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Moeller, S.

Publications and source records attributed to Moeller, S..

At least 19 recordsLinked to original sources

An 80-channel receive array for 10.5T neuroimaging: Key considerations for SNR optimization

PurposeHigh-density RF receive arrays are required to realize the inherently available SNR and parallel imaging advantages at ultrahigh field strengths, which are essential for high-resolution functional and anatomical brain MRI. This study aims to systematically assess the impacts of often-overlooked parasitic losses associated with various RF coil components, as these losses can degrade the realized SNR and cause significant deviation from the ultimate intrinsic SNR (uiSNR; the theoretical upper bound of available SNR). In addition, we seek to detail engineering solutions to each of these loss mechanisms in pursuit of achieving a higher fraction of the uiSNR limit. MethodsA 16-channel loop-folded dipole transceiver array was developed for 10.5T human head applications and paired with a fully-updated 64-channel receive-only loop array. The optimization of the receive array considered several factors, including (but not limited to) coil dimensions to accommodate a larger population, the size and number of loops to enhance SNR and parallel imaging performance, and circuit design strategies to minimize parasitic losses. The SNR and parallel imaging performance of the receive array were quantitatively assessed by comparison with the uiSNR, as well as existing high-channel-count receive arrays at 7T and 10.5T. Finally, the complete 16-channel transmit, 80-channel receive coil array was safety validated for human use and employed for high-resolution functional and anatomical MRI at 10.5T. ResultsInitial results show that the 80-channel array, featuring larger loops in an overlapped layout with optimized circuitry, significantly improves the SNR and approaches the uiSNR limit in a large fraction of the head, while maintaining or enhancing the parallel imaging performance compared to previously used non-overlap layout. ConclusionThis study suggests that, although the traditionally used high-channel-count loop receive array technology can approach the uiSNR limit in the >10T regime, meticulous design optimization--including systematic assessment and minimization of parasitic losses--has become increasingly critical for achieving this goal in this new field-strength territory.

neuroscience↗

Functional MRI of the Human Hippocampus at 10.5T: Pushing the Boundaries of Spatial Resolution

Although the hippocampus is central to human cognition, its deep location within the medial temporal lobe has historically limited fMRI signal quality. Here, we leverage an ultrahigh-field 10.5T fMRI system, which provides inherently higher signal-to-noise ratio than commonly used lower-field systems, to overcome these limitations and achieve unprecedented 0.5 mm isotropic resolution. This advancement allows for comprehensive hippocampal coverage with robust image quality, facilitating the study of functional microcircuits in individual subjects and paving the way for high-precision clinical diagnostics.

neuroscience↗

Bridging the gap with invasive imaging: promises and challenges of a new generation of ultrahigh resolution fMRI

The human neocortex is organized into six laminae forming the structural basis for feedforward and feedback connections across the brain, yet their functional contributions have remained largely inaccessible for non-invasive imaging methods. Leveraging the ultrahigh field of a 10.5 Tesla scanner, we acquired anatomical and functional MRI data at 0.37mm ([~]0.05 {micro}L) and 0.35mm ([~]0.04 {micro}L) isotropic resolution, respectively, approaching the scale of individual cortical layers in humans. Using the Stria of Gennari as an in-vivo anatomical landmark, we extend our previous finding that feedforward visual activation in layer IV of the primary visual cortex during visual stimulation was resolved in laminar BOLD profiles. These laminar features were reproducible across sessions and were not clearly visible with more typical 0.8 mm resolutions at 7T, underscoring the benefits of further increases in magnetic field strength and resolution. This imaging domain, however, comes with increasing challenges of distortion, alignment, and cortical depth estimation, which must be addressed and mitigated to realize its benefits. In this paper we discuss the promises and challenges of this new regime of high resolutions. Our findings showcase the potential of ultrahigh field, ultrahigh resolution human fMRI to bridge the gap with invasive imaging of cortical layers.

