS effects between motor and parietal cortex, the present findings cast doubt on the efficacy of the cTBS protocol over parietal cortex and the generalisation of cTBS effects from motor to parietal cortex.}

{Introduction: Magnetic resonance spectroscopy (MRS) measurements of excitatory and inhibitory neurotransmission may provide valuable insights into the underlying neurobiology of altered functional connectivity in psychiatric disorders. Consequently, local measures of glutamate (Glu) and GABA are often reported to moderate resting-state functional connectivity measures (Duncan et al., 2013; Horn et al., 2010; Kapogiannis et al., 2013). However, the inherently low signal-to-noise ratio of conventional MRS measurements necessitates voxel sizes far exceeding those of fMRI measurements, leading to crude measures of local neurometabolism. Here, we tested the hypothesis that decomposing the pregenual anterior cingulate\textquotesingles (pgACC) functional connectome into a more fine-grained fMRI-based resolution provides incremental information on the neurotransmitters governing its function. To this end, we employed a novel, data-driven approach that aims to predict (pgACC) glutamatergic and GABAergic signatures by assigning weights to seed-voxel connections according to their predictive power. Methods: 77 healthy participants underwent an MRI protocol consisting of structural, functional, and MRS measurements at 7 Tesla. The MRS voxel (20 x 15 x 10 mm3) was placed in the pgACC according to a previously established protocol (Dou et al., 2013). GABA and Glu levels were fitted using the LCModel software (Provencher, 2001) and expressed relative to total creatine. GABA measures were log transformed. We used the default CONN pipeline (Whitfield-Gabrieli et al., 2012) for fMRI preprocessing without smoothing. Data were then z-scored, despiked, and detrended, after which six motion parameters were regressed out. We created a composite mask of each subject\textquotesingles MRS mask for subsequent analyses. As seed voxels, we selected only those fMRI voxels in the composite MRS mask. The time series of the seed voxels were correlated with mean time series of the 132 CONN atlas nodes. To account for the statistical redundancy of the voxel-based predictor matrix, we employed PLS regression, which projects the predictor variables into a latent space (similar to principal component analysis) while optimizing the prediction of the outcome. We entered the resulting connectivity matrices into two PLS regression models (McIntosh et al., 2004) using 1 component to predict pgACC Glu or GABA. To statistically assess the obtained model fit (residual sum of squares), we performed a permutation test with 1000 permutations of the outcome measure. Conclusions: A novel, data-driven approach employing PLS regression allowed us to predict Glu, but not GABA from the functional connectivity profiles of pgACC seed voxels. For Glu, the resulting weight matrix showed that a widespread pattern of functional connectivity contributes to the successful prediction of local glutamate suggesting that glutamate levels might have a diffuse global effect on functional connectivity. Further analyses will be performed to cross-validate the prediction models and explore whether specific seed voxels in the pgACC have higher predictive power than others.}

{A pedophilic disorder is characterised by abnormal sexual urges towards prepubescent children. Child abusive behavior is frequently a result of lack of behavioral inhibition and current treatment options entail, next to suppressing unchangeable sexual orientation, measures to increase cognitive and attentional control. We tested, if in brain regions subserving attentional control of behavior and perception of salient stimuli, such inhibition deficit can be observed also on the level of inhibitory neurotransmitters. We measured GABA concentration in the dorsal anterior cingulate cortex (dACC) and in a control region, the pregenual anterior cingulate cortex (pgACC) in pedophilic sex offenders (N \textequals 13) and matched controls (N \textequals 13) using a 7 Tesla STEAM magnetic resonance spectroscopy (MRS). In dACC but not in the control region pedophilic sex offenders showed reduced GABA/Cr concentrations compared to healthy controls. The reduction was robust after controlling for potential influence of age and gray matter proportion within the MRS voxel (p \textless 0.04). Importantly, reduced GABA/Cr in patients was correlated with lower self-control measured with the Barratt Impulsiveness Scale (p \textequals 0.028, r \textequals \textminus0.689). In a region related to cognitive control and salience mapping, pedophilic sex offenders showed reduction of the inhibitory neurotransmitter GABA which may be seen as a neuronal correlate of inhibition and behavioral control.}

{According to a long-standing hypothesis in motor control, complex body motion is organized in terms of movement primitives, reducing massively the dimensionality of the underlying control problems. For body movements, this low-dimensional organization has been convincingly demonstrated by the learning of low-dimensional representations from kinematic and EMG data. In contrast, the effective dimensionality of dynamic facial expressions is unknown, and dominant analysis approaches have been based on heuristically defined facial \textquotedblleftaction units,\textquotedblright which reflect contributions of individual face muscles. We determined the effective dimensionality of dynamic facial expressions by learning of a low-dimensional model from 11 facial expressions. We found an amazingly low dimensionality with only two movement primitives being sufficient to simulate these dynamic expressions with high accuracy. This low dimensionality is confirmed statistically, by Bayesian model comparison of models with different numbers of primitives, and by a psychophysical experiment that demonstrates that expressions, simulated with only two primitives, are indistinguishable from natural ones. In addition, we find statistically optimal integration of the emotion information specified by these primitives in visual perception. Taken together, our results indicate that facial expressions might be controlled by a very small number of independent control units, permitting very low-dimensional parametrization of the associated facial expression.}

