Connectome spectrum electromagnetic tomography: A method to reconstruct electrical brain source networks at high-spatial resolution.

Connectome spectrum electromagnetic tomography (CSET) combines diffusion MRI-derived structural connectivity data with well-established graph signal processing tools to solve the M/EEG inverse problem. Using simulated EEG signals from fMRI responses, and two EEG datasets on visual-evoked potentials, we provide evidence supporting that (i) CSET captures realistic neurophysiological patterns with better accuracy than state-of-the-art methods, (ii) CSET can reconstruct brain responses more accurately and with more robustness to intrinsic noise in the EEG signal. These results demonstrate that CSET offers high spatio-temporal accuracy, enabling neuroscientists to extend their research beyond the current limitations of low sampling frequency in functional MRI and the poor spatial resolution of M/EEG.

Towards Automated Brain Aneurysm Detection in TOF-MRA: Open Data, Weak Labels, and Anatomical Knowledge.

Brain aneurysm detection in Time-Of-Flight Magnetic Resonance Angiography (TOF-MRA) has undergone drastic improvements with the advent of Deep Learning (DL). However, performances of supervised DL models heavily rely on the quantity of labeled samples, which are extremely costly to obtain. Here, we present a DL model for aneurysm detection that overcomes the issue with "weak" labels: oversized annotations which are considerably faster to create. Our weak labels resulted to be four times faster to generate than their voxel-wise counterparts. In addition, our model leverages prior anatomical knowledge by focusing only on plausible locations for aneurysm occurrence. We first train and evaluate our model through cross-validation on an in-house TOF-MRA dataset comprising 284 subjects (170 females / 127 healthy controls / 157 patients with 198 aneurysms). On this dataset, our best model achieved a sensitivity of 83%, with False Positive (FP) rate of 0.8 per patient. To assess model generalizability, we then participated in a challenge for aneurysm detection with TOF-MRA data (93 patients, 20 controls, 125 aneurysms). On the public challenge, sensitivity was 68% (FP rate = 2.5), ranking 4th/18 on the open leaderboard. We found no significant difference in sensitivity between aneurysm risk-of-rupture groups (p = 0.75), locations (p = 0.72), or sizes (p = 0.15). Data, code and model weights are released under permissive licenses. We demonstrate that weak labels and anatomical knowledge can alleviate the necessity for prohibitively expensive voxel-wise annotations.

Structure supports function: Informing directed and dynamic functional connectivity with anatomical priors.

The dynamic repertoire of functional brain networks is constrained by the underlying topology of structural connections. Despite this intrinsic relationship between structural connectivity (SC) and functional connectivity (FC), integrative and multimodal approaches to combine the two remain limited. Here, we propose a new adaptive filter for estimating dynamic and directed FC using structural connectivity information as priors. We tested the filter in rat epicranial recordings and human event-related EEG data, using SC priors from a meta-analysis of tracer studies and diffusion tensor imaging metrics, respectively. We show that, particularly under conditions of low signal-to-noise ratio, SC priors can help to refine estimates of directed FC, promoting sparse functional networks that combine information from structure and function. In addition, the proposed filter provides intrinsic protection against SC-related false negatives, as well as robustness against false positives, representing a valuable new tool for multimodal imaging in the context of dynamic and directed FC analysis.

A Fetal Brain magnetic resonance Acquisition Numerical phantom (FaBiAN).

Accurate characterization of in utero human brain maturation is critical as it involves complex and interconnected structural and functional processes that may influence health later in life. Magnetic resonance imaging is a powerful tool to investigate equivocal neurological patterns during fetal development. However, the number of acquisitions of satisfactory quality available in this cohort of sensitive subjects remains scarce, thus hindering the validation of advanced image processing techniques. Numerical phantoms can mitigate these limitations by providing a controlled environment with a known ground truth. In this work, we present FaBiAN, an open-source Fetal Brain magnetic resonance Acquisition Numerical phantom that simulates clinical T2-weighted fast spin echo sequences of the fetal brain. This unique tool is based on a general, flexible and realistic setup that includes stochastic fetal movements, thus providing images of the fetal brain throughout maturation comparable to clinical acquisitions. We demonstrate its value to evaluate the robustness and optimize the accuracy of an algorithm for super-resolution fetal brain magnetic resonance imaging from simulated motion-corrupted 2D low-resolution series compared to a synthetic high-resolution reference volume. We also show that the images generated can complement clinical datasets to support data-intensive deep learning methods for fetal brain tissue segmentation.

A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials.

