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To present electromagnetic simulation setups for detailed analyses of respiration's impact onmml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:semanticsmml:mrowmml:msubsupmml:miB/mml:mimml:mn1/mml:mnmml:mo+/mml:mo/mml:msubsup/mml:mrowmml:annotation$$ {B}_1^{+} $$/mml:annotation/mml:semantics/mml:mathand E-fields, local specific absorption rate (SAR) and associated safety-limits for 7T cardiac imaging.Finite-difference time-domain electromagnetic field simulations were performed at five respiratory states using a breathing body model and a 16-element 7T body transceiver RF-coil array.mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:semanticsmml:mrowmml:msubsupmml:miB/mml:mimml:mn1/mml:mnmml:mo+/mml:mo/mml:msubsup/mml:mrowmml:annotation$$ {B}_1^{+} $$/mml:annotation/mml:semantics/mml:mathand SAR are analyzed for fixed and moving coil configurations. SAR variations are investigated using phase/amplitude shimming considering (i) a local SAR-controlled mode (here SAR calculations consider RF amplitudes and phases) and (ii) a channel-wise power-controlled mode (SAR boundary calculation is independent of the channels' phases, only dependent on the channels' maximum amplitude).Respiration-induced variations of bothmml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:semanticsmml:mrowmml:mrowmml:msubsupmml:miB/mml:mimml:mn1/mml:mnmml:mo+/mml:mo/mml:msubsup/mml:mrow/mml:mrowmml:annotation$$ {B}_1^{+} $$/mml:annotation/mml:semantics/mml:mathamplitude and phase are observed. The flip angle homogeneity depends on the respiratory state used formml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:semanticsmml:mrowmml:mrowmml:msubsupmml:miB/mml:mimml:mn1/mml:mnmml:mo+/mml:mo/mml:msubsup/mml:mrow/mml:mrowmml:annotation$$ {B}_1^{+} $$/mml:annotation/mml:semantics/mml:mathshimming; best results were achieved for shimming on inhale and exhale simultaneously (mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:semanticsmml:mrowmml:mo|/mml:momml:miΔ/mml:mimml:miC/mml:mimml:miV/mml:mimml:mo|/mml:momml:molt;/mml:momml:mn35/mml:mnmml:mo%/mml:mo/mml:mrowmml:annotation$$ \mid \Delta CV\midlt;35\% $$/mml:annotation/mml:semantics/mml:math). The results reflect that respiration impacts position and amplitude of the local SAR maximum. With the local-SAR-control mode, a safety factor of up to 1.4 is needed to accommodate for respiratory variations while the power control mode appears respiration-robust when the coil moves with respiration (SAR peak decrease: 9% exhale→inhale). Instead, a spatially fixed coil setup yields higher SAR variations with respiration.Respiratory motion does not only affect themml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:semanticsmml:mrowmml:msubsupmml:miB/mml:mimml:mn1/mml:mnmml:mo+/mml:mo/mml:msubsup/mml:mrowmml:annotation$$ {B}_1^{+} $$/mml:annotation/mml:semantics/mml:mathdistribution and hence the image contrast, but also location and magnitude of the peak spatial SAR. Therefore, respiration effects may need to be included in safety analyses of RF coils applied to the human thorax.

We investigated whether the impact of tau-pathology on memory performance and on hippocampal/medial temporal memory function in non-demented individuals depends on the presence of amyloid pathology, irrespective of diagnostic clinical stage. We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Two hundred and thirty-five participants completed task functional MRI and provided CSF (92 cognitively unimpaired, 100 experiencing subjective cognitive decline and 43 with mild cognitive impairment). Presence (A+) and absence (A−) of amyloid pathology was defined by CSF amyloid-β42 (Aβ42) levels. Free recall performance in the Free and Cued Selective Reminding Test, scene recognition memory accuracy and hippocampal/medial temporal functional MRI novelty responses to scene images were related to CSF total-tau and phospho-tau levels separately for A+ and A− individuals. We found that total-tau and phospho-tau levels were negatively associated with memory performance in both tasks and with novelty responses in the hippocampus and amygdala, in interaction with Aβ42 levels. Subgroup analyses showed that these relationships were only present in A+ and remained stable when very high levels of tau (>700 pg/ml) and phospho-tau (>100 pg/ml) were excluded. These relationships were significant with diagnosis, age, education, sex, assessment site and Aβ42 levels as covariates. They also remained significant after propensity score based matching of phospho-tau levels across A+ and A− groups. After classifying this matched sample for phospho-tau pathology (T−/T+), individuals with A+/T+ were significantly more memory-impaired than A−/T+ despite the fact that both groups had the same amount of phospho-tau pathology. ApoE status (presence of the E4 allele), a known genetic risk factor for Alzheimer’s disease, did not mediate the relationship between tau pathology and hippocampal function and memory performance. Thus, our data show that the presence of amyloid pathology is associated with a linear relationship between tau pathology, hippocampal dysfunction and memory impairment, although the actual severity of amyloid pathology is uncorrelated. Our data therefore indicate that the presence of amyloid pathology provides a permissive state for tau-related hippocampal dysfunction and hippocampus-dependent recognition and recall impairment. This raises the possibility that in the predementia stage of Alzheimer’s disease, removing the negative impact of amyloid pathology could improve memory and hippocampal function even if the amount of tau-pathology in CSF is not changed, whereas reducing increased CSF tau-pathology in amyloid-negative individuals may not proportionally improve memory function.

The association between cerebral blood supply and cognition has been widely discussed in the recent literature. One focus of this discussion has been the anatomical variability of the circle of Willis, with morphological differences being present in more than half of the general population. While previous studies have attempted to classify these differences and explore their contribution to hippocampal blood supply and cognition, results have been controversial. To disentangle these previously inconsistent findings, we introduce Vessel Distance Mapping (VDM) as a novel methodology for evaluating blood supply, which allows for obtaining vessel pattern metrics with respect to the surrounding structures, extending the previously established binary classification into a continuous spectrum. To accomplish this, we manually segmented hippocampal vessels obtained from high-resolution 7T time-of-flight MR angiographic imaging in older adults with and without cerebral small vessel disease, generating vessel distance maps by computing the distances of each voxel to its nearest vessel. Greater values of VDM-metrics, which reflected higher vessel distances, were associated with poorer cognitive outcomes in subjects affected by vascular pathology, while this relation was not observed in healthy controls. Therefore, a mixed contribution of vessel pattern and vessel density is proposed to confer cognitive resilience, consistent with previous research findings. In conclusion, VDM provides a novel platform, based on a statistically robust and quantitative method of vascular mapping, for addressing a variety of clinical research questions.

Purpose To introduce a study design and statistical analysis framework to assess the repeatability, reproducibility, and minimal detectable changes (MDCs) of metabolite concentrations determined by in vivo MRS. Methods An unbalanced nested study design was chosen to acquire in vivo MRS data within different repeatability and reproducibility scenarios. A spin-echo, full-intensity acquired localized (SPECIAL) sequence was employed at 7 T utlizing three different inversion pulses: a hyperbolic secant (HS), a gradient offset independent adiabaticity (GOIA), and a wideband, uniform rate, smooth truncation (WURST) pulse. Metabolite concentrations, Cramer-Rao lower bounds (CRLBs) and coefficients of variation (CVs) were calculated. Both Bland-Altman analysis and a restricted maximum-likelihood estimation (REML) analysis were performed to estimate the different variance contributions of the repeatability and reproducibility of the measured concentration. A Bland-Altmann analysis of the spectral shape was performed to assess the variance of the spectral shape, independent of quantification model influences. Results For the used setup, minimal detectable changes of brain metabolite concentrations were found to be between 0.40 µmol/g and 2.23 µmol/g. CRLBs account for only 16 % to 74 % of the total variance of the metabolite concentrations. The application of gradient-modulated inversion pulses in SPECIAL led to slightly improved repeatability, but overall reproducibility appeared to be limited by differences in positioning, calibration, and other day-to-day variations throughout different sessions. Conclusion A framework is introduced to estimate the precision of metabolite concentrations obtained by MRS in vivo, and the minimal detectable changes for 13 metabolite concentrations measured at 7 T using SPECIAL are obtained.