{In binocular rivalry, our perception alternates spontaneously between mutually exclusive or mixed interpretations, although the physical stimulus remains constant. This enables us to study visual consciousness, as it allows for a dissociation between sensory processing and conscious perception [1]. Previous imaging studies in humans have implicated the role of the fronto-parietal network in mediating perceptual alternations [2]. However, whether this frontal activation is indeed related to the percept, or, rather is confounded by, or reflects the consequences of perception viz. decision-making, introspection or motor-output, is still a matter of debate [3, 4]. Moreover, the degree of modulation in the frontal regions at the spiking and perisynaptic activity timescales is yet unclear. Because of the above-mentioned considerations, two male macaques were trained to maintain fixation within a window and follow the motion of the stimulus for up to 12 seconds in a specifically designed no-report paradigm. They were implanted with Utah Arrays (10 $\times$ 10) in the ventro-lateral prefrontal cortex. Spontaneous switches in the percept were identified from the Optokinetic Nystagmus traces. Trials where the stimulus was experimentally switched acted as a control. Sites on the array were sorted according to their preference for either an upwardmoving or a downward-moving stimulus based on the spiking activity. In the high-frequency regime, i.e. the Gamma band (80\textendash150 Hz), the power followed the pattern of selectivity displayed by the neural discharges including adaptation as reported previously [4]. Activity preceding a spontaneous switch revealed epochs of power modulations in the low-frequencies, i.e. the Delta Band (1\textendash4 Hz) and the Theta Band (4\textendash8 Hz), whereas this activity manifested itself strongly post-switch during physical alternation, pointing towards a role of slow cortical states in refreshing the content of conscious visual perception. Moreover, this burst-like activity was stronger when a preferred stimulus switched to a non-preferred stimulus implicating these slow cortical states in specifically overcoming an energy barrier required to transition from a preferred to a non-preferred stimulus. Taken together, these results strongly suggest that oscillatory activity in the prefrontal cortex plays a central role in the spontaneous transitions in conscious visual perception.}

{BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined. METHODS: In an observational case-control study, we recruited 37 patients with prior (\textgreater12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac 31P-spectroscopy. RESULTS: Participants were predominantly middle-age (64$\pm$11 years) women (97). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the study, the majority (88) of patients had persisting symptoms compatible with heart failure (median of 13 [range 0-76] in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24$\pm$1.3 versus 31$\pm$1.3 mL/kg/min, P\textless0.001; increased VE/VCO2 slope, 31$\pm$1 versus 26$\pm$1, P\textequals0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, \textendash16$\pm$1.0 versus \textendash23$\pm$1.5, P\textless0.001; global longitudinal strain, \textendash17$\pm$1 versus \textendash20$\pm$1, P\textequals0.006), increased native T1 mapping values (1264$\pm$10 versus 1184$\pm$10 ms, P\textless0.001), and impaired cardiac energetic status (phosphocreatine/$\gamma$-adenosine triphosphate ratio, 1.3$\pm$0.1 versus 1.9$\pm$0.1, P\textless0.001). CONCLUSIONS: In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype.}

{Mental Rotation (i.e. the ability to mentally rotate representations of 2D and 3D objects) and egocentric Perspective Taking (i.e. the ability to adopt an imagined spatial perspective) represent the two most well-known and used types of spatial transformation. Yet, these two spatial transformations are conceptually, visually, and mathematically equivalent. Thus, an active debate in the field is whether these two types of spatial transformations are cognitively and neurally distinct or whether they represent different manifestation of the same underlying core mental process. In this study, we utilize a machine learning approach to extract neural activity from electroencephalography (EEG) measures and identify neural differences between mental rotation and perspective taking tasks. Our results provide novel empirical evidence in support of the view that these two types of spatial transformation correspond to district cognitive processes at the neural level. Importantly, the proposed framework provides a novel approach that can facilitate the study of the neural correlates of spatial cognition.}

{Even a small frequency drift of less than 1Hz/min of the MRI scanner can have a strong impact on gagCEST measurements. We propose a dynamic B0-correction that tracks the frequency shift using the phase images provided by the GRE readout. We show that this correction eliminates the influence of the frequency drift on gagCEST without the need of additional measurement time allowing higher accuracy, reproducibility, and comparability of gagCEST studies.}

{In this paper we present a generic Port-Hamiltonian (PH) model that includes cable dynamics (in particular elasticity and couplings with the platform and all cables among each other) of a cable-driven parallel robot (CDPR), which is used as a motion simulator. Moreover we consider changes in the cable parameters, i.e. it\textquoterights elasticity, mass and length when the cables are wound/unwound from the winches. To the best of our knowledge nobody considered such a detailed and generic model of a CDPR in PH structure before. Since motion simulators are built to mimic systems with different physical properties, PH modeling can pave the way for physics-shaping controllers.}