neuroscience↗

10.5 Tesla High-Resolution Macaque Brain MRI for Connectivity Studies

Mapping brain connectivity in primates remains a major challenge due to difficulties in resolving microscopic white matter architecture, while maintaining whole-brain coverage. Increasing imaging spatial resolution is key for disambiguating fibre configurations within smaller anatomical volumes. Here, we present novel developments that allow high-resolution diffusion MRI of the macaque brain using one of the world's highest-field human MRI scanners operating at 10.5 Tesla, allowing both in vivo and ex vivo macaque brain imaging. Our approach achieves very high spatial resolution across both tissue states, (up to 580 m)3 in vivo and (300 m)3 ex vivo, with diffusion weighting up to b = 6000 s/mm2. We detail methodological advances in data acquisition, image reconstruction, processing and whole-brain tractography that overcome critical challenges associated with ultra-high-field imaging. This work establishes a new framework for high-resolution in vivo and ex vivo neuroimaging of the NHP brain at 10.5 T using a human bore scanner, paving the way for subsequent analyses of brain connectivity across species and tissue states at unprecedented detail. The dataset, along with all processing pipelines, containerised workflows, and reusable web services, is openly shared to support reproducibility and future integration with microscopy for studying white matter microstructure and connections at the mesoscale.

neuroscience↗

Diffusion-weighted steady-state free precession imaging in the ex vivo macaque brain on a 10.5T human MRI scanner

Diffusion MRI provides a non-invasive probe of local fibre bundles and long-range anatomical connections to characterise the structural connectome. One way to achieve very high spatial resolution diffusion MRI data for connectivity investigations is to scan ex-vivo brains over many hours or days, ideally at ultra-high field strength to boost signal levels. However, conventional diffusion MRI acquisition techniques do not generally deliver good data quality for the challenging conditions of ex-vivo tissue, characterised by reduced diffusivities and relaxation times when compared to in vivo. In this work, we investigate the potential of the diffusion-weighted steady-state free precession (DW-SSFP) sequence for ex vivo diffusion imaging of the macaque brain using a 10.5 T human MRI scanner with a conventional (Gmax = 70 mT/m) gradient set. SNR-efficiency optimisations incorporating experimental relaxation times demonstrate that the DW-SSFP sequence is predicted to achieve improved or similar SNR efficiency compared to a diffusion-weighted spin- and stimulated-echo sequence. Importantly, DW-SSFP can achieve this with the additional benefit of negligible geometric distortions, unlike conventional diffusion MRI using an echo-planar imaging readout. Using optimised DW-SSFP sequence parameters, we propose a protocol at 0.4 mm isotropic resolution using a two-shell multi-orientation protocol (effective b-values of 3200 s/mm2 and 5600 s/mm2). We fit the data using Tensor, Ball and 3-Sticks and Constrained Spherical Deconvolution signal representations. The results demonstrate high-quality diffusivity estimates across the entire brain with the ability to resolve multiple fibre populations in challenging crossing-fibre regions. The data will be made fully open source and multimodal as part of the Center for Mesoscale Connectomics, providing a resource for future connectivity investigations.

neuroscience↗

An RF coil array system for in vivo & ex vivo non-human primate brain studies at 10.5 Tesla

PurposeWe aimed to develop an innovative RF coil toolset for high resolution in vivo and ex vivo non-human primate neuroimaging applications at 10.5T MRI. The main goal was to improve our multimodal neural connectivity pipeline through the improved SNR, CNR, and spatial resolution that result from utilizing high-density RF coil arrays in combination with ultra-high field MRI. MethodsTwo RF coil arrays, both comprising 8 transmit and 40 receive channels, were designed and built for in vivo and ex vivo NHP imaging at 10.5 T. Experimental data was collected on multiple in vivo and ex vivo specimens, showing the utility UHF MRI for NHP neuroscience. ResultsExperimental results demonstrate uniform whole-brain coverage within both in vivo--which included the cerebellar, and spinal cord regions--and ex vivo specimens. High spatial resolutions (in vivo: 0.1x0.1x0.5 mm, ex vivo: 120 micron isotropic) were achieved, revealing detailed anatomical structures throughout. High temporal stability allowed for EPI and dMRI applications. ConclusionAn RF coil toolset comprising two 8ch transmit/40ch receive arrays was successfully designed for both in vivo and ex vivo NHP brain applications at 10.5 T. Both high-density RF coil arrays coupled with the SNR and CNR benefits available at UHF supported unmatched anatomical, functional, and diffusion applications at some of the highest spatial resolutions to date. Additionally, the combined capability of both in vivo and ex vivo MRI with the same brain specimen allows for tighter control for experimental-paradigm multistage studies examining translation between in vivo and ex vivo methodologies.