Journal of neurology 270(2), 1159-1161 (2023). doi:10.1007/s00415-022-11437-9, Published by Steinkopff, [Darmstadt]

Purpose The anatomy of the circle of Willis (CoW), the brain’s main arterial blood supply system, strongly differs between individuals, resulting in highly variable flow fields and intracranial vascularization patterns. To predict subject-specific hemodynamics with high certainty, we propose a data assimilation (DA) approach that merges fully 4D phase-contrast magnetic resonance imaging (PC-MRI) data with a numerical model in the form of computational fluid dynamics (CFD) simulations. Methods To the best of our knowledge, this study is the first to provide a transient state estimate for the three-dimensional velocity field in a subject-specific CoW geometry using DA. High-resolution velocity state estimates are obtained using the local ensemble transform Kalman filter (LETKF). Results Quantitative evaluation shows a considerable reduction (up to 90%) in the uncertainty of the velocity field state estimate after the data assimilation step. Velocity values in vessel areas that are below the resolution of the PC-MRI data (e.g., in posterior communicating arteries) are provided. Furthermore, the uncertainty of the analysis-based wall shear stress distribution is reduced by a factor of 2 for the data assimilation approach when compared to the CFD model alone. Conclusion This study demonstrates the potential of data assimilation to provide detailed information on vascular flow, and to reduce the uncertainty in such estimates by combining various sources of data in a statistically appropriate fashion.

Magnetic resonance imaging (MRI) is a noninvasive technique that provides excellent contrast for soft tissue organs. However, due to the low density of protons and many air-tissue junctions, its application in the lung is limited. Thus, X‑ray-based methods are often used here (with the well-known disadvantages of ionizing radiation).In this review, we discuss pulmonary MRI with hyperpolarized xenon-129 (Xe-MRI). Xe-MRI provides unique valuable insights into lung microstructure and function, including gas exchange with red blood cells-parameters not accessible by any standard clinical methods.By magnetic labelling, i.e. hyperpolarization, the signal from xenon-129 is amplified by up to 100,000 times. In this process, electrons from rubidium are first polarized to 100% using laser light and then transferred to xenon by collisions. Then the hyperpolarized gas is brought to the patient in a bag and inhaled shortly before the MRI scan.Using special programming (sequences) of the MRI, the ventilation, microstructure, or gas exchange of the lungs, can be displayed in 3D. This allows, for example, quantitative visualization of ventilation defects, alveolar size, tissue gas uptake and gas transfer to the blood.Xe-MRI provides unique information about the state of the lung-noninvasively, in vivo and in less than a minute.HINTERGRUND: Die Magnetresonanztomographie (MRT) ist ein nichtinvasives Verfahren mit hervorragendem Weichteilkontrast. Aufgrund der geringen Protonendichte und vielen Luft-Gewebe-Übergängen ist die Anwendung in der Lunge jedoch eingeschränkt, so dass hier häufig röntgenbasierte Methoden eingesetzt werden (mit den bekannten Nachteilen ionisierender Strahlung).In dieser Übersichtsarbeit wird die Lungen-MRT mit hyperpolarisiertem Xenon-129 (Xe-MRT) dargestellt. Die Xe-MRT erlaubt einzigartige wertvolle Einblicke in die Mikrostruktur und Funktion der Lunge, einschließlich des Gasaustauschs mit roten Blutkörperchen – Parameter, die mit klinischen Standardmethoden nicht zugänglich sind.Durch die magnetische Markierung, die Hyperpolarisierung, wird das Signal von Xenon-129 um bis zu 100.000-fach verstärkt. Hierbei werden die Elektronen von Rubidium mittels Laserlicht zunächst auf 100 % polarisiert und dann durch Stöße auf Xenon übertragen. Danach wird das hyperpolarisierte Gas in einem Beutel zum Patienten gebracht und eingeatmet, kurz bevor die MRT-Aufnahmen beginnen.Durch spezielle Programmierungen (Sequenzen) in der MRT kann die Ventilation, Mikrostruktur oder der Gasaustausch der Lunge in 3‑D dargestellt werden. Dies ermöglicht z. B. die quantitative Darstellung von Belüftungsdefekten, der Größe der Alveolen, der Gasaufnahme im Gewebe und des Gastransfers ins Blut.Die Xe-MRT liefert einzigartige Informationen über den Zustand der Lunge – nichtinvasiv, in vivo und in weniger als einer Minute.

Expert interpretation of anatomical images of the human brain is the central part of neuro-radiology. Several machine learning-based techniques have been proposed to assist in the analysis process. However, the ML models typically need to be trained to perform a specific task, e.g., brain tumour segmentation or classification. Not only do the corresponding training data require laborious manual annotations, but a wide variety of abnormalities can be present in a human brain MRI - even more than one simultaneously, which renders representation of all possible anomalies very challenging. Hence, a possible solution is an unsupervised anomaly detection (UAD) system that can learn a data distribution from an unlabelled dataset of healthy subjects and then be applied to detect out of distribution samples. Such a technique can then be used to detect anomalies - lesions or abnormalities, for example, brain tumours, without explicitly training the model for that specific pathology. Several Variational Autoencoder (VAE) based techniques have been proposed in the past for this task. Even though they perform very well on controlled artificially simulated anomalies, many of them perform poorly while detecting anomalies in clinical data. This research proposes a compact version of the "context-encoding" VAE (ceVAE) model, combined with pre and post-processing steps, creating a UAD pipeline (StRegA), which is more robust on clinical data, and shows its applicability in detecting anomalies such as tumours in brain MRIs. The proposed pipeline achieved a Dice score of 0.642$\pm$0.101 while detecting tumours in T2w images of the BraTS dataset and 0.859$\pm$0.112 while detecting artificially induced anomalies, while the best performing baseline achieved 0.522$\pm$0.135 and 0.783$\pm$0.111, respectively.

PURPOSE: Severe geometric distortions induced by tissue susceptibility, water-fat chemical shift, and eddy currents pose a substantial obstacle in single-shot EPI, especially for high-resolution imaging at ultrahigh field. View angle tilting (VAT)-EPI can mitigate in-plane distortion. However, the accompanied strong image blurring prevented its widespread applications. On the other hand, point-spread function mapping (PSF)-EPI can correct distortion and blurring accurately but requires prolonged scan time. We present fused VAT-PSF-EPI and possibilities for acceleration. METHODS: MR signal equations were explicitly derived to quantify image blurring in VAT-EPI and the maximum acceleration capacity in VAT-PSF-EPI. To validate the theoretical prediction, phantom measurements with varying in-plane parallel imaging factors, slice thicknesses, and RF pulses were conducted at 7 Tesla. In addition, in vivo human brain scans were acquired with T2 and diffusion weighting to assess distortion and blurring correction. RESULTS: VAT can effectively suppress distortion, and the introduced image blurring is corrected through PSF encoding. Up to fourfold acceleration (only 5 shots) in VAT-PSF-EPI was achieved compared with standard PSF-EPI without VAT. VAT-induced signal loss was mitigated by adjusting the sequence parameters and EPI resolution. In vivo T2 -weighted EPI data with 1.4 mm3 resolution demonstrate immunity to water-fat chemical shift-induced distortion. Very high-spatial resolution diffusion-weighted EPI (0.7 × 0.7 × 2.8 mm3 and 1.2 mm3 ) demonstrates the immunity to eddy current-induced distortion. CONCLUSION: VAT-PSF-EPI is a novel spin-echo EPI-based sequence for fast high-resolution diffusion imaging at ultrahigh field.

RF absorption in patients undergoing MRI procedures poses a major safety risk due to resulting heating in the tissue. In order to stay below permitted temperature limits the SAR has to be quantified and limited. Based on the model of an infant inside a birdcage coil we have investigated the SAR distribution in the body at 1.5T. Thermal simulations could thus be performed to establish a relationship between the limitations of SAR and temperature. Results show a thermal hotspot in the neck region caused by high local absorption. The temperature limits in this local area were exceeded after 7min of excitation within regulatory SAR limits. For a long-term exposure critical organs in the body's core also undergo thermal stress beyond limitations. This indicates the need for constraints in regard to long MR procedures to consider the temporal aspect of heating.Clinical Relevance-This work establishes a relationship between SAR and temperature in infants undergoing MRI and shows potential risks of long-term procedures due to induced thermal stress.

Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA.The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.We used magnetic resonance imaging to acquire T1-weighted images and diffusion tensor images from 12 MSA-C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel-based-morphometry, tract-based spatial statistics, and tractography-based regional diffusion tensor images analysis.Whole-brain and cerebellar-focused voxel-based-morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA-C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA-C patients. The tract-based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA-C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography-based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA-C, but not SAOA.Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA-C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA-C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Ultra-high-field (UHF) magnetic resonance (MR) scanners, that is, equipment operating at static magnetic field of 7 tesla (7 T) and above, enable the acquisition of data with greatly improved signal-to-noise ratio with respect to conventional MR systems (e.g., scanners operating at 1.5 T and 3 T). The change in tissue relaxation times at UHF offers the opportunity to improve tissue contrast and depict features that were previously inaccessible. These potential advantages come, however, at a cost: in the majority of UHF-MR clinical protocols, potential drawbacks may include signal inhomogeneity, geometrical distortions, artifacts introduced by patient respiration, cardiac cycle, and motion. This article reviews the 7 T MR literature reporting the recent studies on the most widespread neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.

Dynamic imaging is a beneficial tool for interventions to assess physiological changes. Nonetheless during dynamic MRI, while achieving a high temporal resolution, the spatial resolution is compromised. To overcome this spatio-temporal trade-off, this research presents a super-resolution (SR) MRI reconstruction with prior knowledge based fine-tuning to maximise spatial information while reducing the required scan-time for dynamic MRIs. An U-Net based network with perceptual loss is trained on a benchmark dataset and fine-tuned using one subject-specific static high resolution MRI as prior knowledge to obtain high resolution dynamic images during the inference stage. 3D dynamic data for three subjects were acquired with different parameters to test the generalisation capabilities of the network. The method was tested for different levels of in-plane undersampling for dynamic MRI. The reconstructed dynamic SR results after fine-tuning showed higher similarity with the high resolution ground-truth, while quantitatively achieving statistically significant improvement. The average SSIM of the lowest resolution experimented during this research (6.25~\% of the k-space) before and after fine-tuning were 0.939 $\pm$ 0.008 and 0.957 $\pm$ 0.006 respectively. This could theoretically result in an acceleration factor of 16, which can potentially be acquired in less than half a second. The proposed approach shows that the super-resolution MRI reconstruction with prior-information can alleviate the spatio-temporal trade-off in dynamic MRI, even for high acceleration factors.

Segmentation of abdominal organs has been a comprehensive, yet unresolved, research field for many years. In the last decade, intensive developments in deep learning (DL) introduced new state-of-the-art segmentation systems. Despite outperforming the overall accuracy of existing systems, the effects of DL model properties and parameters on the performance are hard to interpret. This makes comparative analysis a necessary tool towards interpretable studies and systems. Moreover, the performance of DL for emerging learning approaches such as cross-modality and multi-modal semantic segmentation tasks has been rarely discussed. In order to expand the knowledge on these topics, the CHAOS – Combined (CT-MR) Healthy Abdominal Organ Segmentation challenge was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI), 2019, in Venice, Italy. Abdominal organ segmentation from routine acquisitions plays an important role in several clinical applications, such as pre-surgical planning or morphological and volumetric follow-ups for various diseases. These applications require a certain level of performance on a diverse set of metrics such as maximum symmetric surface distance (MSSD) to determine surgical error-margin or overlap errors for tracking size and shape differences. Previous abdomen related challenges are mainly focused on tumor/lesion detection and/or classification with a single modality. Conversely, CHAOS provides both abdominal CT and MR data from healthy subjects for single and multiple abdominal organ segmentation. Five different but complementary tasks were designed to analyze the capabilities of participating approaches from multiple perspectives. The results were investigated thoroughly, compared with manual annotations and interactive methods. The analysis shows that the performance of DL models for single modality (CT / MR) can show reliable volumetric analysis performance (DICE: 0.98 ± 0.00 / 0.95 ± 0.01), but the best MSSD performance remains limited (21.89 ± 13.94 / 20.85 ± 10.63 mm). The performances of participating models decrease dramatically for cross-modality tasks both for the liver (DICE: 0.88 ± 0.15 MSSD: 36.33 ± 21.97 mm). Despite contrary examples on different applications, multi-tasking DL models designed to segment all organs are observed to perform worse compared to organ-specific ones (performance drop around 5%). Nevertheless, some of the successful models show better performance with their multi-organ versions. We conclude that the exploration of those pros and cons in both single vs multi-organ and cross-modality segmentations is poised to have an impact on further research for developing effective algorithms that would support real-world clinical applications. Finally, having more than 1500 participants and receiving more than 550 submissions, another important contribution of this study is the analysis on shortcomings of challenge organizations such as the effects of multiple submissions and peeking phenomenon. © 2020 Elsevier B.V., 116E133, BIDEB-2214 College of Environmental Science and Forestry, State University of New York, ESF: 1059B191701102, BIDEB-2219, ZS/2016/08/80646 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK, The organizers would like to thank Ivana Isgum and Tom Vercauteren in the challenge committee of ISBI 2019 for their guidance and support. We express our gratitude to supporting organizations of the grand-challenge.org platform. We thank Esranur Kazaz, Umut Baran Ekinci, Ece K?se, Fabian Isensee, David V?lgyes, and Javier Coronel for their contributions. Last but not least, our special thanks go to Ludmila I. Kuncheva for her valuable contributions. This work is supported by Scientific and Technological Research Council of Turkey (TUBITAK) ARDEB-EEEAG under grant number 116E133 and TUBITAK BIDEB-2214 International Doctoral Research Fellowship Programme. The work of P. Ernst, S. Chatterjee, O. Speck and, A. N?rnberger was conducted within the context of the International Graduate School MEMoRIAL at OvGU Magdeburg, Germany, supported by ESF (project no. ZS/2016/08/80646). The work of S. Aslan within the context of Ca? Foscari University of Venice is supported by under TUBITAK BIDEB-2219 grant no 1059B191701102., This work is supported by Scientific and Technological Research Council of Turkey (TUBITAK) ARDEB-EEEAG under grant number 116E133 and TUBITAK BIDEB-2214 International Doctoral Research Fellowship Programme. The work of P. Ernst, S. Chatterjee, O. Speck and, A. Nürnberger was conducted within the context of the International Graduate School MEMoRIAL at OvGU Magdeburg, Germany, supported by ESF (project no. ZS/2016/08/80646). The work of S. Aslan within the context of Ca’ Foscari University of Venice is supported by under TUBITAK BIDEB-2219 grant no 1059B191701102.

Object: This study evaluates inter-site and intra-site reproducibility at ten different 7 T sites for quantitative brain imaging. Material and methods: Two subjects - termed the "traveling heads" - were imaged at ten different 7 T sites with a harmonized quantitative brain MR imaging protocol. In conjunction with the system calibration, MP2RAGE, QSM, CEST and multi-parametric mapping/relaxometry were examined. Results: Quantitative measurements with MP2RAGE showed very high reproducibility across sites and subjects, and errors were in concordance with previous results and other field strengths. QSM had high inter-site reproducibility for relevant subcortical volumes. CEST imaging revealed systematic differences between the sites, but reproducibility was comparable to results in the literature. Relaxometry had also very high agreement between sites, but due to the high sensitivity, differences caused by different applications of the B1 calibration of the two RF coil types used were observed. Conclusion: Our results show that quantitative brain imaging can be performed with high reproducibility at 7 T and with similar reliability as found at 3 T for multicenter studies of the supratentorial brain.