{Functional localizers are particularly prevalent in functional magnetic resonance imaging (fMRI) studies concerning face processing. In this study, we extend the knowledge on face localizers regarding four important aspects: First, activation differences in occipital and fusiform face areas (OFA/FFA) and amygdala are characterized by increased activation while precuneus and medial prefrontal cortex show decreased deactivation to faces versus control stimuli. The face-selective posterior superior temporal sulcus is a hybrid area exhibiting increased activation within its inferior and decreased deactivation within its superior part. Second, the employed control stimuli can impact on whether a region is classified as face-selective or not. We specifically investigated this for recently described subregions of the FFA (FFA-1/FFA-2). While FFA-2 responded stronger to faces than to objects, houses, or landscapes, FFA-1 was only detected with landscapes as control condition. Third, reproducibility of individual peak activations is excellent for right FFA and quite good for right OFA, whereas within all other areas it was too low to provide valid information on time-invariant individual peaks. Finally, the fine-grained spatial activation patterns in right OFA and FFA are both time-invariant within each individual and sufficiently different between individuals to enable identification of individual participants with near-perfect precision (fMRI fingerprinting).}

{Magnetic resonance imaging and spectroscopic techniques are widely used in humans both for clinical diagnostic applications and in basic research areas such as cognitive neuroimaging. In recent years, new human MR systems have become available operating at static magnetic fields of 7 T or higher ($\geq$300 MHz proton frequency). Imaging human-sized objects at such high frequencies presents several challenges including non-uniform radiofrequency fields, enhanced susceptibility artifacts, and higher radiofrequency energy deposition in the tissue. On the other side of the scale are gains in signal-to-noise or contrast-to-noise ratio that allow finer structures to be visualized and smaller physiological effects to be detected. This review presents an overview of some of the latest methodological developments in human ultra-high field MRI/MRS as well as associated clinical and scientific applications. Emphasis is given to techniques that particularly benefit from the changing physical characteristics at high magnetic fields, including susceptibility-weighted imaging and phase-contrast techniques, imaging with X-nuclei, MR spectroscopy, CEST imaging, as well as functional MRI. In addition, more general methodological developments such as parallel transmission and motion correction will be discussed that are required to leverage the full potential of higher magnetic fields, and an overview of relevant physiological considerations of human high magnetic field exposure is provided.}

{Magnetic Resonance Spectroscopy (MRS) allows for a non-invasive and non-ionizing determination of in vivo tissue concentrations and metabolic turn-over rates of more than 20 metabolites and compounds in the central nervous system of humans. The aim of this review is to give a comprehensive overview about the advantages, challenges and advances of ultra-high field MRS with regard to methodological development, discoveries and applications from its beginnings around 15 years ago up to the current state. The review is limited to human brain and spinal cord application at field strength of 7T and 9.4T and includes all relevant nuclei (1H, 31P, 13C).}

{Automated systems are often designed to reduce "cognitive workload" in their users. What does this mean? In my talk, I present research that demonstrates how theory and psychophysiological methods (i.e., eye tracking, heart rate, and EEG/ERP) can lend better definition to the cognitive mechanisms that human-machine interfaces support. Three examples will be provided from the task domains of: (1) instrumented cockpit display, auditory cues for task-management, and manual assembly instructions. The first study shows that overt attention planning across single-sensor-single-instrument is compromised by high anxiety and working memory load, suggesting a need for glass cockpit systems that adapt to user states [1]. The second study uses ERP methods to re-investigate whether auditory notifications that were originally designed for supporting and cueing task management ought to necessarily favor verbal commands instead of iconic sounds [2]. Contrary to the designers\textquotesingle original findings, we found that verbal commands were more likely to capture early attention while auditory icons resulted in stronger working memory updating. The third study demonstrates how we used EEG methods to understand the cognitive benefits of using an in situ display system for manual assembly, which provides assembly instructions in real-time [3]. Specifically, we showed that it reduces working memory load in its users. Altogether, these examples represent the diversity of "cognitive workload", across different scenarios. While "cognitive workload" is an intuitive concept, I will argue that it is not a useful concept in designing automated systems, especially as we strive towards automating cognitive processes that are intended to replace or augment ours.}

{Purpose Chemical exchange saturation transfer (CEST) NMR or MRI experiments allow detection of low concentrated molecules with enhanced sensitivity via their proton exchange with the abundant water pool. Be it endogenous metabolites or exogenous contrast agents, an exact quantification of the actual exchange rate is required to design optimal pulse sequences and/or specific sensitive agents. Methods Refined analytical expressions allow deeper insight and improvement of accuracy for common quantification techniques. The accuracy of standard quantification methodologies, such as quantification of exchange rate using varying saturation power or varying saturation time, is improved especially for the case of nonequilibrium initial conditions and weak labeling conditions, meaning the saturation amplitude is smaller than the exchange rate ($\gamma$B1 \textless k). Results The improved analytical \textquoteleftquantification of exchange rate using varying saturation power/time\textquoteright (QUESP/QUEST) equations allow for more accurate exchange rate determination, and provide clear insights on the general principles to execute the experiments and to perform numerical evaluation. The proposed methodology was evaluated on the large-shift regime of paramagnetic chemical-exchange-saturation-transfer agents using simulated data and data of the paramagnetic Eu(III) complex of DOTA-tetraglycineamide. Conclusions The refined formulas yield improved exchange rate estimation. General convergence intervals of the methods that would apply for smaller shift agents are also discussed.}

