Insights into hippocampal perfusion using high-resolution, multi-modal 7T MRI.

We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated robust perfusion maps and observed significant variations in perfusion among hippocampal subfields, with CA1 exhibiting the lowest perfusion levels. Notably, these perfusion differences were robust and already detectable with 50 perfusion-weighted images per subject, acquired in 5 min. To understand the underlying factors, we examined the influence of image quality metrics, various tissue microstructure and morphometric properties, macrovasculature, and cytoarchitecture. We observed higher perfusion in regions located closer to arteries, demonstrating the influence of vascular proximity on hippocampal perfusion. Moreover, ex vivo cytoarchitectonic features based on neuronal density differences appeared to correlate stronger with hippocampal perfusion than morphometric measures like gray matter thickness. These findings emphasize the interplay between microvasculature, macrovasculature, and metabolic demand in shaping hippocampal perfusion. Our study expands the current understanding of hippocampal physiology and its relevance to neurological disorders. By providing in vivo evidence of perfusion differences between hippocampal subfields, our findings have implications for diagnosis and potential therapeutic interventions. In conclusion, our study provides a valuable resource for extensively characterizing hippocampal perfusion.

Microstructural associations between locus coeruleus, cortical, and subcortical regions are modulated by astrocyte reactivity: a 7T MRI adult lifespan study.

The locus coeruleus-norepinephrine system plays a key role in supporting brain health along the lifespan, notably through its modulatory effects on neuroinflammation. Using ultra-high field diffusion magnetic resonance imaging, we examined whether microstructural properties (neurite density index and orientation dispersion index) in the locus coeruleus were related to those in cortical and subcortical regions, and whether this was modulated by plasma glial fibrillary acidic protein levels, as a proxy of astrocyte reactivity. In our cohort of 60 healthy individuals (30 to 85 yr, 50% female), higher glial fibrillary acidic protein correlated with lower neurite density index in frontal cortical regions, the hippocampus, and the amygdala. Furthermore, under higher levels of glial fibrillary acidic protein (above ~ 150 pg/mL for cortical and ~ 145 pg/mL for subcortical regions), lower locus coeruleus orientation dispersion index was associated with lower orientation dispersion index in frontotemporal cortical regions and in subcortical regions. Interestingly, individuals with higher locus coeruleus orientation dispersion index exhibited higher orientation dispersion index in these (sub)cortical regions, despite having higher glial fibrillary acidic protein levels. Together, these results suggest that the interaction between locus coeruleus-norepinephrine cells and astrocytes can signal a detrimental or neuroprotective pathway for brain integrity and support the importance of maintaining locus coeruleus neuronal health in aging and in the prevention of age-related neurodegenerative diseases.

Comparing the efficacy of data-driven denoising methods for a multi-echo fMRI acquisition at 7T.

In functional magnetic resonance imaging (fMRI) of the brain the measured signal is corrupted by several (e.g. physiological, motion, and thermal) noise sources and depends on the image acquisition. Imaging at ultrahigh field strength is becoming increasingly popular as it offers increased spatial accuracy. The latter is of particular benefit in brainstem neuroimaging given the small cross-sectional area of most nuclei. However, physiological noise scales with field strength in fMRI acquisitions. Although this problem is in part solved by decreasing voxel size, it is clear that adequate physiological denoising is of utmost importance in brainstem-focused fMRI experiments. Multi-echo sequences have been reported to facilitate highly effective denoising through TE-dependence of Blood Oxygen Level Dependent (BOLD) signals, in a denoising method referred to as multi-echo independent component analysis (ME-ICA). It has not been explored previously how ME-ICA compares to other data-driven denoising approaches at ultrahigh field strength. In the current study, we compared the efficacy of several denoising methods, including anatomical component based correction (aCompCor), Automatic Removal of Motion Artifacts (ICA-AROMA) aggressive and non-aggressive options, ME-ICA, and a combination of ME-ICA and aCompCor. We assessed several data quality metrics, including temporal signal-to-noise ratio (tSNR), delta variation signal (DVARS), spectral density of the global signal, functional connectivity and Shannon spectral entropy. Moreover, we looked at the ability of each method to uncouple the global signal and respiration. In line with previous reports at lower field strengths, we demonstrate that after applying ME-ICA, the data is best post-processed in order to remove spatially diffuse noise with a method such as aCompCor. Our findings indicate that ME-ICA combined with aCompCor and the aggressive option of ICA-AROMA are highly effective denoising approaches for multi-echo data acquired at 7T. ME-ICA combined with aCompCor potentially preserves more signal-of-interest as compared to the aggressive option of ICA-AROMA.