PURPOSE: Quantitative assessment of prospective motion correction (PMC) capability at 7T MRI for compliant healthy subjects to improve high-resolution images in the absence of intentional motion. METHODS: Twenty-one healthy subjects were imaged at 7 T. They were asked not to move, to consider only unintentional motion. An in-bore optical tracking system was used to monitor head motion and consequently update the imaging volume. For all subjects, high-resolution T1 (3D-MPRAGE), T2 (2D turbo spin echo), proton density (2D turbo spin echo), and T∗2 (2D gradient echo) weighted images were acquired with and without PMC. The images were evaluated through subjective and objective analysis. RESULTS: Subjective evaluation overall has shown a statistically significant improvement (5.5%) in terms of image quality with PMC ON. In a separate evaluation of every contrast, three of the four contrasts (T1 , T2 , and proton density) have shown a statistically significant improvement (9.62%, 9.85%, and 9.26%), whereas the fourth one ( T∗2) has shown improvement, although not statistically significant. In the evaluation with objective metrics, average edge strength has shown an overall improvement of 6% with PMC ON, which was statistically significant; and gradient entropy has shown an overall improvement of 2%, which did not reach statistical significance. CONCLUSION: Based on subjective assessment, PMC improved image quality in high-resolution images of healthy compliant subjects in the absence of intentional motion for all contrasts except T∗2, in which no significant differences were observed. Quantitative metrics showed an overall trend for an improvement with PMC, but not all differences were significant.

Here, we present an extension to our previously published structural ultrahigh resolution T1-weighted magnetic resonance imaging (MRI) dataset with an isotropic resolution of 250 µm, consisting of multiple additional ultrahigh resolution contrasts. Included are up to 150 µm Time-of-Flight angiography, an updated 250 µm structural T1-weighted reconstruction, 330 µm quantitative susceptibility mapping, up to 450 µm structural T2-weighted imaging, 700 µm T1-weighted back-to-back scans, 800 µm diffusion tensor imaging, one hour continuous resting-state functional MRI with an isotropic spatial resolution of 1.8 mm as well as more than 120 other structural T1-weighted volumes together with multiple corresponding proton density weighted acquisitions collected over ten years. All data are from the same participant and were acquired on the same 7 T scanner. The repository contains the unprocessed data as well as (pre-)processing results. The data were acquired in multiple studies with individual goals. This is a unique and comprehensive collection comprising a “human phantom” dataset. Therefore, we compiled, processed, and structured the data, making them publicly available for further investigation., Measurement(s) Diffusion Weighted Imaging • Magnetization-Prepared Rapid Gradient Echo MRI • Functional Magnetic Resonance Imaging • T2 (Observed)-Weighted Imaging • Gradient Echo MRI • MR Imaging Acquisition Protocol Element Time of Flight Contrast Indicator Technology Type(s) 7 Tesla Magnetic Resonance Imaging Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.14095997

ObjectiveCerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein.Methods7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein.ResultsA total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%).ConclusionOur findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.

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 (≥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.

The aim of this study was to compare the assessment of low-grade meniscal tears and cartilage damage in ultrahigh-field magnetic resonance imaging (MRI) at 7 T to routine clinical MRI at 3 T.This study was approved by the local ethics committee, and written informed consent was obtained from each patient. Forty-one patients with suspected meniscal damage or mild osteoarthritis (Kellgren-Lawrence score, 0-2) received 7 T as well as routine clinical 3 T consecutively. The imaging protocol at both field strengths consisted of PD-weighted imaging with more than doubled resolution at 7 T. Images were read blinded regarding field strength and patient characteristics by 3 readers with different experience in musculoskeletal MRI (3 years, 6 years, and 10 years) according to a modified whole-organ MRI score of the knee in osteoarthritis and the Score of the International Cartilage Repair Society. Arthroscopic reports as a criterion standard were available for 12 patients. A multifactorial mixed model analysis was performed.The mean cumulated diagnostic score at 7 T was significantly closer to the criterion standard compared with 3 T in patients where criterion standard was available (P0.001). In all 41 patients, the damages were rated more severely at 7 T reflected by a mean higher cumulative score in cartilage (P0.001) and in the meniscus (P0.001). No difference in interreader variability between 3 T and 7 T was observed. Imaging acquisition time was nearly identical.Morphologic imaging of cartilage and meniscal damage of the knee in ultrahigh-field MRI at 7 T with PD-weighted TSE sequences seemed to have a significantly higher diagnostic accuracy than 3 T and can be performed with equal acquisition times while exploiting higher resolution of 7 T.

In a dynamic world, it is essential to decide when to leave an exploited resource. Such patch-leaving decisions involve balancing the cost of moving against the gain expected from the alternative patch. This contrasts with value-guided decisions that typically involve maximizing reward by selecting the current best option. Patterns of neuronal activity pertaining to patch-leaving decisions have been reported in dorsal anterior cingulate cortex (dACC), whereas competition via mutual inhibition in ventromedial prefrontal cortex (vmPFC) is thought to underlie value-guided choice. Here, we show that the balance between cortical excitation and inhibition (E/I balance), measured by the ratio of GABA and glutamate concentrations, plays a dissociable role for the two kinds of decisions. Patch-leaving decision behaviour relates to E/I balance in dACC. In contrast, value-guided decision-making relates to E/I balance in vmPFC. These results support mechanistic accounts of value-guided choice and provide evidence for a role of dACC E/I balance in patch-leaving decisions.

Background and purpose The evaluation of a suspected malfunction of a ventricular shunt is a common procedure in neurosurgery. The evaluation relies on either the interpretation of the ventricular width using cranial imaging or invasive techniques. Several attempts have been made to measure the flow velocity of cerebrospinal fluid (CSF) utilizing different phase-contrast magnet resonance imaging (PC MRI) techniques. In the present study, we evaluated 3 T (Tesla) MRI scanners for their effectiveness in determining of flow in the parenchymal portion of ventricular shunt systems with adjustable valves containing magnets. Methods At first, an MRI phantom was used to measure the phase-contrasts at different constant low flow rates. The next step was to measure the CSF flow in patients treated with ventricular shunts without suspected malfunction of the shunt under observation. Results The measurements of the phantom showed a linear correlation between the CSF flow and corresponding phase values. Despite many artifacts resulting from the magnetic valves, the ventricular catheter within the parenchymal portion of shunt was not superimposed by artifacts at each PC MRI plane and clearly distinguishable in 9 of 12 patients. Three patients suffering from obstructive hydrocephalus showed a clear flow signal. Conclusion CSF flow detected within the parenchymal portion of the shunt by PC MRI may reliably provide information about the functional status of a ventricular shunt. Even in patients whose hydrocephalus was treated with magnetic adjustable valves, the CSF flow was detectable using PC MRI sequences at 3 T field strength.

Medial temporal lobe dependent cognitive functions are highly vulnerable to hypoxia in the hippocampal region, yet little is known about the relationship between the richness of hippocampal vascular supply and cognition. Hippocampal vascularization patterns have been categorized into a mixed supply from both the posterior cerebral artery and the anterior choroidal artery or a single supply by the posterior cerebral artery only. Hippocampal arteries are small and affected by pathological changes when cerebral small vessel disease is present. We hypothesized, that hippocampal vascularization patterns may be important trait markers for vascular reserve and modulate (i) cognitive performance; (ii) structural hippocampal integrity; and (iii) the effect of cerebral small vessel disease on cognition. Using high-resolution 7 T time-of-flight angiography we manually classified hippocampal vascularization patterns in older adults with and without cerebral small vessel disease in vivo. The presence of a mixed supplied hippocampus was an advantage in several cognitive domains, including verbal list learning and global cognition. A mixed supplied hippocampus also was an advantage for verbal memory performance in cerebral small vessel disease. Voxel-based morphometry showed higher anterior hippocampal grey matter volume in mixed, compared to single supply. We discuss that a mixed hippocampal supply, as opposed to a single one, may increase the reliability of hippocampal blood supply and thereby provide a hippocampal vascular reserve that protects against cognitive impairment.