{Introduction: Subcortical brain regions are absolutely essential for normal human cognitive function. Blood oxygen level dependent (BOLD) functional MRI (fMRI) can be a useful tool to understand subcortical neurovascular response. The hemodynamic response function (HRF) is crucial for the interpretation of fMRI results. The HRF is the vascular response evoked by brief (few sec) neural activation and is formed by changes in oxygen uptake and blood flow. The HRF should be a good indicator of brain health, because neurovascular coupling is critical for brain function (Carusone, Srinivasan et al. 2002, Roc, Wang et al. 2006, Bonakdarpour, Parrish et al. 2007). A substantial delayed HRF with lower hyperoxic peak was shown in stroke, mild cognitive impairment, and Alzheimer\textquotesingles disease patients. However, the relationship between the HRF and vascular pathology has not yet been quantitatively characterized. It is clear that we need a better understanding of the underlying physiological processes that gives rise to the HRF in human subcortical regions. Methods: Imaging was performed on a 3T (Baylor College of Medicine) and 9.4T (Max Planck Institute). For 3T, functional images were obtained using a 2-shot spiral acquisition (34-ms acquisition time for each shot) for 1.5 mm3 spatial resolution (TE 35 ms, TR 750 ms, volume acquisition every 1.5 s). Functional images were also obtained at 9.4T using point spread function (PSF)-corrected EPI with 1 mm3 spatial resolution (TE 21 ms, TR 1250 ms). Both of them cover subcortical regions including superior colliculus (SC), inferior colliculus (IC) and lateral geniculate nucleus (LGN). To generate brief periods of neural activity, subjects perform a multi-sensory integration task every 30 s. During a 2-s duration stimulation period, three circular regions (5\textordmasculine radius) filled with flickering colored dots are presented in random order at different screen locations with corresponding band pass-filtered white-noise audio pulses. Subjects performed saccades to fixate on each flickering circle (without moving their heads) and pushed a response button corresponding to the color of the flickering circle. Thus, the task requires subject to integrate auditory and visual inputs to perform visual and somatosensory tasks. This 30-s duration trial was repeated 18 times in each run; 5 runs will be collected. HRFs obtained in the target regions were temporally averaged over the whole of the scanning session. The peak amplitude and time parameters (e.g. time-to-peak, full width at half-maximum) of HRFs were obtained. Results: We were able to measure subcortical HRFs at both 3T and 9T scanners; the signal-to-noise ratios are \textasciitilde3 at 3T and \textasciitilde8 at 9.4T. At 3T, peak amplitude and time-to-peak of HRFs are relatively stable and similar throughout SC, and LGN, but IC shows less reliable and spatially discontinuous peak amplitude and relatively slow time-to-peak, Fig. 1. We also compared HRFs in SC with HRFs in early visual areas for both 3T and 9.4T. Faster hyperoxic peaks and narrower full-width-half-max (FWHM) and weak undershoot (Fig 2, blue and red lines) are shown comparing with those in early visual areas (purple and cyan lines). Note that peak amplitude of the HRF in SC at 9.4T is \textasciitilde20 stronger than that at 3T. Conclusions: We demonstrate reliable HRFs in subcortical regions at both 3T and 9.4T scanners. The HRFs in subcortical regions show significant different from those in early visual cortex, which indicates that dynamics of neurovascular coupling in subcortical regions can be different from early visual areas. This suggests a separate characterization for subcortical HRFs required. Here, our metrics successfully characterize subcortical HRFs, which can be a useful tool for assessment of subcortical vascular health.}

{Quantification of magnetic resonance spectroscopy signals using the phantom replacement method requires an adequate correction of differences between the acquisition of the reference signal in the phantom and the measurement in vivo. Applying the principle of reciprocity, sensitivity differences can be corrected at low field strength by measuring the RF transmitter gain needed to obtain a certain flip angle in the measured volume. However, at higher field strength the transmit sensitivity may vary from the reception sensitivity, which leads to wrongly estimated concentrations. To address this issue, a quantification approach based on the principle of reciprocity for use at 3T is proposed and validated thoroughly. In this approach, the RF transmitter gain is determined automatically using a volume-selective power optimization and complemented with information from relative reception sensitivity maps derived from contrast-minimized images to correct differences in transmission and reception sensitivity. In this way, a reliable measure of the local sensitivity was obtained. The proposed method is used to derive in vivo concentrations of brain metabolites and tissue water in two studies with different coil sets in a total of 40 healthy volunteers. Resulting molar concentrations are compared with results using internal water referencing (IWR) and Electric REference To access In vivo Concentrations (ERETIC). With the proposed method, changes in coil loading and regional sensitivity due to B1 inhomogeneities are successfully corrected, as demonstrated in phantom and in vivo measurements. For the tissue water content, coefficients of variation between 2 and 3.5 were obtained (0.6\textendash1.4 in a single subject). The coefficients of variation of the three major metabolites ranged from 3.4\textendash14.5. In general, the derived concentrations agree well with values estimated with IWR. Hence, the presented method is a valuable alternative for IWR, without the need for additional hardware such as ERETIC and with potential advantages in diseased tissue.}