Combining arterial blood contrast with BOLD increases fMRI intracortical contrast.

BOLD fMRI is widely applied in human neuroscience but is limited in its spatial specificity due to a cortical-depth-dependent venous bias. This reduces its localization specificity with respect to neuronal responses, a disadvantage for neuroscientific research. Here, we modified a submillimeter BOLD protocol to selectively reduce venous and tissue signal and increase cerebral blood volume weighting through a pulsed saturation scheme (dubbed Arterial Blood Contrast) at 7 T. Adding Arterial Blood Contrast on top of the existing BOLD contrast modulated the intracortical contrast. Isolating the Arterial Blood Contrast showed a response free of pial-surface bias. The results suggest that Arterial Blood Contrast can modulate the typical fMRI spatial specificity, with important applications in in-vivo neuroscience.

A comparison of multiband and multiband multiecho gradient-echo EPI for task fMRI at 3 T.

A multiband (MB) echo-planar imaging (EPI) sequence is compared to a multiband multiecho (MBME) EPI protocol to investigate differences in sensitivity for task functional magnetic resonance imaging (fMRI) at 3 T. Multiecho sampling improves sensitivity in areas where single-echo-EPI suffers from dropouts. However, It requires in-plane acceleration to reduce the echo train length, limiting the slice acceleration factor and the temporal and spatial resolution Data were acquired for both protocols in two sessions 24 h apart using an adapted color-word interference Stroop task. Besides protocol comparison statistically, we performed test-retest reliability across sessions for different protocols and denoising methods. We evaluated the sensitivity of two different echo-combination strategies for MBME-EPI. We examined the performance of three different data denoising approaches: "Standard," "AROMA," and "FIX" for MB and MBME, and assessed whether a specific method is preferable. We consider using an appropriate autoregressive model order within the general linear model framework to correct TR differences between the protocols. The comparison between protocols and denoising methods showed at group level significantly higher mean z-scores and the number of active voxels for MBME in the motor, subcortical and medial frontal cortices. When comparing different echo combinations, our results suggest that a contrast-to-noise ratio weighted echo combination improves sensitivity in MBME compared to simple echo-summation. This study indicates that MBME can be a preferred protocol in task fMRI at spatial resolution (≥2 mm), primarily in medial prefrontal and subcortical areas.

3D-EPI blip-up/down acquisition (BUDA) with CAIPI and joint Hankel structured low-rank reconstruction for rapid distortion-free high-resolution T 2 * mapping.

PURPOSE: This work aims to develop a novel distortion-free 3D-EPI acquisition and image reconstruction technique for fast and robust, high-resolution, whole-brain imaging as well as quantitative T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping. METHODS: 3D Blip-up and -down acquisition (3D-BUDA) sequence is designed for both single- and multi-echo 3D gradient recalled echo (GRE)-EPI imaging using multiple shots with blip-up and -down readouts to encode B0 field map information. Complementary k-space coverage is achieved using controlled aliasing in parallel imaging (CAIPI) sampling across the shots. For image reconstruction, an iterative hard-thresholding algorithm is employed to minimize the cost function that combines field map information informed parallel imaging with the structured low-rank constraint for multi-shot 3D-BUDA data. Extending 3D-BUDA to multi-echo imaging permits T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping. For this, we propose constructing a joint Hankel matrix along both echo and shot dimensions to improve the reconstruction. RESULTS: Experimental results on in vivo multi-echo data demonstrate that, by performing joint reconstruction along with both echo and shot dimensions, reconstruction accuracy is improved compared to standard 3D-BUDA reconstruction. CAIPI sampling is further shown to enhance image quality. For T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping, parameter values from 3D-Joint-CAIPI-BUDA and reference multi-echo GRE are within limits of agreement as quantified by Bland-Altman analysis. CONCLUSIONS: The proposed technique enables rapid 3D distortion-free high-resolution imaging and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping. Specifically, 3D-BUDA enables 1-mm isotropic whole-brain imaging in 22 s at 3T and 9 s on a 7T scanner. The combination of multi-echo 3D-BUDA with CAIPI acquisition and joint reconstruction enables distortion-free whole-brain T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping in 47 s at 1.1 × 1.1 × 1.0 mm3 resolution.