PURPOSE: To compare motion tracking by two modern methods (fat navigators - FatNavs and Moiré phase tracking - MPT) as well as their performance for retrospective correction of very high resolution acquisitions. METHODS: A direct comparison of FatNavs and MPT motion parameters was performed for several deliberate motion patterns to estimate the agreement between methods. In addition, two different navigator resolution were applied. 0.5 mm isotropic MP2RAGE images with simultaneous MPT and FatNavs tracking were acquired in nine cooperative subjects with no intentional motion. Retrospective motion corrections based on both tracking modalities were compared qualitatively and quantitatively. The FatNavs impact on quantitative T(1) maps was also investigated. RESULTS: Both methods showed good agreement within a 0.3 mm/° margin in subjects that moved very little. Higher resolution FatNavs (2mm) showed overall better agreement with MPT than 4mm resolution ones, except for fast and large motion. The retrospective motion corrections based on MPT or FatNavs were at par in 33 cases out of 36, and visibly improved image quality compared to the uncorrected images. In separate fringe cases, both methods suffered from their respective potential shortcomings: unreliable marker attachment for MPT and poor temporal resolution for FatNavs. The magnetization transfer induced by the navigator RF pulses had a visible impact on the T1 values distribution, with a shift of the gray and white matter peaks of 12 ms at most. CONCLUSION: This work confirms both FatNavs and MPT as excellent retrospective motion correction methods for very high resolution imaging of cooperative subjects.

In Alzheimer's disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNFVal66Met) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNFVal66Met an important modulating factor of cognitive impairment in AD. However, the effect of BDNFVal66Met on functional networks that may underlie cognitive impairment in AD is poorly understood. Using a cross-validation approach, we first explored in subjects with autosomal dominant AD (ADAD) from the Dominantly Inherited Alzheimer Network (DIAN) the effect of BDNFVal66Met on resting-state fMRI assessed functional networks. In seed-based connectivity analysis of six major large-scale networks, we found a stronger decrease of hippocampus (seed) to medial-frontal connectivity in the BDNFVal66Met carriers compared to BDNFVal homozogytes. BDNFVal66Met was not associated with connectivity in any other networks. Next, we tested whether the finding of more pronounced decrease in hippocampal-medial-frontal connectivity in BDNFVal66Met could be also found in elderly subjects with sporadically occurring Aβ, including a group with subjective cognitive decline (N = 149, FACEHBI study) and a group ranging from preclinical to AD dementia (N = 114, DELCODE study). In both of these independently recruited groups, BDNFVal66Met was associated with a stronger effect of more abnormal Aβ-levels (assessed by biofluid-assay or amyloid-PET) on hippocampal-medial-frontal connectivity decreases, controlled for hippocampus volume and other confounds. Lower hippocampal-medial-frontal connectivity was associated with lower global cognitive performance in the DIAN and DELCODE studies. Together these results suggest that BDNFVal66Met is selectively associated with a higher vulnerability of hippocampus-frontal connectivity to primary AD pathology, resulting in greater AD-related cognitive impairment.

OBJECTIVE: This study evaluates the inter-site and intra-site reproducibility of 7 Tesla brain imaging and compares it to literature values for other field strengths.MATERIALS AND METHODS: The same two subjects were imaged at eight different 7 T sites. MP2RAGE, TSE, TOF, SWI, EPI as well as B1 and B0 field maps were analyzed quantitatively to assess inter-site reproducibility. Intra-site reproducibility was measured with rescans at three sites.RESULTS: Quantitative measures of MP2RAGE scans showed high agreement. Inter-site and intra-site reproducibility errors were comparable to 1.5 and 3 T. Other sequences also showed high reproducibility between the sites, but differences were also revealed. The different RF coils used were the main source for systematic differences between the sites.CONCLUSION: Our results show for the first time that multi-center brain imaging studies of the supratentorial brain can be performed at 7 T with high reproducibility and similar reliability as at 3T. This study develops the basis for future large-scale 7 T multi-site studies.

Item does not contain fulltext The habenula is a pivotal structure in the neural network that implements various forms of cognitive and motivational functions and behaviors. Moreover, it has been suggested to be part of the brain's circadian system, not at least because habenular neurons are responsive to retinal illumination and exhibit circadian modulations of their firing patterns in animal research. However, no study has directly investigated the human habenula in this regard. We developed a paradigm in which alternating phases of high and low luminance are used to study human habenular functioning. In two experiments with independent samples, fMRI data of 24 healthy participants were acquired at a field strength of 7T, and of 21 healthy participants at 3T. Region of interest analyses revealed that the human habenula is responsive to light as well, resulting in a decrease in activation when a change in luminance occurs. Although this pattern is not predicted by animal research, we were able to replicate this finding in a second independent data set. Furthermore, we demonstrate that the strength of decrease in activation is modulated in a circadian fashion, being more strongly deactivated in morning than in afternoon sessions. Taken together, these findings provide strong evidence that changes in illumination elicit changes in habenular activation and that these changes appear to be more pronounced in the morning than in the afternoon. 8 p.

Considerable evidence suggests a close relationship between vascular and degenerative pathology in the human hippocampus. Due to the intrinsic fragility of its vascular network, the hippocampus appears less able to cope with hypoperfusion and anoxia than other cortical areas. Although hippocampal blood supply is generally provided by the collateral branches of the posterior cerebral artery (PCA) and the anterior choroidal artery (AChA), different vascularization patterns have been detected postmortem. To date, a methodology that enables the classification of individual hippocampal vascularization patterns in vivo has not been established. In this study, using high-resolution 7 Tesla time-of-flight angiography data (0.3 mm isotropic resolution) in young adults, we classified individual variability in hippocampal vascularization patterns involved in medial temporal lobe blood supply in vivo. A strong concordance between our classification and previous autopsy findings was found, along with interesting anatomical observations, such as the variable contribution of the AChA to hippocampal supply, the relationships between hippocampal and PCA patterns, and the different distribution patterns of the right and left hemispheres. The approach presented here for determining hippocampal vascularization patterns in vivo may provide new insights into not only the vulnerability of the hippocampus to vascular and neurodegenerative diseases but also hippocampal vascular plasticity after exercise training., Highlights • First attempt to classify human hippocampal vascularization in vivo using 7Tesla Angiography • Good concordance between in vivo findings and autopsy studies • A new avenue to investigate interindividual variability in hippocampal vascular plasticity • A new avenue for linking individual vascular anatomical phenotypes to neurodegenerative and vascular pathology

The locus coeruleus is the site of the earliest pathological changes in many neurodegenerative diseases. Betts et al. describe how in vivo locus coeruleus imaging can be used as a biomarker for noradrenergic dysfunction in neurodegenerative diseases, and outline a strategy for achieving reliable and biologically validated imaging approaches., Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer’s disease, atypical neurodegenerative dementias and Parkinson’s disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

Sporadic adult-onset ataxia of unknown etiology (SAOA) is a non-genetic neurodegenerative disorder of the cerebellum of unknown cause which manifests with progressive ataxia without severe autonomic failure. Although SAOA is associated with cerebellar degeneration, little is known about the specific cerebellar atrophy pattern in SAOA. Thirty-seven SAOA patients and 49 healthy controls (HCs) were included at two centers. We investigated the structural and functional characteristics of SAOA brains using voxel-based morphometry (VBM) and resting-state functional imaging (rs-fMRI). In order to examine the functional consequence of structural cerebellar alterations, the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and then assessed their relation with disease severity, disease duration, and age of onset within these regions. Group differences were investigated using two-sample t tests, controlling for age, gender, site, and the total intracranial volume. The VBM analysis revealed a significant, mostly bilateral reduction of local gray matter (GM) volume in lobules I–V, V, VI, IX, X, and vermis VIII a/b in SAOA patients, compared with HCs. The GM volume loss in these regions was significantly associated with disease severity, disease duration, and age of onset. The disease-related atrophy regions did not show any functional alternations compared with HCs but were functionally characterized by high ALFF and poor DC compared with intact cerebellar regions. Our data revealed volume reduction in SAOA in cerebellar regions that are known to be involved in motor and somatosensory processing, corresponding with the clinical phenotype of SAOA. Our data suggest that the atrophy occurs in those cerebellar regions which are characterized by high ALFF and poor DC. Further studies have to show if these findings are specific for SAOA, and if they can be used to predict disease progression.