{In this paper we present the implementation of a model predictive controller (MPC) for real-time control of a motion simulator based on a serial robot with 8 degrees of freedom. The goal of the controller is to accurately reproduce six reference signals simultaneously (the accelerations and angular velocities in the body frame of reference) taken from a simulated or real vehicle, by moving the human participant sitting inside the cabin located at the end effector. The controller computes the optimal combined motion of all axes while keeping the axis positions, velocities and accelerations within their limits. The motion of the axes is computed every 12ms based on a prediction horizon consisting of 60 steps, spaced 48ms apart, thus looking ahead 2.88s. To evaluate tracking performance, we measured the acceleration and angular velocity in the cabin using an Inertial Measurement Unit (IMU) for synthetic (doublets and triangle-doublets) and realistic (recorded car and helicopter maneuvers) reference signals. We found that fast-changing acceleration inputs excite the natural frequencies of the system, leading to severe mechanical oscillations. These oscillations can be modelled by a second-order LTI system and mitigated by including this model in the controller. The use of proper algorithms and software allows the computations to be done in real-time.}

Magnetic resonance imaging (MRI) is moving towards higher and higher eld strengths. After 1.5T MRI scanners b ecame commonplace, 3T scanners were intro duced and once 3T scanners b ecame commonplace, ultra high eld (UHF) scanners were intro duced. UHF scanners typically refer to scanners with a eld strength of 7T or higher. The numb er of sites that utilise UHF scanners is slowly growing and the rst 7T MRI scanners were recently CE certied for clinical use. Although UHF scanners have the b enet of higher signal-to-noise ratio (SNR), they come with their own challenges. One of the many challenges is the prob- lem of inhomogeneity of the main static magnetic eld (B0 eld). This thesis addresses multiple asp ects asso ciated with the problem of B0 inhomogeneity. The pro cess of homogenising the eld is called shimming. The fo cus of this thesis is on active shimming where extra shim coils drive DC currents to gen- erate extra magnetic elds sup erimp osed on the main magnetic eld to correct for inhomogeneities. In particular, we lo oked at the following issues: algorithms for calculating optimal shim currents; global static shimming using very high order/degree spherical harmonic-based (VHOS) coils; dynamic slice-wise shim- ming using VHOS coils compared to a lo calised multi-coil array shim system; B0 eld monitoring using an NMR eld camera; characterisation of the shim system using a eld camera; and designing a controller based on the shim system mo del for real-time feedback. We hop e that, after reading this thesis, the reader will b ecome well-informed in the practical implementation and limitations of B0 shimming at 9.4T in the human brain.

{As patients with WHO IV\mbox{$^\circ$} gliomas are still having a dismal prognosis, further tumor characterization is needed. With prognosis and histopathological parameters being dependent on tumor localization, and Chemical-Exchange-Saturation-Transfer(CEST) MRI at 7T being one of the latest advances in tumor imaging, we have prospectively evaluated CEST signals in 21 patients. Amide CEST and ADC parameters are significantly different with regard to brain hemispheres and correlating. CEST NOE(Nuclear Overhauser-Effect) is not different with regard to brain hemispheres, but in case of contact to the subventricular zone, which is accompanied by worse prognosis. NOE is possibly showing complementary information to Amide CEST.}

{Purpose: To investigate the localization dependence of relaxationcompensated multi-pool Chemical-Exchange-Saturation-Transfer (CEST) MRI at 7T and histopathological parameters in newly diagnosed untreated WHO IV\mbox{$^\circ$} glioma patients. Methods and Materials: Twenty patients with newly diagnosed WHO IV\mbox{$^\circ$} gliomas were prospectively included in this study and investigated at a 7T whole-body scanner (Siemens Healthcare, Erlangen, Germany). Mean CEST signal intensities (Nuclear-Overhauser-Effect(NOE), Amide-Proton- Transfer(APT), Downfield\textunderscoreNOE-suppressed APT(DNS\textunderscoreAPT)), ADC parameters and histopathological parameters of the tumor volumes were evaluated with regard to extension, localization (brain hemisphere and lobe) and contact to the subventricular zone using non-parametric Mann-Whitney tests, ANOVA on ranks test and Spearman correlation. Results: Mean CEST APT\&DNS\textunderscoreAPT signal intensities (0,156$\pm$0,118 \& 0,137$\pm$0,116) were significantly increased in right vs. left hemisphere glioblastomas (0,072$\pm$0,014 \& 0,048$\pm$0,014), (p\textequals0,044 and 0,010). Mean ADC parameter were significantly decreased in right vs. left hemisphere glioblastomas (1,04\textasteriskcentered10\textasciicircum7$\pm$0,08\textasteriskcentered10\textasciicircum7 vs. 1,18\textasteriskcentered10\textasciicircum7$\pm$0,12\textasteriskcentered10\textasciicircum7) (p\textequals0,046). Mean CEST NOE signal intensity didn\textquoterightt differ significantly between both hemispheres, but was significantly increased in case of subventricular zone contact (0,101$\pm$0,015 vs. 0,118$\pm$0,015) (p\textequals0,037). The lobe localization and extension of the tumor had no significant effect on CEST and ADC signals. CEST APT\&DNS\textunderscoreAPT and ADC signal intensities did significantly correlate (- 0,67 and -0,56) (p\textless0,01), but not CEST NOE and ADC parameters. Histopathological parameters were not significantly different with regard to different localizations. Conclusion: Relaxation-compensated multi-pool CEST MRI signal depends on the anatomic localization. Amide CEST and ADC are positively correlating - NOE parameters are solemly different with regard to subventricular zone contact, possibly showing complementary information to Amide CEST and ADC.}