Magnetic resonance imaging at 9.4 T: the Maastricht journey.

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Concurrent CBF and BOLD FMRI with dual-echo spiral simultaneous multi-slice acquisitions at 7T.

Measurement of cerebral blood flow (CBF) using the Arterial Spin Labeling (ASL) technique is a desirable fMRI approach due to the higher specificity of CBF to the site of neural activation. However, ASL has inherent limitations, such as a low signal-to-noise ratio (SNR) and low coverage/resolution due to the limited readout window following the labeling. Recently, ASL has been implemented at ultra-high field (UHF) strengths in an attempt to mitigate the SNR challenges. Even though ASL intrinsically allows concurrent acquisition of CBF and BOLD contrasts, a compromise in the echo time (TE) for either of the contrasts is inevitable with single-echo acquisitions. Long durations of the Cartesian EPI readout do not allow for multi-echo acquisitions for resolutions ≤2 mm where both contrasts can be acquired at their optimal TE at UHF. With its higher acquisition efficiency, single-shot spiral imaging provides a promising alternative to EPI, and with a dual-echo, out-in trajectory allows both CBF and BOLD contrasts to be acquired at their respective optimal TE. In this work, we implemented a dual-echo spiral out-in ASL sequence with simultaneous multi-slice (SMS) readout for increased coverage, and validated its application to fMRI with a visuomotor paradigm. Conventional Cartesian EPI acquisitions with matched parameters served as a reference. The dual-echo spiral ASL acquisitions resulted in robust CBF and BOLD activations maps. The absolute and relative CBF changes measured with the dual-echo spiral readout were in agreement with previous reports in the literature as well as the reference Cartesian acquisitions. The BOLD response amplitude was higher compared to the Cartesian acquisitions, attributable to a more optimal TE of the second echo. In conclusion, dual-echo spiral out-in SMS acquisition shows promise for concurrent acquisitions of BOLD and non-BOLD contrasts that require a short TE, with no loss in temporal resolution.

Asymmetric representation of aversive prediction errors in Pavlovian threat conditioning.

Survival in biological environments requires learning associations between predictive sensory cues and threatening outcomes. Such aversive learning may be implemented through reinforcement learning algorithms that are driven by the signed difference between expected and encountered outcomes, termed prediction errors (PEs). While PE-based learning is well established for reward learning, the role of putative PE signals in aversive learning is less clear. Here, we used functional magnetic resonance imaging in humans (21 healthy men and women) to investigate the neural representation of PEs during maintenance of learned aversive associations. Four visual cues, each with a different probability (0, 33, 66, 100%) of being followed by an aversive outcome (electric shock), were repeatedly presented to participants. We found that neural activity at omission (US-) but not occurrence of the aversive outcome (US+) encoded PEs in the medial prefrontal cortex. More expected omission of aversive outcome was associated with lower neural activity. No neural signals fulfilled axiomatic criteria, which specify necessary and sufficient components of PE signals, for signed PE representation in a whole-brain search or in a-priori regions of interest. Our results might suggest that, different from reward learning, aversive learning does not involve signed PE signals that are represented within the same brain region for all conditions.

Mesoscopic in vivo human T2* dataset acquired using quantitative MRI at 7 Tesla.

Mesoscopic (0.1-0.5 mm) interrogation of the living human brain is critical for advancing neuroscience and bridging the resolution gap with animal models. Despite the variety of MRI contrasts measured in recent years at the mesoscopic scale, in vivo quantitative imaging of T2* has not been performed. Here we provide a dataset containing empirical T2* measurements acquired at 0.35 × 0.35 × 0.35 mm3 voxel resolution using 7 Tesla MRI. To demonstrate unique features and high quality of this dataset, we generate flat map visualizations that reveal fine-scale cortical substructures such as layers and vessels, and we report quantitative depth-dependent T2* (as well as R2*) values in primary visual cortex and auditory cortex that are highly consistent across subjects. This dataset is freely available at https://doi.org/10.17605/OSF.IO/N5BJ7, and may prove useful for anatomical investigations of the human brain, as well as for improving our understanding of the basis of the T2*-weighted (f)MRI signal.