Mnemonic discrimination, the ability to distinguish similar events in memory, relies on subregions in the human medial temporal lobes (MTLs). Tau pathology is frequently found within the MTL of older adults and therefore likely to affect mnemonic discrimination, even in healthy older individuals. The MTL subregions that are known to be affected early by tau pathology, the perirhinal-transentorhinal region (area 35) and the anterior-lateral entorhinal cortex (alEC), have recently been implicated in the mnemonic discrimination of objects rather than scenes. Here we used an object-scene mnemonic discrimination task in combination with fMRI recordings and analyzed the relationship between subregional MTL activity, memory performance, and levels of total and phosphorylated tau as well as Aβ42/40 ratio in CSF. We show that activity in alEC was associated with mnemonic discrimination of similar objects but not scenes in male and female cognitively unimpaired older adults. Importantly, CSF tau levels were associated with increased fMRI activity in the hippocampus, and both increased hippocampal activity as well as tau levels were associated with mnemonic discrimination of objects, but again not scenes. This suggests that dysfunction of the alEC-hippocampus object mnemonic discrimination network might be a marker for tau-related cognitive decline.SIGNIFICANCE STATEMENTSubregions in the human medial temporal lobe are critically involved in episodic memory and, at the same time, affected by tau pathology. Impaired object mnemonic discrimination performance as well as aberrant activity within the entorhinal-hippocampal circuitry have been reported in earlier studies involving older individuals, but it has thus far remained elusive whether and how tau pathology is implicated in this specific impairment. Using task-related fMRI in combination with measures of tau pathology in CSF, we show that measures of tau pathology are associated with increased hippocampal activity and reduced mnemonic discrimination of similar objects but not scenes. This suggests that object mnemonic discrimination tasks could be promising markers for tau-related cognitive decline.

Background Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventral anterior cingulate cortex. The glutamine/glutamate (Gln/Glu) ratio was proposed to be connected to glutamatergic cycling, which is hypothesized to be dysregulated in MDD. As an indicator of regional metabolite status, this ratio might be a robust state marker sensitive to clinical heterogeneity. Methods Thirty-two MDD patients (mean age 40.88 ± 13.66 years, 19 women) and control subjects (mean age 33.09 ± 8.24 years, 19 women) were compared for pregenual anterior cingulate cortex levels of Gln/Glu, Gln/total creatine (tCr), Glu/tCr, and gamma-aminobutyric acid/tCr as determined by high-field magnetic resonance spectroscopy. We tested if symptom severity (Hamilton Depression Rating Scale) and anhedonia (Snaith-Hamilton Pleasure Scale) influence the relation of metabolites to clinical symptoms. Results MDD patients showed higher Gln/Glu. This was driven by marginally higher Gln/tCr and nonsignificantly lower Glu/tCr. Groups defined by severity moderated relationship between Gln/Glu and the Hamilton Depression Rating Scale. Moreover, severe cases differed from both control subjects and moderate cases. Groups defined by the Snaith-Hamilton Pleasure Scale also displayed differential relationship between Gln/Glu and levels of anhedonia, predominantly driven by Gln/tCr. Conclusions We elaborate previous accounts of metabolite deficits in the anterior cingulate cortex toward increased Gln/Glu. There is a moderated relationship between severity and the ratio, which suggests consideration of different mechanisms or disease state for the respective subgroups in future studies.

Background Modifying brain activity using non-invasive, low intensity transcranial electrical brain stimulation (TES) has rapidly increased during the past 20 years. Alternating current stimulation (ACS), for example, has been shown to alter brain rhythm activities and modify neuronal functioning in the visual system. Daily application of transorbital ACS to patients with optic nerve damage induces functional connectivity reorganization, and partially restores vision. While ACS is thought to mainly modify neuronal mechanisms, e.g. changes in brain oscillations that can be detected by EEG, it is still an open question, whether and how it may alter BOLD activity. Objective We evaluated whether transorbital ACS modulates BOLD activity in early visual cortex using high-resolution 7 Tesla functional magnetic resonance imaging (fMRI). Methods In this feasibility study transorbital ACS in the alpha range and sham ACS was applied in a random block design in five healthy subjects for 20 min at 1 mA. Brain activation in the visual areas V1, V2 and V3 were measured using 7 Tesla fMRI-based retinotopic mapping at the time points before (baseline) and after stimulation. In addition, we collected data from one hemianopic stroke patient with visual cortex damage after ten daily sessions with 25–50 min stimulation duration. Results In healthy subjects transorbital ACS increased the activated cortical surface area, decreased the fMRI response amplitude and increased coherence in the visual cortex, which was most prominent in the full field task. In the patient, stimulation improved contrast sensitivity in the central visual field. BOLD amplitudes and coherence values were increased in most early visual areas in both hemispheres, with the most pronounced activation detected during eccentricity testing in retinotopic mapping. Conclusions This feasibility study showed that transorbital ACS modifies BOLD activity to visual stimulation, which outlasts the duration of the AC stimulation. This is in line with earlier neurophysiological findings of increased power in EEG recordings and functional connectivity reorganization in patients with impaired vision. Accordingly, the larger BOLD response area after stimulation can be explained by more coherent activation and lower variability in the activation. Alternatively, increased neuronal activity can also be taken into account. Controlled trials are needed to systematically evaluate the potential of repetitive transorbital ACS to improve visual function after visual pathway stroke and to determine the cause-effect relationship between neural and BOLD activity changes.

Purpose Recent literature has shown the potential of high-resolution quantitative susceptibility mapping (QSM) with ultra-high field MRI for imaging the anatomy, the vasculature, and investigating their magnetostatic properties. Higher spatial resolutions, however, translate to longer scans resulting, therefore, in higher vulnerability to, and likelihood of, subject movement. We propose a gradient-recalled echo sequence with prospective motion correction (PMC) to address such limitation. Methods Data from 4 subjects were acquired at 7T. The effect of small and large motion on QSM with and without PMC was assessed qualitatively and quantitatively. Full brain QSM and QSM-based venograms with up to 0.33 mm isotropic voxel size were reconstructed. Results With PMC, motion artifacts in QSM and QSM-based venograms were largely eliminated, enabling-in both large- and small-amplitude motion regimes-accurate depiction of the cortex, vasculature, and other small anatomical structures that are often blurred as a result of head movement or indiscernible at lower image resolutions. Quantitative analyses demonstrated that uncorrected motion could bias regional susceptibility distributions, a trend that was greatly reduced with PMC. Conclusion Qualitatively, PMC prevented image degradation because of motion artifacts, providing highly detailed QSM images and venograms. Quantitatively, PMC increased the reproducibility of susceptibility measures.

Purpose To analyze the interference between a wireless high definition multimedia interface (WHDMI) and magnetic resonance imaging (MRI) image quality at 1.5T, 3T and 7T. Materials and methods A wireless video transmission system (WVTS) consisting of a WHDMI and a projector was used to transmit and display a video stream into the magnet room. MR image quality was analyzed at 1.5T, 3T and 7T. Signal-to-noise-ratio $(\overline {{\rm{SNR}}} )$ and radio frequency (RF)-noise spectrum were measured at three transmitter positions (A: inside the cabin, B: in front of the waveguide and C: in the control room). WVTS system functionality tests included measurements of reliability, delay and image quality. Results With the WVTS mean $\overline {{\rm{SNR}}} $ values significantly decreased in comparison to the reference for all positions and fieldstrenghts, while the spectra’s baseline is elevated at 1.5T and 3T. Peaks related to continuous wave interferences are apparent at all field strenghts. For WHDMI alone mean $\overline {{\rm{SNR}}} $ values were stable without significant differences to the reference. No elevation of the spectra’s baseline could be observed. Functionality measurements confirmed high connection reliability with stable image quality and no delays for all field strengths. Conclusion We conclude that wireless transmission of video streams into the MRI magnet room is feasible at all field strengths without hampering image quality.

The neural basis of reserve capacity in Alzheimer’s disease is yet to be fully determined. Franzmeier et al. show that greater left frontal hub connectivity within the fronto-parietal control network is associated with greater resilience of cognitive performance during the early stages of autosomal dominant and sporadic Alzheimer’s disease., Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer’s disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer’s disease is at least partially attributable to higher left frontal cortex-hub connectivity.