{Behaviorally, it is well established that human observers integrate signals near-optimally weighted in proportion to their reliabilities as predicted by maximum likelihood estimation. Yet, despite abundant behavioral evidence, it is unclear how the human brain accomplishes this feat. In a spatial ventriloquist paradigm, participants were presented with auditory, visual, and audiovisual signals and reported the location of the auditory or the visual signal. Combining psychophysics, multivariate functional MRI (fMRI) decoding, and models of maximum likelihood estimation (MLE), we characterized the computational operations underlying audiovisual integration at distinct cortical levels. We estimated observers\textquotesingle behavioral weights by fitting psychometric functions to participants\textquotesingle localization responses. Likewise, we estimated the neural weights by fitting neurometric functions to spatial locations decoded from regional fMRI activation patterns. Our results demonstrate that low-level auditory and visual areas encode predominantly the spatial location of the signal component of a region\textquotesingles preferred auditory (or visual) modality. By contrast, intraparietal sulcus forms spatial representations by integrating auditory and visual signals weighted by their reliabilities. Critically, the neural and behavioral weights and the variance of the spatial representations depended not only on the sensory reliabilities as predicted by the MLE model but also on participants\textquotesingle modality-specific attention and report (i.e., visual vs. auditory). These results suggest that audiovisual integration is not exclusively determined by bottom-up sensory reliabilities. Instead, modality-specific attention and report can flexibly modulate how intraparietal sulcus integrates sensory signals into spatial representations to guide behavioral responses (e.g., localization and orienting).}

{Vehicle simulation is an important instrument for the acquisition and maintenance of complex skills (e.g., aircraft handling; Salas, Bowers \& Rhodenizer, 1998). Such training not only improves control performance (i.e., error- or time-based measures), but also alters gaze strategies (Gegenfurtner, Lehtinen \& S\"alj\"o, 2011). It is claimed that eye movements can reflect the strategic allocation of attention (Hornof \& Halverson, 2003). For example, experts exhibit more consistent gaze pattern than novices (Kasarskis et al., 2001). More importantly, flight training can reduce initial differences in gaze patterns between expert and novice pilots (Harris, Glover \& Spady, 1986). Thus, training modulates gaze strategies such that eye movements get more appropriate for the goals of vehicle handling. Unfortunately, training simulations often deviate from the real world, such as available field-of-view (FOV) (Moroney \& Lilienthal, 2008). FOV conditions can influence eye-head coordination during visuo-manual tracking tasks (Sandor \& Leger, 1991). Hence, we ask: Do gaze strategies acquired under reduced FOV conditions, as it might be the case in simulator settings, persist when FOV restrictions are removed? To answer this question, we recorded the eye movements of participants (N\textequals24) who performed a lateral translational movement in 3D space with a simplified rotorcraft, using a head-mounted eye-tracking system (SMI ETG, Sensorimotoric Instruments GmbH; sampling rate: 30 Hz). The experiment took place in a front-projection CAVE environment which enables large FOV. The environment consisted of an airfield with a lateral arrangement of vertical poles that indicated the ideal altitude as well the operator\textquoterights desired path trajectory (see Figure 1). Moreover, points on the ground explicitly indicated the desired path between the start- and end-zone. In a between-subject design, three participant groups received 30 training trials under three different levels of FOV restriction. Subsequently, they were equally tested over ten trials with a full FOV condition (230\mbox{$^\circ$} x 125\mbox{$^\circ$} visual angle). Critically, training conditions differed in terms of the amount of information that was available during flight. Participants who were trained under FOVsmall (60\mbox{$^\circ$} x 60\mbox{$^\circ$} visual angle) could only look two rods ahead without being able to see the ground. FOVvert (180\mbox{$^\circ$} x 60\mbox{$^\circ$} visual angle) allowed the operators to look ahead with regards to the vertical markers but not to see the ground path. FOVlarge (180\mbox{$^\circ$} x 180\mbox{$^\circ$} visual angle) allowed the operators to look ahead with regards to the vertical and ground markers. Leftwards and rightwards lateral movements were performed equally often. To compare the effects of FOV restriction on gaze strategies, only the final FOVfull condition was analyzed. If eye movements are generic, groups should not differ in gaze strategies under FOVfull as gaze pattern should not depend on FOV condition during training. However, gaze patterns during testing should differ if training FOVs have an influence on gaze strategies that persist even with the availability of a larger FOV. We defined four region of interests (ROI) that comprised the areas spanned by the poles that are visible in the FOVsmall training condition (poles near), the area between poles that lie outside of the FOVsmall (poles far), an area spanned by the ground markers which are less than two poles away (ground near) as well as the area between ground markers which are more than two poles away (ground far). We employed linear mixed-effects models (Krueger \& Tian, 2004) for each ROI to test for differences between FOV conditions during training in the number of dwells and the average dwell duration, respectively. For each ROI, we formulated multiple models using RStudio. The full model contained fixed effects for trials (i.e. time) and FOV training condition, an interaction effect between trials and FOV training condition, and random slopes and intercepts for participants and flight direction. Two more parsimonious models differed from the full model only with respect to the interaction effect (model 1) and the interaction effect as well as the fixed effect for FOV training condition (model 2). We conducted Likelihood-Ratio tests (full model vs. model 1 and model 1 vs. model 2) for each ROI to test for significance of the interaction effect and the main effect of FOV training condition, respectively. Figure 2 shows that the FOV condition during training influenced gaze pattern during testing (FOVfull). Reliance on visual cues was influenced by available FOV size during training, whereby smaller FOV sizes resulted in a stronger reliance on proximal cues (near poles and near ground) and larger FOV sizes promoted the use of distant cues (far poles and far ground; see Figure 2a). Participants who received training under FOVsmall condition spent a significantly larger amount of dwells on proximal poles than the FOVlarge group did ($\chi$2(2) \textequals 8.82, p \textless .05). The trend in proportion of dwells on round near reflected the same tendency but was not significant ($\chi$2(2) \textequals 2.26, p \textequals .32). In contrast, larger FOVs during training resulted in participants who relied on distant cues. However, this tendency was not significant for far poles ($\chi$2(2) \textequals 0.37, p \textequals .83) or far ground ($\chi$2(2) \textequals 1.85, p \textequals .40). There was no significant interaction effect for any of the ROIs (all p \textgreater .1). Thus, participants did not vary their gaze strategies during the test trials. Next, we analyzed the effect of FOV size during training on dwell duration. Results for dwell time showed a significant difference in the dwell time on near poles ($\chi$2(2) \textequals12.12, p \textless .01), with FOVlarge leading to a significantly lower dwell time on near poles (see Figure 2b). There were no other significant effects of FOV during training nor any significant interaction effect (all p \textgreater .1). To summarize, FOV conditions shape gaze patterns that stay stable even when FOV conditions change. These findings underscore the relevance of naturalistic simulation conditions during training, especially in terms of FOV. As eye tracking has been shown to be a sensitive marker of pilot\textquoterights situation awareness and attention allocation (Sarter, Mumaw \& Wickens, 2007; Hanson, 2004), these new insights might have important implications for both, the design of training devices and the assessment of training efficiency.}