BUDA-MESMERISE: Rapid acquisition and unsupervised parameter estimation for T1 , T2 , M0 , B0 , and B1 maps.

PURPOSE: Rapid acquisition scheme and parameter estimation method are proposed to acquire distortion-free spin- and stimulated-echo signals and combine the signals with a physics-driven unsupervised network to estimate T1 , T2 , and proton density (M0 ) parameter maps, along with B0 and B1 information from the acquired signals. THEORY AND METHODS: An imaging sequence with three 90° RF pulses is utilized to acquire spin- and stimulated-echo signals. We utilize blip-up/-down acquisition to eliminate geometric distortion incurred by the effects of B0 inhomogeneity on rapid EPI acquisitions. For multislice imaging, echo-shifting is applied to utilize dead time between the second and third RF pulses to encode information from additional slice positions. To estimate parameter maps from the spin- and stimulated-echo signals with high fidelity, 2 estimation methods, analytic fitting and a novel unsupervised deep neural network method, are developed. RESULTS: The proposed acquisition provided distortion-free T1 , T2 , relative proton density (M0), B0 , and B1 maps with high fidelity both in phantom and in vivo brain experiments. From the rapidly acquired spin- and stimulated-echo signals, analytic fitting and the network-based method were able to estimate T1 , T2 , M0 , B0 , and B1 maps with high accuracy. Network estimates demonstrated noise robustness owing to the fact that the convolutional layers take information into account from spatially adjacent voxels. CONCLUSION: The proposed acquisition/reconstruction technique enabled whole-brain acquisition of coregistered, distortion-free, T1 , T2 , M0 , B0 , and B1 maps at 1 × 1 × 5 mm3 resolution in 50 s. The proposed unsupervised neural network provided noise-robust parameter estimates from this rapid acquisition.

Highly accelerated EPI with wave encoding and multi-shot simultaneous multislice imaging.

PURPOSE: To introduce wave-encoded acquisition and reconstruction techniques for highly accelerated EPI with reduced g-factor penalty and image artifacts. THEORY AND METHODS: Wave-EPI involves application of sinusoidal gradients during the EPI readout, which spreads the aliasing in all spatial directions, thereby taking better advantage of 3D coil sensitivity profiles. The amount of voxel spreading that can be achieved by the wave gradients during the short EPI readout period is constrained by the slew rate of the gradient coils and peripheral nerve stimulation monitor. We propose to use a "half-cycle" sinusoidal gradient to increase the amount of voxel spreading that can be achieved while respecting the slew and stimulation constraints. Extending wave-EPI to multi-shot acquisition minimizes geometric distortion and voxel blurring at high in-plane resolutions, while structured low-rank regularization mitigates shot-to-shot phase variations. To address gradient imperfections, we propose to use different point spread functions for the k-space lines with positive and negative polarities, which are calibrated with a FLEET-based reference scan. RESULTS: Wave-EPI enabled whole-brain single-shot gradient-echo (GE) and multi-shot spin-echo (SE) EPI acquisitions at high acceleration factors at 3T and was combined with g-Slider encoding to boost the SNR level in 1 mm isotropic diffusion imaging. Relative to blipped-CAIPI, wave-EPI reduced average and maximum g-factors by up to 1.21- and 1.37-fold at Rin × Rsms  = 3 × 3, respectively. CONCLUSION: Wave-EPI allows highly accelerated single- and multi-shot EPI with reduced g-factor and artifacts and may facilitate clinical and neuroscientific applications of EPI by improving the spatial and temporal resolution in functional and diffusion imaging.

Magnetic field strength dependent SNR gain at the center of a spherical phantom and up to 11.7T.