neuroscience↗

Spanning spatial scales with functional imaging in the human brain; initial experiences at 10.5 Tesla

One of the most important frontiers in the efforts to improve functional imaging of brain activity (fMRI) is the recent push to increase the magnetic fields for human imaging beyond 10 Tesla. Having established safety, large gains in signal-to-noise-ratio (SNR), and novel radiofrequency arrays that capture the higher SNR, here we demonstrate major gains in the spatial resolution, sensitivity, and functional contrast of BOLD (Blood Oxygenation Level Dependent) based human fMRI at 10.5 Tesla. Using image reconstruction methods developed to minimize blurring, we also demonstrate that ultrahigh resolutions achieved at 10.5 Tesla suppress large-vein confounds in gradient-recalled-echo BOLD fMRI, thus improving the fidelity of functional signals relative to neuronal activity and yielding accurate cortical depth-profiles for layer-specific activation. Together, these multiplicative benefits deliver much needed increases in precision and resolution for meso-scale fMRI applications and illustrate the transformative potential of human functional imaging at magnetic fields that exceed 10 Tesla.

neuroscience↗

A 128-channel receive array with enhanced SNR performance for 10.5 tesla brain imaging

PurposeTo develop and characterize the performance of a 128-channel head array for brain imaging at 10.5 tesla and evaluate the potential of brain imaging at this unique, >10 tesla magnetic field. MethodsThe coil is composed of a 16-channel self-decoupled loop transmit/receive array with a 112-loop receive-only (Rx) insert. Interactions between the outer transmitter and the inner 112Rx insert were mitigated using coaxial cable traps placed every 1/16 of a wavelength on each feed cable, locating most preamplifier boards outside the transmitter field and miniaturizing those placed directly on individual coils. ResultsThe 128-channel array described herein achieved 77% of ultimate intrinsic SNR in the center of the brain. Transmit field maps obtained experimentally on a phantom with and without the receive array were similar and matched EM simulations, leading to FDA approval for human imaging. Anatomical and functional data, including with power demanding sequences, were acquired successfully on human volunteers. ConclusionsCounterintuitive to expectations based on magnetic fields [≤]7T, the higher channel counts provided SNR gains centrally, capturing [~]80% uiSNR. Fraction of uiSNR achieved centrally in 64Rx, 80Rx, and 128Rx arrays suggested that a plateau was being reached at 80%. At this plateau, linear to approximately quadratic B0 dependent SNR gains for the periphery and the center, respectively, were observed for 10.5T relative 7T.

neuroscience↗

RF coil design strategies for improving SNR at theultrahigh magnetic field of 10.5 Tesla

PurposeTo develop multichannel transmit and receive arrays towards capturing the ultimate-intrinsic-SNR (uiSNR) at 10.5 Tesla (T) and to demonstrate the feasibility and potential of whole-brain, high-resolution human brain imaging at this high field strength. MethodsA dual row 16-channel self-decoupled transmit (Tx) array was converted to a 16Tx/Rx transceiver using custom transmit/receive switches. A 64-channel receive-only (64Rx) array was built to fit into the 16Tx/Rx array. Electromagnetic modeling and experiments were employed to define safe operation limits of the resulting 16Tx/80Rx array and obtain FDA approval for human use. ResultsThe 64Rx array alone captured approximately 50% of the central uiSNR at 10.5T while the identical 7T 64Rx array captured [~]76% of uiSNR at this lower field strength. The 16Tx/80Rx configuration brought the fraction of uiSNR captured at 10.5T to levels comparable to the performance of the 64Rx array at 7T. SNR data obtained at the two field strengths with these arrays displayed [Formula] dependent increases over a large central region. Whole-brain high resolution T2* and T1 weighted anatomical and gradient-recalled echo EPI BOLD fMRI images were obtained at 10.5T for the first time with such an advanced array, illustrating the promise of >10T fields in studying the human brain. ConclusionWe demonstrated the ability to approach the uiSNR at 10.5T over the human brain with a novel, high channel count array, achieving large SNR gains over 7T, currently the most commonly employed ultrahigh field platform, and demonstrate high resolution and high contrast anatomical and functional imaging at 10.5T.