{Purpose The aim of this project was to implement an ultra-high field (UHF) optimized double inversion recovery (DIR) sequence for gray matter (GM) imaging, enabling whole brain coverage in short acquisition times ( math formula5 min, image resolution 1 mm3). Methods A 3D variable flip angle DIR turbo spin echo (TSE) sequence was optimized for UHF application. We implemented an improved, fast, and specific absorption rate (SAR) efficient TSE imaging module, utilizing improved reordering. The DIR preparation was tailored to UHF application. Additionally, fat artifacts were minimized by employing water excitation instead of fat saturation. Results GM images, covering the whole brain, were acquired in 7 min scan time at 1 mm isotropic resolution. SAR issues were overcome by using a dedicated flip angle calculation considering SAR and SNR efficiency. Furthermore, UHF related artifacts were minimized. Conclusion The suggested sequence is suitable to generate GM images with whole-brain coverage at UHF. Due to the short total acquisition times and overall robustness, this approach can potentially enable DIR application in a routine setting and enhance lesion detection in neurological diseases.}

{In this work we systematically investigate the requirements for successful application of compressed sensing for highly accelerating the acquisition of non-lipid suppressed 1H FID MRSI data at ultra-high fields. It is shown that with a combination of parallel imaging and sparse reconstruction, and an RF coil with an even distribution of receive sensitivity, highly accelerated and high resolution metabolite maps can be acquired at 9.4T through compressed sensing.}

{Introduction Ultralow-field (ULF) nuclear magnetic resonance (NMR) is a promising spectroscopy method allowing for, e.g., the simultaneous detection of multiple nuclei. To overcome the low signal-to-noise ratio that usually hampers a wider application, we present an alternative approach to prepolarized ULF NMR employing hyperpolarization techniques like signal amplification by reversible exchange (SABRE) or Overhauser dynamic nuclear polarization (ODNP). Both techniques allow continuous hyperpolarization of 1H as well as other MR-active nuclei. Methods To be able to measure 1H and 19F simultaneously, a superconducting quantum interference device (SQUID)-based ULF NMR/MRI detection unit was constructed (see fig. 1). Due to the very low intrinsic noise level, SQUIDs are superior to conventional Faraday detection coils at ultralow-fields. Additionally, the broad band characteristics of SQUIDs enable them to simultaneously detect the MR signal of different nuclei such as 13C, 19F or 1H. Since SQUIDs detect the MR signal directly, they are an ideal tool for a quantitative investigation of hyperpolarization techniques such as SABRE or ODNP. Results/Discussion Using SABRE we successfully hyperpolarized fluorinated pyridine derivatives and quantitatively characterized the dependency of the magnetization transfer reaction from parahydrogen, which bonds to an iridium complex as well as to the 1H and 19F nuclei of an exchangeable ligand, as a function of hyperpolarization time and magnetic field strength [1]. Spectra (see fig. 2) and images of the samples were acquired. With ODNP we were able to measure the coupling constant of solutions containing free radicals. Enhancement factors of over 100 were reached in in situ experiments. First proof-of-principle ex vivo images of rats using ODNP enhanced, SQUID based ULF-MRI have been acquired successfully. Conclusions We successfully built a SQUID-based ULF NMR/MRI system to quantitatively investigate the hyperpolarization techniques SABRE and ODNP.}