The unique ability of magnetic resonance imaging to measure temperature noninvasively, in vivo, makes it an attractive tool for monitoring interventional procedures, such as radiofrequency or microwave ablation in real-time. The most frequently used approach for magnetic resonance-based temperature measurement is proton resonance frequency (PRF) thermometry. Although it has many advantages, including tissue-independence and real-time capability, the main drawback is its motion sensitivity. This is likely the reason PRF thermometry in moving organs, such as the liver, is not commonly used in the clinical arena. In recent years, however, several developments suggest that motion-corrected thermometry in the liver is achievable. The present article summarizes the diverse attempts to correct thermometry in the liver. Therefore, the physical principle of PRF is introduced, with additional references for necrosis zone estimation and how to deal with fat phase modulation, and main magnetic field drifts. The primary categories of motion correction are presented, including general methods for motion compensation and library-based approaches, and referenceless thermometry and hybrid methods. Practical validation of the described methods in larger patient groups will be necessary to establish accurate motion-corrected thermometry in the clinical arena, with the goal of complete liver tumor ablation.

The aim of this study was the development and evaluation of a real-time guidance support using optical Moiré Phase Tracking (MPT) for magnetic resonance (MR) guided percutaneous interventions. A gradient echo sequence, capable of real-time position updates by the MPT system, was modified to enable needle guidance based on four rigidly attached MPT markers at the back of a needle. Two perpendicular imaging planes were automatically aligned along the calibrated needle and centered at its tip. For user guidance, additional information about the needle trajectory and the tip to target distance were added as image overlay. Both, images and guiding information were displayed on the in-room monitor to facilitate MR guided interventions. The guidance support was evaluated by four experienced interventional radiologists and four novices targeting rubber O-rings embedded in a custom-made phantom on a 3T wide-bore MRI system (80 punctures). The skin to target time, user error, system error and total error were analyzed. The mean skin to target time was 146s±68s with no statistically significant difference between experts and novices. A low mean user error (0.91mm±0.43mm), system error (0.53mm±0.27mm) and total error (0.99mm±0.47mm) was reached in all directions. No statistically significant difference in user error, system error and total error could be found between experts and novices. The presented tracking and image guidance system combined with the user interface offers continuous and interactive control of the imaging plane while puncturing in the magnet enabling accurate real-time feedback for both, experienced and non-experienced users.

Ketamine exerts rapid antidepressant effects peaking 24 h after a single infusion, which have been suggested to be reflected by both reduced functional connectivity (FC) within default mode network (DMN) and altered glutamatergic levels in the perigenual anterior cingulate cortex (pgACC) at 24 h. Understanding the interrelation and time point specificity of ketamine-induced changes of brain circuitry and metabolism is thus key to future therapeutic developments. We investigated the correlation of late glutamatergic changes with FC changes seeded from the posterior cingulate cortex (PCC) and tested the prediction of the latter by acute fractional amplitude of low-frequency fluctuations (fALFF). In a double-blind, randomized, placebo-controlled study of 61 healthy subjects, we compared effects of subanesthetic ketamine infusion (0.5 mg/kg over 40 min) on resting-state fMRI and MR-Spectroscopy at 7 T 1 h and 24 h post-infusion. FC decrease between PCC and dorsomedial prefrontal cortex (dmPFC) was found at 24 h post-infusion (but not 1 h) and this FC decrease correlated with glutamatergic changes at 24 h in pgACC. Acute increase in fALFF was found in ventral PCC at 1 h which was not observed at 24 h and inversely correlated with the reduced dPCC FC towards the dmPFC at 24 h. The correlation of metabolic and functional markers of delayed ketamine effects and their temporal specificity suggest a potential mechanistic relationship between glutamatergic modulation and reconfiguration of brain regions belonging to the DMN.

Anxiety disorders are common and debilitating conditions with higher prevalence in women. However, factors that predispose women to anxiety phenotypes are not clarified. Here we investigated potential contribution of the single nucleotide polymorphism rs2236418 inGAD2gene to changes in regional inhibition/excitation balance, anxiety-like traits, and related neural activity in both sexes. One hundred and five healthy individuals were examined with high-field (7T) multimodal magnetic resonance imaging (MRI); including resting-state functional MRI in combination with assessment of GABA and glutamate (Glu) levels via MR spectroscopy. Regional GABA/Glu levels in anterior cingulate cortex (ACC) subregions were assessed as mediators of gene–personality interaction for the trait harm avoidance and moderation by sex was tested. In AA homozygotes, with putatively lowerGAD2promoter activity, we observed increased intrinsic neuronal activity and higher inhibition/excitation balance in pregenual ACC (pgACC) compared with G carriers. The pgACC drove a significant interaction of genotype, region, and sex, where inhibition/excitation balance was significantly reduced only in female AA carriers. This finding was specific for rs2236418 as other investigated single nucleotide polymorphisms of the GABA synthesis related enzymes (GAD1,GAD2, andGLS) were not significant. Furthermore, only in women there was a negative association of pgACC GABA/Glu ratios with harm avoidance. A moderated-mediation model revealed that pgACC GABA/Glu also mediated the association between the genotype variant and level of harm avoidance, dependent on sex. Our data thus provide new insights into the neurochemical mechanisms that control emotional endophenotypes in humans and constitute predisposing factors for the development of anxiety disorders in women.SIGNIFICANCE STATEMENTAnxiety disorders are among the most common and burdensome psychiatric disorders, with higher prevalence rates in women. The causal mechanisms are, however, poorly understood. In this study we propose a neurobiological basis that could help to explain female bias of anxiety endophenotypes. Using magnetic resonance brain imaging and personality questionnaires we show an interaction of the genetic variation rs2236418 in theGAD2gene and sex on GABA/glutamate (Glu) balance in the pregenual anterior cingulate cortex (pgACC), a region previously connected to affect regulation and anxiety disorders. TheGAD2gene polymorphism further influenced baseline neuronal activity in the pgACC. Importantly, GABA/Glu was shown to mediate the relationship between the genetic variant and harm avoidance, however, only in women.

Background Deep phenotyping and longitudinal assessment of predementia at-risk states of Alzheimer’s disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decline (SCD) is a pre-mild cognitive impairment (pre-MCI) at-risk state of dementia, which emerges as a highly promising target for AD prevention. Methods The German Center for Neurodegenerative Diseases (DZNE) is conducting the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), which focuses on the characterization of SCD in patients recruited from memory clinics. In addition, individuals with amnestic MCI, mild Alzheimer’s dementia patients, first-degree relatives of patients with Alzheimer’s dementia, and cognitively unimpaired control subjects are studied. The total number of subjects to be enrolled is 1000. Participants receive extensive clinical and neuropsychological assessments, magnetic resonance imaging, positron emission tomography, and biomaterial collection is perfomed. In this publication, we report cognitive and clinical data as well as apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) biomarker results of the first 394 baseline data sets. Results In comparison with the control group, patients with SCD showed slightly poorer performance on cognitive and functional measures (Alzheimer’s Disease Assessment Scale—cognitive part, Clinical Dementia Rating, Functional Activities Questionnaire), with all mean scores in a range which would be considered unimpaired. APOE4 genotype was enriched in the SCD group in comparison to what would be expected in the population and the frequency was significantly higher in comparison to the control group. CSF Aβ42 was lower in the SCD group in comparison to the control group at a statistical trend with age as a covariate. There were no group differences in Tau or pTau concentrations between the SCD and the control groups. The differences in all measures between the MCI group and the AD group were as expected. Conclusions The initial baseline data for DELCODE support the approach of using SCD in patients recruited through memory clinics as an enrichment strategy for late-stage preclinical AD. This is indicated by slightly lower performance in a range of measures in SCD in comparison to the control subjects as well as by enriched APOE4 frequency and lower CSF Aβ42 concentration. Trial registration German Clinical Trials Register DRKS00007966 . Registered 4 May 2015.