neuroscience↗

Mapping polarization-sensitive optical coherence tomography and ultra-high-field diffusion MRI in the macaque brain

This paper provides comparisons between microstructure and two-dimensional fiber orientations measured optically using polarization sensitive optical coherence tomography (PS-OCT) and those estimated from ultra-high-field diffusion MRI (dMRI) at 10.5T in the macaque brain. The PS-OCT imaging is done at an in-plane resolution of [~]10 microns in and around the thalamus. Whole brain dMRI is acquired at an isotropic resolution of 0.75 mm. We provide comparisons between cross-polarization and optical orientation from PS-OCT with the fractional anisotropy and two-dimensional orientations extracted from dMRI using a diffusion tensor model. The orientations from PS-OCT are also extracted computationally using a structure tensor. Additionally, we demonstrate the utility of mesoscale, PS-OCT imaging in improving the MRI resolution by learning the mapping between these contrasts using a super-resolution Generative Adversarial Network.

neuroscience↗

Evaluating the effect of denoising submillimeter auditory fMRI data with NORDIC

Functional magnetic resonance imaging (fMRI) has emerged as an essential tool for exploring human brain function. Submillimeter fMRI, in particular, has emerged as a tool to study mesoscopic computations. The inherently low signal-to-noise ratio (SNR) at submillimeter resolutions warrants the use of denoising approaches tailored at reducing thermal noise - the dominant contributing noise component in high resolution fMRI. NORDIC PCA is one of such approaches, and has been benchmarked against other approaches in several applications. Here, we investigate the effects that two versions of NORDIC denoising have on auditory submillimeter data. As investigating auditory functional responses poses unique challenges, we anticipated that the benefit of this technique would be especially pronounced. Our results show that NORDIC denoising improves the detection sensitivity and the reliability of estimates in submillimeter auditory fMRI data. These effects can be explained by the reduction of the noise-induced signal variability. However, we also observed a reduction in the average response amplitude (percent signal), which may suggest that a small amount of signal was also removed. We conclude that, while evaluating the effects of the signal reduction induced by NORDIC may be necessary for each application, using NORDIC in high resolution auditory fMRI studies may be advantageous because of the large reduction in variability of the estimated responses.

neuroscience↗

Locally low-rank denoising in transform domains

PurposeTo develop an extension to locally low rank (LLR) denoising techniques based on transform domain processing that reduces the number of images required in the MR image series for high-quality denoising. Theory and MethodsLLR methods with random matrix theory-based thresholds are successfully used in the denoising of MR image series in a number of applications. The performance of these methods depend on how well the LLR assumption is satisfied, which deteriorates with few numbers of images, as is commonly encountered in quantitative MRI applications. We propose a transform-domain approach for denoising of MR image series to represent the underlying signal with higher fidelity when using a locally low rank approximation. The efficacy of the method is demonstrated for fully-sampled k-space, undersampled k-space, DICOM images, and complex-valued SENSE-1 images in quantitative MRI applications with as few as 4 images. ResultsFor both MSK and brain applications, the transform domain denoising preserves local subtle variability, whereas the quantitative maps based on image domain LLR methods tend to be locally more homogeneous. ConclusionA transform domain extension to LLR denoising produces high quality images and is compatible with both raw k-space data and vendor reconstructed data. This allows for improved imaging and more accurate quantitative analyses and parameters obtained therefrom.