{How effectively does the brain encode information across large numbers of neurons? Many models predict that shared variability (or, noise correlations) will cause information to saturate for even moderately sized population, although empirical evidence in this regime is severely lacking. We studied this prediction using a novel 3D high-speed in vivo two-photon microscope to record nearly all of the hundreds of neurons in a small volume of the mouse primary visual cortex. We presented full field grating with five closely spaced orientations and measured how encoded information grows with population size. Contrary to numerous predictions, we find that information continues to increase for population sizes of several hundred neurons with little sign of saturation. In addition, a decoder ignoring correlations between neurons can still decode the majority of the information in the population. The growth of information with population size is well described by an equation motivated by models of information limiting correlations [1], I(n) \textequals Ion/ (1+en), with e a consistently low value across numerous anesthetized and awake animals, demonstrating that the magnitude of information-limiting correlations is quite small. Finally, we find the empiric correlation structure is consistent with numerous eigenvectors weakly aligned to the population tuning, f\.{}(j), which can give rise to similar growth. Our results suggest that sensory neural populations represent information in a truly distributed manner and pooling of neural activity within local circuits may be much more eଏective than previously anticipated. The representation in early sensory areas does not appear to be impaired substantially by shared sensory noise.}

{Purpose: CEST allows for indirect detection of diluted molecules via their saturation transfer to the abundant water pool 1\textendash3. At 3T, the frequency separation of different CEST effects is difficult and many applications of CEST use MTRasym evaluation. In this study, we use low-power saturation to separate the two major contributors the MTRasym signal, namely APT (at +3.5 ppm) and NOE effects (at \textendash3.5 ppm), and investigate correlations with 18F-FET PET enhancement in brain tumors. Methods: 9 patients scanned on a 3T PET/MR system for suspected glioma or recurrent glioma were evaluated (1 radio-necrosis, 1 gliosis, 3 high grade, 4 low grade). Selective protein CEST Z-spectra were acquired with 4s saturation (100 Gaussian pulses, B1 \textequals 0.6 $\mu$T, pulse duration 20ms, duty cycle 50\textpercent) at 53 frequency offsets ranging from \textendash100 ppm to +100 ppm. CEST Z-spectra were de-noised using principle component analysis, retaining 15 principle components. Two-stage Lorentzian analysis was applied to estimate contributions from direct water saturation, magnetization transfer effects from macromolecules4, and selective CEST effects. Results: Selective NOE effects were stronger than APT CEST effects in both healthy and diseased tissues. Compared to contralateral tissues, tumor regions exhibit reduced NOE signals and mixed APT signals, consistent with results from previous studies 4,5. There was no correlation between PET uptake and CEST signals within the tumor. Conclusion: NOE and amide CEST separation is possible at 3T and provide additional information compared to 18F-FET PET.}

{Purpose Clinical use of magnetic resonance electrical impedance tomography (MREIT) still requires significant sensitivity improvements. Here, the measurement of the current-induced magnetic field ($\Delta$Bz,c) is improved using systematic efficiency analyses and optimization of multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID) sequences. Theory and Methods Considering T1, T2, and math formula relaxation in the signal-to-noise ratios (SNRs) of the MR magnitude images, the efficiency of MESE and SSFP-FID MREIT experiments, and its dependence on the sequence parameters, are analytically analyzed and simulated. The theoretical results are experimentally validated in a saline-filled homogenous spherical phantom with relaxation parameters similar to brain tissue. Measurement of $\Delta$Bz,c is also performed in a cylindrical phantom with saline and chicken meat. Results The efficiency simulations and experimental results are in good agreement. When using optimal parameters, $\Delta$Bz,c can be reliably measured in the phantom even at injected current strengths of 1 mA or lower for both sequence types. The importance of using proper crusher gradient selection on the phase evolution in a MESE experiment is also demonstrated. Conclusion The efficiencies observed with the optimized sequence parameters will likely render in-vivo human brain MREIT feasible.}

{Glutamate related metabolism can be measured considering the 13C labeling effects from an administered 13C labeled substrate in 1H MR spectra without 13C channels. The advantage of this technique is that some challenges of 13C MRS like non-standard hardware modifications etc. are avoided and the simultaneous observation of 12C- and 13 C-coupled protons is possible. On the other hand the latter also complicates the spectra. In this work, different sequences will be compared to optimize spectral resolution for glutamate and glutamine at 9.4 T.}

{Glutamate related metabolism can be measured considering the 13C labeling effects from an administered 13C labeled substrate in pure 1H MRS spectra without a 13C channel. In this work, simulated 1H MRS spectra with FID, semi-Laser, and two PRESS sequences have been compared to optimize spectral resolution for glutamate and glutamine measurements at 9.4 T. Furthermore, spectral changes according to a two-compartment model were analyzed. As a result, this work indicates the fastest possible acquisition can be obtained with an FID sequence, while the best resolution possible can be obtained with a PRESS sequence.}

{Rapid variable-flip-angle T1 mapping techniques are frequently applied in clinical settings, but their accuracy is often impaired by incomplete spoiling or flip angle miscalibrations. To eliminate these two error sources simultaneously, a combined B1 and T1 mapping method is proposed based on spiral 2D multislice spoiled gradient echo imaging with high spoiling efficiency. The transition to steady state is minimized by an optimized single preparation pulse. A single-shot spiral readout during the preparation module enables ultrafast B1 mapping and as a result reproducible bias-free T1 mapping with whole-brain coverage at clinically relevant resolution in less than one minute.}