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

Source imaging of high-density visual evoked potentials with multi-scale brain parcellations and connectomes.

We describe the multimodal neuroimaging dataset VEPCON (OpenNeuro Dataset ds003505). It includes raw data and derivatives of high-density EEG, structural MRI, diffusion weighted images (DWI) and single-trial behavior (accuracy, reaction time). Visual evoked potentials (VEPs) were recorded while participants (n = 20) discriminated briefly presented faces from scrambled faces, or coherently moving stimuli from incoherent ones. EEG and MRI were recorded separately from the same participants. The dataset contains raw EEG and behavioral data, pre-processed EEG of single trials in each condition, structural MRIs, individual brain parcellations at 5 spatial resolutions (83 to 1015 regions), and the corresponding structural connectomes computed from fiber count, fiber density, average fractional anisotropy and mean diffusivity maps. For source imaging, VEPCON provides EEG inverse solutions based on individual anatomy, with Python and Matlab scripts to derive activity time-series in each brain region, for each parcellation level. The BIDS-compatible dataset can contribute to multimodal methods development, studying structure-function relations, and to unimodal optimization of source imaging and graph analyses, among many other possibilities.

The connectome spectrum as a canonical basis for a sparse representation of fast brain activity.

The functional organization of neural processes is constrained by the brain's intrinsic structural connectivity, i.e., the connectome. Here, we explore how structural connectivity can improve the representation of brain activity signals and their dynamics. Using a multi-modal imaging dataset (electroencephalography, structural MRI, and diffusion MRI), we represent electrical brain activity at the cortical surface as a time-varying composition of harmonic modes of structural connectivity. These harmonic modes are known as connectome harmonics. Here we describe brain activity signal as a time-varying combination of connectome harmonics. We term this description as the connectome spectrum of the signal. We found that: first, the brain activity signal is represented more compactly by the connectome spectrum than by the traditional area-based representation; second, the connectome spectrum characterizes fast brain dynamics in terms of signal broadcasting profile, revealing different temporal regimes of integration and segregation that are consistent across participants. And last, the connectome spectrum characterizes fast brain dynamics with fewer degrees of freedom than area-based signal representations. Specifically, we show that a smaller number of dimensions capture the differences between low-level and high-level visual processing in the connectome spectrum. Also, we demonstrate that connectome harmonics capture more sensitively the topological properties of brain activity. In summary, this work provides statistical, functional, and topological evidence indicating that the description of brain activity in terms of structural connectivity fosters a more comprehensive understanding of large-scale dynamic neural functioning.

Fetal Brain Biometric Measurements on 3D Super-Resolution Reconstructed T2-Weighted MRI: An Intra- and Inter-observer Agreement Study.

We present the comparison of two-dimensional (2D) fetal brain biometry on magnetic resonance (MR) images using orthogonal 2D T2-weighted sequences (T2WSs) vs. one 3D super-resolution (SR) reconstructed volume and evaluation of the level of confidence and concordance between an experienced pediatric radiologist (obs1) and a junior radiologist (obs2). Twenty-five normal fetal brain MRI scans (18-34 weeks of gestation) including orthogonal 3-mm-thick T2WSs were analyzed retrospectively. One 3D SR volume was reconstructed per subject based on multiple series of T2WSs. The two observers performed 11 2D biometric measurements (specifying their level of confidence) on T2WS and SR volumes. Measurements were compared using the paired Wilcoxon rank sum test between observers for each dataset (T2WS and SR) and between T2WS and SR for each observer. Bland-Altman plots were used to assess the agreement between each pair of measurements. Measurements were made with low confidence in three subjects by obs1 and in 11 subjects by obs2 (mostly concerning the length of the corpus callosum on T2WS). Inter-rater intra-dataset comparisons showed no significant difference (p > 0.05), except for brain axial biparietal diameter (BIP) on T2WS and for brain and skull coronal BIP and coronal transverse cerebellar diameter (DTC) on SR. None of them remained significant after correction for multiple comparisons. Inter-dataset intra-rater comparisons showed statistical differences in brain axial and coronal BIP for both observers, skull coronal BIP for obs1, and axial and coronal DTC for obs2. After correction for multiple comparisons, only axial brain BIP remained significantly different, but differences were small (2.95 ± 1.73 mm). SR allows similar fetal brain biometry as compared to using the conventional T2WS while improving the level of confidence in the measurements and using a single reconstructed volume.

High-density Electric Source Imaging of interictal epileptic discharges: How many electrodes and which time point?