PURPOSE: The SNR at the center of a spherical phantom of known electrical properties was measured in quasi-identical experimental conditions as a function of magnetic field strength between 3 T and 11.7 T. METHODS: The SNR was measured at the center of a spherical water saline phantom with a gradient-recalled echo sequence. Measurements were performed at NeuroSpin at 3, 7, and 11.7 T. The phantom was then shipped to Maastricht University and then to the University of Minnesota for additional data points at 7, 9.4, and 10.5 T. Experiments were carried out with the exact same type of birdcage volume coil (except at 3 T, where a similar coil was used) to attempt at isolating the evolution of SNR with field strength alone. Phantom electrical properties were characterized over the corresponding frequency range. RESULTS: Electrical properties were found to barely vary over the frequency range. Removing the influence of the flip-angle excitation inhomogeneity was crucial, as expected. After such correction, measurements revealed a gain of SNR growing as B0 1.94 ± 0.16 compared with B0 2.13 according to ultimate intrinsic SNR theory. CONCLUSIONS: By using quasi-identical experimental setups (RF volume coil, phantom, electrical properties, and protocol), this work reports experimental data between 3 T and 11.7 T, enabling the comparison with SNR theories in which conductivity and permittivity can be assumed to be constant with respect to field strength. According to ultimate SNR theory, these results can be reasonably extrapolated to the performance of receive arrays with greater than about 32 elements for central SNR in the same spherical phantom.

Magnetization transfer weighted EPI facilitates cortical depth determination in native fMRI space.

The increased availability of ultra-high field scanners provides an opportunity to perform fMRI at sub-millimeter spatial scales and enables in vivo probing of laminar function in the human brain. In most previous studies, the definition of cortical layers, or depths, is based on an anatomical reference image that is collected by a different acquisition sequence and exhibits different geometric distortion compared to the functional images. Here, we propose to generate the anatomical image with the fMRI acquisition technique by incorporating magnetization transfer (MT) weighted imaging. Small flip angle binomial pulse trains are used as MT preparation, with a flexible duration (several to tens of milliseconds), which can be applied before each EPI segment without constraining the acquisition length (segment or slice number). The method's feasibility was demonstrated at 7T for coverage of either a small slab or the near-whole brain at 0.8 mm isotropic resolution. Tissue contrast was found to be similar to that obtained with a state-of-art anatomical reference based on MP2RAGE. This MT-weighted EPI image allows an automatic reconstruction of the cortical surface to support laminar analysis in native fMRI space, obviating the need for distortion correction and registration.

Validating layer-specific VASO across species.

Cerebral blood volume (CBV) has been shown to be a robust and important physiological parameter for quantitative interpretation of functional (f)MRI, capable of delivering highly localized mapping of neural activity. Indeed, with recent advances in ultra-high-field (≥7T) MRI hardware and associated sequence libraries, it has become possible to capture non-invasive CBV weighted fMRI signals across cortical layers. One of the most widely used approaches to achieve this (in humans) is through vascular-space-occupancy (VASO) fMRI. Unfortunately, the exact contrast mechanisms of layer-dependent VASO fMRI have not been validated for human fMRI and thus interpretation of such data is confounded. Here we validate the signal source of layer-dependent SS-SI VASO fMRI using multi-modal imaging in a rat model in response to neuronal activation (somatosensory cortex) and respiratory challenge (hypercapnia). In particular VASO derived CBV measures are directly compared to concurrent measures of total haemoglobin changes from high resolution intrinsic optical imaging spectroscopy (OIS). Quantified cortical layer profiling is demonstrated to be in agreement between VASO and contrast enhanced fMRI (using monocrystalline iron oxide nanoparticles, MION). Responses show high spatial localisation to layers of cortical processing independent of confounding large draining veins which can hamper BOLD fMRI studies, (depending on slice positioning). Thus, a cross species comparison is enabled using VASO as a common measure. We find increased VASO based CBV reactivity (3.1 ± 1.2 fold increase) in humans compared to rats. Together, our findings confirm that the VASO contrast is indeed a reliable estimate of layer-specific CBV changes. This validation study increases the neuronal interpretability of human layer-dependent VASO fMRI as an appropriate method in neuroscience application studies, in which the presence of large draining intracortical and pial veins limits neuroscientific inference with BOLD fMRI.

LayNii: A software suite for layer-fMRI.

High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these high-resolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifacts, including image blurring, image distortions, low SNR, and restricted coverage. These challenges often result in insufficient spatial accuracy of conventional analysis pipelines. Here we introduce a new software suite that is specifically designed for layer-specific functional MRI: LayNii. This toolbox is a collection of command-line executable programs written in C/C++ and is distributed opensource and as pre-compiled binaries for Linux, Windows, and macOS. LayNii is designed for layer-fMRI data that suffer from SNR and coverage constraints and thus cannot be straightforwardly analyzed in alternative software packages. Some of the most popular programs of LayNii contain 'layerification' and columnarization in the native voxel space of functional data as well as many other layer-fMRI specific analysis tasks: layer-specific smoothing, model-based vein mitigation of GE-BOLD data, quality assessment of artifact dominated sub-millimeter fMRI, as well as analyses of VASO data.