Purpose To develop a reconstruction pipeline that intrinsically accounts for both simultaneous multislice echo planar imaging (SMS-EPI) reconstruction and dynamic slice-specific Nyquist ghosting correction in time-series data. Methods After 1D slice-group average phase correction, the separate polarity (i.e., even and odd echoes) SMS-EPI data were unaliased by slice GeneRalized Autocalibrating Partial Parallel Acquisition. Both the slice-unaliased even and odd echoes were jointly reconstructed using a model-based framework, extended for SMS-EPI reconstruction that estimates a 2D self-phase map, corrects dynamic slice-specific phase errors, and combines data from all coils and echoes to obtain the final images. Results The percentage ghost-to-signal ratios (%GSRs) and its temporal variations for MB3Ry 2 with a field of view/4 shift in a human brain obtained by the proposed dynamic 2D and standard 1D phase corrections were 1.37 ± 0.11 and 2.66 ± 0.16, respectively. Even with a large regularization parameter λ applied in the proposed reconstruction, the smoothing effect in fMRI activation maps was comparable to a very small Gaussian kernel size 1 × 1 × 1 mm3 . Conclusion The proposed reconstruction pipeline reduced slice-specific phase errors in SMS-EPI, resulting in reduction of GSR. It is applicable for functional MRI studies because the smoothing effect caused by the regularization parameter selection can be minimal in a blood-oxygen-level-dependent activation map.

High field MRI systems, such as 7 Tesla (T) scanners, can deliver higher signal to noise ratio (SNR) than lower field scanners and thus allow for the acquisition of data with higher spatial resolution, which is often demanded by users in the fields of clinical and neuroscientific imaging. However, high resolution scans may require long acquisition times, which in turn increase the discomfort for the subject and the risk of subject motion. Even with a cooperative and trained subject, involuntary motion due to heartbeat, swallowing, respiration and changes in muscle tone can cause image artifacts that reduce the effective resolution. In addition, scanning with higher resolution leads to increased sensitivity to even very small movements. Prospective motion correction (PMC) at 3T and 7T has proven to increase image quality in case of subject motion. Although the application of prospective motion correction is becoming more popular, previous articles focused on proof of concept studies and technical descriptions, whereas this paper briefly describes the technical aspects of the optical tracking system, marker fixation and cross calibration and focuses on the application of PMC to very high resolution imaging without intentional motion. In this study we acquired in vivo MR images at 7T using prospective motion correction during long acquisitions. As a result, we present images among the highest, if not the highest resolution of in vivo human brain MRI ever acquired.

The purpose of this study was to test, for the first time, whether spectroscopy voxels could be positioned automatically with high accuracy and reproducibility in ultrahigh-field longitudinal magnetic resonance spectroscopy (MRS) studies. MRS voxels were automatically positioned in two cingulate subregions of 12 healthy subjects using a vendor-provided automatic voxel positioning (AutoAlign) technique, and were manually placed in the same regions of 10 healthy subjects by an experienced technician in three 7T MRS scan sessions. Different coils were used for manual (24-channel coil) and automatic (32-channel coil) voxel placement, and the effects of signal-to-noise-ratio differences on the spectra were considered. Over three scan sessions and two regions scanned for each subject, a mean voxel geometric overlap ratio of 0.91 for automatic positioning reflected accurate voxel alignment, while the geometric overlap ratio was only 0.70 for voxels placed manually. Comparable voxel positions among the three scan sessions (p > 0.05) indicated high reproducibility of automatic voxel alignment. In comparison, significant voxel displacement among scan sessions (p

Congenital malformations of the optic chiasm, such as enhanced and reduced crossing of the optic nerve fibers, are evident in albinism and achiasma, respectively. In early visual cortex the resulting additional visual input from the ipsilateral visual hemifield is superimposed onto the normal retinotopic representation of the contralateral visual field, which is likely due to conservative geniculo‐striate projections. Counterintuitively, this organization in early visual cortex does not have profound consequences on visual function. Here we ask, whether higher stages of visual processing provide a correction to the abnormal representation allowing for largely normal perception. To this end we assessed the organization patterns of early and ventral visual cortex in five albinotic, one achiasmic, and five control participants. In albinism and achiasma the mirror‐symmetrical superposition of the ipsilateral and contalateral visual fields was evident not only in early visual cortex, but also in the higher areas of the ventral processing stream. Specifically, in the visual areas VO1/2 and PHC1/2 no differences in the extent, the degree of superposition, and the magnitude of the responses were evident in comparison to the early visual areas. Consequently, the highly atypical organization of the primary visual cortex was propagated downstream to highly specialized processing stages in an undiminished and unchanged manner. This indicates largely unaltered cortico‐cortical connections in both types of misrouting, i.e., enhanced and reduced crossing of the optic nerves. It is concluded that main aspects of visual function are preserved despite sizable representation abnormalities in the ventral visual processing stream. Hum Brain Mapp 35:5093–5105, 2014. © 2014 Wiley Periodicals, Inc.

Hemodynamic simulations are restricted by modeling assumptions and uncertain initial and boundary conditions, whereas Phase-Contrast Magnetic Resonance Imaging (PC-MRI) data is affected by measurement noise and artifacts. To overcome the limitations of both techniques, the current study uses a Localization Ensemble Transform Kalman Filter (LETKF) to fully incorporate noisy, low-resolution Phase-Contrast MRI data into an ensemble of high-resolution numerical simulations. The analysis output provides an improved state estimate of the three-dimensional blood flow field in an intracranial aneurysm model. Benchmark measurements are carried out in a silicone phantom model of an idealized aneurysm under pulsatile inflow conditions. Validation is ensured with high-resolution Particle Imaging Velocimetry (PIV) obtained in the symmetry plane of the same geometry. Two data assimilation approaches are introduced, which differ in their way to propagate the ensemble members in time. In both cases the velocity noise is significantly reduced over the whole cardiac cycle. Quantitative and qualitative results indicate an improvement of the flow field prediction in comparison to the raw measurement data. Although biased measurement data reveal a systematic deviation from the truth, the LETKF is able to account for stochastically distributed errors. Through the implementation of the data assimilation step, physical constraints are introduced into the raw measurement data. The resulting, realistic high-resolution flow field can be readily used to assess further patient-specific parameters in addition to the velocity distribution, such as wall shear stress or pressure.

Purpose In this study the potential of diphenhydramine in reducing respectively preventing vertigo and nausea induced by the ultra-high static magnetic field at 7 T was evaluated. Materials and methods In a prospective, double blinded, placebo controlled, cross-over randomized study the sensations of 34 volunteers before, during and after exposure to the static magnetic field with and without drug respectively placebo administration were quantified. Fast table motion was applied to increase the incidence of otherwise sparse reports of field related sensations. Results The strength of vertigo can be reduced by the application of diphenhydramine. Conclusion Diphenhydramine, even at a low dose, reduces the strength of vertigo at ultra-high static magnetic fields, may be used preventively, and could pave the way to even higher field strength.

The neural substrates of feature binding are an old, yet still not completely resolved problem. While patient studies suggest that posterior parietal cortex is necessary for feature binding, imaging evidence has been inconclusive in the past. These studies compared visual feature and conjunction search to investigate the neural substrate of feature conjunctions. However, a common problem of these comparisons was a confound with search difficulty. To circumvent this confound, we directly investigated the localized representation of features (color and spatial frequency) and feature conjunctions in a single search task by using multivariate pattern analysis at high field strength (7T). In right superior parietal lobule, we found evidence for the representation of feature conjunctions that could not be explained by the summation of individual feature representations and thus indicates conjoined processing of color and spatial frequency.

To assess the individual exposure to the static magnetic field (SMF) and the motion-induced time-varying magnetic field (TVMF) generated by activities in an inhomogeneous SMF near high and ultra-high field magnetic resonance imaging (MRI) scanners. The study provides information on the level of exposure to high and ultra-high field MRI scanners during research activities. A three-axis Hall magnetometer was used to determine the SMF and TVMF around human 3- and 7-Tesla (T) MRI systems. The 7-T MRI scanner used in this study was passively shielded and the 3-T scanner was actively shielded and both were from the same manufacturer. The results were compared with the exposure restrictions given by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The recorded exposure was highly variable between individuals, although they followed the same instructions for moving near the scanners. Maximum exposure values of B = 2057 mT and dB/dt = 4347 mT/s for the 3-T scanner and B = 2890 mT, dB/dt = 3900 mT/s for 7 T were recorded. No correlation was found between reporting the MRI-related sensory effects and exceeding the reference values. According to the results of our single-center study with five subjects, violation of the ICNIRP restrictions for max B in MRI research environments was quite unlikely at 3 and 7 T. Occasions of exceeding the dB/dt limit at 3 and 7 T were almost similar (30% of 60 exposure scenarios) and highly variable among the individuals.