OBJECTIVE: To assess the value of caudal EEG electrodes over cheeks and neck for high-density electric source imaging (ESI) in presurgical epilepsy evaluation, and to identify the best time point during averaged interictal epileptic discharges (IEDs) for optimal ESI accuracy. METHODS: We retrospectively examined presurgical 257-channel EEG recordings of 45 patients with pharmacoresistant focal epilepsy. By stepwise removal of cheek and neck electrodes, averaged IEDs were downsampled to 219, 204, and 156 EEG channels. Additionally, ESI at the IED's half-rise was compared to other time points. The respective sources of maximum activity were compared to the resected brain area and postsurgical outcome. RESULTS: Caudal channels had disproportionately more artefacts. In 30 patients with favourable outcome, the 204-channel array yielded the most accurate results with ESI maxima < 10 mm from the resection in 67% and inside affected sublobes in 83%. Neither in temporal nor in extratemporal cases did the full 257-channel setup improve ESI accuracy. ESI was most accurate at 50% of the IED's rising phase. CONCLUSION: Information from cheeks and neck electrodes did not improve high-density ESI accuracy, probably due to higher artefact load and suboptimal biophysical modelling. SIGNIFICANCE: Very caudal EEG electrodes should be used for ESI with caution.

Using structural connectivity to augment community structure in EEG functional connectivity.

Recently, EEG recording techniques and source analysis have improved, making it feasible to tap into fast network dynamics. Yet, analyzing whole-cortex EEG signals in source space is not standard, partly because EEG suffers from volume conduction: Functional connectivity (FC) reflecting genuine functional relationships is impossible to disentangle from spurious FC introduced by volume conduction. Here, we investigate the relationship between white matter structural connectivity (SC) and large-scale network structure encoded in EEG-FC. We start by confirming that FC (power envelope correlations) is predicted by SC beyond the impact of Euclidean distance, in line with the assumption that SC mediates genuine FC. We then use information from white matter structural connectivity in order to smooth the EEG signal in the space spanned by graphs derived from SC. Thereby, FC between nearby, structurally connected brain regions increases while FC between nonconnected regions remains unchanged, resulting in an increase in genuine, SC-mediated FC. We analyze the induced changes in FC, assessing the resemblance between EEG-FC and volume-conduction- free fMRI-FC, and find that smoothing increases resemblance in terms of overall correlation and community structure. This result suggests that our method boosts genuine FC, an outcome that is of interest for many EEG network neuroscience questions.

Connectome spectral analysis to track EEG task dynamics on a subsecond scale.

We present an approach for tracking fast spatiotemporal cortical dynamics in which we combine white matter connectivity data with source-projected electroencephalographic (EEG) data. We employ the mathematical framework of graph signal processing in order to derive the Fourier modes of the brain structural connectivity graph, or "network harmonics". These network harmonics are naturally ordered by smoothness. Smoothness in this context can be understood as the amount of variation along the cortex, leading to a multi-scale representation of brain connectivity. We demonstrate that network harmonics provide a sparse representation of the EEG signal, where, at certain times, the smoothest 15 network harmonics capture 90% of the signal power. This suggests that network harmonics are functionally meaningful, which we demonstrate by using them as a basis for the functional EEG data recorded from a face detection task. There, only 13 network harmonics are sufficient to track the large-scale cortical activity during the processing of the stimuli with a 50 â€‹ms resolution, reproducing well-known activity in the fusiform face area as well as revealing co-activation patterns in somatosensory/motor and frontal cortices that an unconstrained ROI-by-ROI analysis fails to capture. The proposed approach is simple and fast, provides a means of integration of multimodal datasets, and is tied to a theoretical framework in mathematics and physics. Thus, network harmonics point towards promising research directions both theoretically - for example in exploring the relationship between structure and function in the brain - and practically - for example for network tracking in different tasks and groups of individuals, such as patients.

Abnormal directed connectivity of resting state networks in focal epilepsy.