scientific communication and education↗

Denoising Diffusion MRI: Considerations and implications for analysis

Development of diffusion MRI (dMRI) denoising approaches has experienced considerable growth over the last years. As noise can inherently reduce accuracy and precision in measurements, its effects have been well characterised both in terms of uncertainty increase in dMRI-derived features and in terms of biases caused by the noise floor, the smallest measurable signal given the noise level. However, gaps in our knowledge still exist in objectively characterising dMRI denoising approaches in terms of both of these effects and assessing their efficacy. In this work, we reconsider what a denoising method should and should not do and we accordingly define criteria to characterise the performance. We propose a comprehensive set of evaluations, including i) benefits in improving signal quality and reducing noise variance, ii) gains in reducing biases and the noise floor and improving, iii) preservation of spatial resolution, iv) agreement of denoised data against a gold standard, v) gains in downstream parameter estimation (precision and accuracy), vi) efficacy in enabling noise-prone applications, such as ultra-high-resolution imaging. We further provide newly acquired complex datasets (magnitude and phase) with multiple repeats that sample different SNR regimes to highlight performance differences under different scenarios. Without loss of generality, we subsequently apply a number of exemplar patch-based denoising algorithms to these datasets, including Non-Local Means, Marchenko-Pastur PCA (MPPCA) in the magnitude and complex domain and NORDIC, and compare them with respect to the above criteria and against a gold standard complex average of multiple repeats. We demonstrate that all tested denoising approaches reduce noise-related variance, but not always biases from the elevated noise floor. They all induce a spatial resolution penalty, but its extent can vary depending on the method and the implementation. Some denoising approaches agree with the gold standard more than others and we demonstrate challenges in even defining such a standard. Overall, we show that dMRI denoising performed in the complex domain is advantageous to magnitude domain denoising with respect to all the above criteria.

neuroscience↗

Activating the NFE2L1-ubiquitin-proteasome system by DDI2 protects from ferroptosis

Ferroptosis is an iron-dependent, non-apoptotic form of cell death initiated by oxidative stress and lipid peroxidation. Recent evidence has linked ferroptosis to the action of the transcription factor Nuclear factor erythroid-2 derived,-like-1 (NFE2L1). NFE2L1 regulates proteasome abundance in an adaptive fashion, maintaining protein quality control to secure cellular homeostasis, but the regulation of NFE2L1 during ferroptosis and the role of the ubiquitin-proteasome system (UPS) herein are still unclear. In the present study, using an unbiased proteomic approach charting the specific ubiquitylation sites, we show that induction of ferroptosis leads to recalibration of the UPS. RSL3-induced ferroptosis inhibits proteasome activity and leads to global hyperubiquitylation, which is linked to NFE2L1 activation. As NFE2L1 resides in the endoplasmic reticulum tethered to the membrane, it undergoes complex posttranslational modification steps to become active and induce the expression of proteasome subunit genes. We show that proteolytic cleavage of NFE2L1 by the aspartyl protease DNA-damage inducible 1 homolog 2 (DDI2) is a critical step for the ferroptosis-induced feed-back loop of proteasome function. Cells lacking DDI2 cannot activate NFE2L1 in response to RSL3 and show global hyperubiquitylation. Genetic or chemical induction of ferroptosis in cells with a disrupted DDI2-NFE2L1 pathway diminishes proteasomal activity and promotes cell death. Also, treating cells with the clinical drug nelfinavir, which inhibits DDI2, sensitized cells to ferroptosis. In conclusion, our results provide new insight into the importance of the UPS in ferroptosis and highlight the role of the DDI2-NFE2L1 as a potential therapeutic target. Manipulating DDI2-NFE2L1 activity through chemical inhibition might help sensitizing cells to ferroptosis, thus enhancing existing cancer therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/547652v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@b3f899org.highwire.dtl.DTLVardef@18625feorg.highwire.dtl.DTLVardef@287bcborg.highwire.dtl.DTLVardef@1d758d1_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Task Demands Differentiate Regional Depth-Dependent Activity Profiles Within the Ventral Visual Pathway

FMRI has become a key tool for human neuroscience. At ultra-high field (=> 7 Tesla) it is possible to acquire images with submillimeter spatial precision, which allows examinations of mesoscale functional organization. Studying the brain at this scale does not come without its challenges, however. To tackle some of these challenges, we propose an approach that builds upon task modulations to identical visual stimuli and the simultaneous imaging of distal areas of varying complexity across the cortical hierarchy. Specifically, we record BOLD responses elicited by face stimuli during a stimulus relevant and a stimulus irrelevant task across cortical depths in V1, Occipital Face (OFA) and Fusiform Face area (FFA). We observed that task-related top-down modulations were larger in the inner compared to the outer layers of V1; and in the outer compared to the inner layers in the FFA. Our findings are consistent with animal reports of feedback exchange between deeper and superficial layers and with the notion of apical dendritic amplification as a key mechanism of conscious perception. Our approach showcases the potential of "laminar-fMRI" to explore large scale network activity and represents a promising step towards characterizing laminar functional profiles in humans for complex, cognitively meaningful, and socially relevant stimuli such as faces.