Integrated VASO and perfusion contrast: A new tool for laminar functional MRI.

Earlier research in cats has shown that both cerebral blood volume (CBV) and cerebral blood flow (CBF) can be used to identify layer-dependent fMRI activation with spatial specificity superior to gradient-echo blood-oxygen-level-dependent (BOLD) contrast (Jin and Kim, 2008a). CBF contrast of perfusion fMRI at ultra-high field has not been widely applied in humans to measure laminar activity due to its low sensitivity, while CBV contrast for fMRI using vascular space occupancy (VASO) has been successfully used. However, VASO can be compromised by interference of blood in-flow effects and a temporally limited acquisition window around the blood-nulling time point. Here, we proposed to use DANTE (Delay Alternating with Nutation for Tailored Excitation) pulse trains combined with 3D-EPI to acquire an integrated VASO and perfusion (VAPER) contrast. The signal origin of the VAPER contrast was theoretically evaluated with respect to its CBV and CBF contributions using a four-compartment simulation model. The feasibility of VAPER to measure layer-dependent activity was empirically investigated in human primary motor cortex at 7 â€‹T. We demonstrated this new tool, with its highly specified functional layer profile, robust reproducibility, and improved sensitivity, to allow investigation of layer-specific cortical functions.

Sub-millimeter fMRI reveals multiple topographical digit representations that form action maps in human motor cortex.

The human brain coordinates a wide variety of motor activities. On a large scale, the cortical motor system is topographically organized such that neighboring body parts are represented by neighboring brain areas. This homunculus-like somatotopic organization along the central sulcus has been observed using neuroimaging for large body parts such as the face, hands and feet. However, on a finer scale, invasive electrical stimulation studies show deviations from this somatotopic organization that suggest an organizing principle based on motor actions rather than body part moved. It has not been clear how the action-map organization principle of the motor cortex in the mesoscopic (sub-millimeter) regime integrates into a body map organization principle on a macroscopic scale (cm). Here we developed and applied advanced mesoscopic (sub-millimeter) fMRI and analysis methodology to non-invasively investigate the functional organization topography across columnar and laminar structures in humans. Compared to previous methods, in this study, we could capture locally specific blood volume changes across entire brain regions along the cortical curvature. We find that individual fingers have multiple mirrored representations in the primary motor cortex depending on the movements they are involved in. We find that individual digits have cortical representations up to 3 â€‹mm apart from each other arranged in a column-like fashion. These representations are differentially engaged depending on whether the digits' muscles are used for different motor actions such as flexion movements, like grasping a ball or retraction movements like releasing a ball. This research provides a starting point for non-invasive investigation of mesoscale topography across layers and columns of the human cortex and bridges the gap between invasive electrophysiological investigations and large coverage non-invasive neuroimaging.

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

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.

Optimizing BOLD sensitivity in the 7T Human Connectome Project resting-state fMRI protocol using plug-and-play parallel transmission.

The Human Connectome Project (HCP) has a 7T component that aims to study the human brain's organization and function with high spatial and temporal resolution fMRI and diffusion-weighted acquisitions. For whole brain applications at 7T, a major weakness however remains the heterogeneity of the radiofrequency transmission field (B1+ ), which prevents from achieving an optimal signal and contrast homogeneously throughout the brain. In this work, we use parallel transmission (pTX) Universal Pulses (UP) to improve the flip angle homogeneity and demonstrate their application to highly accelerated multi-band EPI (MB5 and GRAPPA2, as prescribed in the 7T HCP protocol) sequence, but also to acquire at 7T B1+ -artefact-free T1 - and T2 -weighted anatomical scans used in the pre-processing pipeline of the HCP protocol. As compared to typical implementations of pTX, the proposed solution is fully operator-independent and allows "plug and play" exploitation of the benefits offered by multi-channel transmission. Validation in five healthy adults shows that the proposed technique achieves a flip angle homogeneity comparable to that of a clinical 3 T system. Compared to standard single-channel transmission, the use of UPs at 7T yielded up to a two-fold increase of the temporal signal-to-noise ratio in the temporal lobes as well as improved detection of functional connectivity in the brain regions most strongly affected by B1+ inhomogeneity.