OBJECTIVE: Epilepsy diagnosis can be difficult in the absence of interictal epileptic discharges (IED) on scalp EEG. We used high-density EEG to measure connectivity in large-scale functional networks of patients with focal epilepsy (Temporal and Extratemporal Lobe Epilepsy, TLE and ETLE) and tested for network alterations during resting wakefulness without IEDs, compared to healthy controls. We measured global efficiency as a marker of integration within networks. METHODS: We analysed 49 adult patients with focal epilepsy and 16 healthy subjects who underwent high-density-EEG and structural MRI. We estimated cortical activity using electric source analysis in 82 atlas-based cortical regions based on the individual MRI. We applied directed connectivity analysis (Partial Directed Coherence) on these sources and performed graph analysis: we computed the Global Efficiency on the whole brain and on each resting state network. We tested these features in different group of patients. RESULTS: Compared to controls, efficiency was increased in both TLE and ETLE (p < 0.05). The somato-motor-network, the ventral-attention-network and the default-mode-network had a significantly increased efficiency (p < 0.05) in both TLE and ETLE as well as TLE with hippocampal sclerosis. SIGNIFICANCE: During interictal scalp EEG epochs without IED, patients with focal epilepsy show brain functional connectivity alterations in the whole brain and in specific resting-state-networks. This higher integration reflects a chronic effect of pathological activity within these structures and complement previous work on altered information outflow. These findings could increase the diagnostic sensitivity of scalp EEG to identify epileptic activity in the absence of IED.

Automated template-based brain localization and extraction for fetal brain MRI reconstruction.

Most fetal brain MRI reconstruction algorithms rely only on brain tissue-relevant voxels of low-resolution (LR) images to enhance the quality of inter-slice motion correction and image reconstruction. Consequently the fetal brain needs to be localized and extracted as a first step, which is usually a laborious and time consuming manual or semi-automatic task. We have proposed in this work to use age-matched template images as prior knowledge to automatize brain localization and extraction. This has been achieved through a novel automatic brain localization and extraction method based on robust template-to-slice block matching and deformable slice-to-template registration. Our template-based approach has also enabled the reconstruction of fetal brain images in standard radiological anatomical planes in a common coordinate space. We have integrated this approach into our new reconstruction pipeline that involves intensity normalization, inter-slice motion correction, and super-resolution (SR) reconstruction. To this end we have adopted a novel approach based on projection of every slice of the LR brain masks into the template space using a fusion strategy. This has enabled the refinement of brain masks in the LR images at each motion correction iteration. The overall brain localization and extraction algorithm has shown to produce brain masks that are very close to manually drawn brain masks, showing an average Dice overlap measure of 94.5%. We have also demonstrated that adopting a slice-to-template registration and propagation of the brain mask slice-by-slice leads to a significant improvement in brain extraction performance compared to global rigid brain extraction and consequently in the quality of the final reconstructed images. Ratings performed by two expert observers show that the proposed pipeline can achieve similar reconstruction quality to reference reconstruction based on manual slice-by-slice brain extraction. The proposed brain mask refinement and reconstruction method has shown to provide promising results in automatic fetal brain MRI segmentation and volumetry in 26 fetuses with gestational age range of 23 to 38 weeks.

An efficient total variation algorithm for super-resolution in fetal brain MRI with adaptive regularization.

Although fetal anatomy can be adequately viewed in new multi-slice MR images, many critical limitations remain for quantitative data analysis. To this end, several research groups have recently developed advanced image processing methods, often denoted by super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) images, a high-resolution (HR) motion-free volume. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has been quite attracted by Total Variation energies because of their ability in edge preserving but only standard explicit steepest gradient techniques have been applied for optimization. In a preliminary work, it has been shown that novel fast convex optimization techniques could be successfully applied to design an efficient Total Variation optimization algorithm for the super-resolution problem. In this work, two major contributions are presented. Firstly, we will briefly review the Bayesian and Variational dual formulations of current state-of-the-art methods dedicated to fetal MRI reconstruction. Secondly, we present an extensive quantitative evaluation of our SR algorithm previously introduced on both simulated fetal and real clinical data (with both normal and pathological subjects). Specifically, we study the robustness of regularization terms in front of residual registration errors and we also present a novel strategy for automatically select the weight of the regularization as regards the data fidelity term. Our results show that our TV implementation is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods.

Efficient total variation algorithm for fetal brain MRI reconstruction.

Fetal MRI reconstruction aims at finding a high-resolution image given a small set of low-resolution images. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has considered several regularization terms s.a. Dirichlet/Laplacian energy, Total Variation (TV)- based energies and more recently non-local means. Although TV energies are quite attractive because of their ability in edge preservation, standard explicit steepest gradient techniques have been applied to optimize fetal-based TV energies. The main contribution of this work lies in the introduction of a well-posed TV algorithm from the point of view of convex optimization. Specifically, our proposed TV optimization algorithm or fetal reconstruction is optimal w.r.t. the asymptotic and iterative convergence speeds O(1/n2) and O(1/√ε), while existing techniques are in O(1/n2) and O(1/√ε). We apply our algorithm to (1) clinical newborn data, considered as ground truth, and (2) clinical fetal acquisitions. Our algorithm compares favorably with the literature in terms of speed and accuracy.