neuroscience↗

Ubigen: Interactive Ranking and Enrichment Test for Ubiquitously Expressed Genes

We provide an interactive web service to score and rank human genes by their abundance and invariance of expression across all samples in the GTEx database. Users may provide a list of genes to have these scored and ranked accordingly. A one-sided Wilcoxon rank sum test determines a p-value to indicate if the genes from the list score higher than expected by chance. It is possible to interactively control the parameters and instantly observe the effects on the ranking for each of the submitted genes of interest. A genome-wide sliding-window analysis finds that the genes with both the highest and the lowest ranks feature more GO term annotations, indicating that the scoring carries biological relevance. Availability and Implementationhttps://ubigen.uni-rostock.de Contactelias.projahn@uni-rostock.de

bioinformatics↗

Improving Sensitivity to Functional Responses without a Loss of Spatiotemporal Precision in Human Brain Imaging

As the neuroimaging field moves towards detecting smaller effects at higher spatial resolutions, and faster sampling rates, there is increased attention given to the deleterious contribution of unstructured, thermal noise. Here, we critically evaluate the performance of a recently developed reconstruction method, termed NORDIC, for suppressing thermal noise using datasets acquired with various field strengths, voxel sizes, sampling rates, and task designs. Following minimal preprocessing, statistical activation (t-values) of NORDIC processed data was compared to the results obtained with alternative denoising methods. Additionally, we examined the consistency of the estimates of task responses at the single-voxel, single run level, using a finite impulse response (FIR) model. To examine the potential impact on effective image resolution, the overall smoothness of the data processed with different methods was estimated. Finally, to determine if NORDIC alters or removes important temporal information, we employed an exhaustive leave-p-out cross validation approach, using FIR task responses to predict held out timeseries, quantified using R2. After NORDIC, the t-values are increased, an improvement comparable to what could be achieved by 1.5 voxels smoothing, and task events are clearly visible and have less cross-run error. These advantages are achieved in the absence of large changes in estimates of spatial smoothness. Cross-validated R2s based on the FIR models show that NORDIC is not measurably distorting the temporal structure of the data and is the best predictor of non-denoised time courses. The results demonstrate that analyzing 1 run of data after NORDIC produces results equivalent to using 2 to 3 original runs and that NORDIC performs equally well across a diverse array of functional imaging protocols. Significance StatementFor functional neuroimaging, the increasing availability of higher field strengths and ever higher spatiotemporal resolutions has led to concomitant increase in concerns about the deleterious effects of thermal noise. Historically this noise source was suppressed using methods that reduce spatial precision such as image blurring or averaging over a large number of trials or sessions, which necessitates large data collection efforts. Here, we critically evaluate the performance of a recently developed reconstruction method, termed NORDIC. Across datasets varying in field strength, voxel sizes, sampling rates, and task designs, NORDIC produces substantial gains in data quality. Both conventional t-statistics derived from general linear models and coefficients of determination for predicting unseen data are improved, while avoiding meaningful increases in typical estimates of image smoothness or substantial losses of temporal information.

neuroscience↗

A Paradigm Change in Functional Brain Mapping: Suppressing the Thermal Noise in fMRI

Functional magnetic resonance imaging (fMRI) has become one of the most powerful tools for investigating the human brain. However, virtually all fMRI studies have relatively poor signal-to-noise ratio (SNR). Here we introduce a novel fMRI denoising technique, which suppresses noise that is indistinguishable from zero-mean, Gaussian-distributed noise. Thermal noise, falling in this category, is a major source of noise in fMRI, particularly, but not exclusively, at high spatial and/or temporal resolutions. Using 7-Tesla high-resolution data, we demonstrate improvements in temporal-SNR, the detection of stimulus-induced signal changes, and functional maps, while leaving stimulus-induced signal change amplitudes, image spatial precision, and functional point-spread-function unaltered. We also show that the method is equally applicable when using supra-millimeter resolution 3- and 7-Tesla fMRI data, different cortical regions, stimulation/task paradigms, and acquisition strategies. This denoising approach improves key metrics of functional activation detection while preserving spatial precision.

neuroscience↗