Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Towards linking diffusion MRI based macro- and microstructure measures with cortico-cortical transmission in brain tumor patients.

We aimed to link macro- and microstructure measures of brain white matter obtained from diffusion MRI with effective connectivity measures based on a propagation of cortico-cortical evoked potentials induced with intrasurgical direct electrical stimulation. For this, we compared streamline lengths and log-transformed ratios of streamlines computed from presurgical diffusion-weighted images, and the delays and amplitudes of N1 peaks recorded intrasurgically with electrocorticography electrodes in a pilot study of 9 brain tumor patients. Our results showed positive correlation between these two modalities in the vicinity of the stimulation sites (Pearson coefficient 0.54±0.13 for N1 delays, and 0.47±0.23 for N1 amplitudes), which could correspond to the neural propagation via U-fibers. In addition, we reached high sensitivities (0.78±0.07) and very high specificities (0.93±0.03) in a binary variant of our comparison. Finally, we used the structural connectivity measures to predict the effective connectivity using a multiple linear regression model, and showed a significant role of brain microstructure-related indices in this relation.

On the generalizability of diffusion MRI signal representations across acquisition parameters, sequences and tissue types: Chronicles of the MEMENTO challenge.

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. The received submissions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.

Adaptive phase correction of diffusion-weighted images.

Phase correction (PC) is a preprocessing technique that exploits the phase of images acquired in Magnetic Resonance Imaging (MRI) to obtain real-valued images containing tissue contrast with additive Gaussian noise, as opposed to magnitude images which follow a non-Gaussian distribution, e.g. Rician. PC finds its natural application to diffusion-weighted images (DWIs) due to their inherent low signal-to-noise ratio and consequent non-Gaussianity that induces a signal overestimation bias that propagates to the calculated diffusion indices. PC effectiveness depends upon the quality of the phase estimation, which is often performed via a regularization procedure. We show that a suboptimal regularization can produce alterations of the true image contrast in the real-valued phase-corrected images. We propose adaptive phase correction (APC), a method where the phase is estimated by using MRI noise information to perform a complex-valued image regularization that accounts for the local variance of the noise. We show, on synthetic and acquired data, that APC leads to phase-corrected real-valued DWIs that present a reduced number of alterations and a reduced bias. The substantial absence of parameters for which human input is required favors a straightforward integration of APC in MRI processing pipelines.

White matter information flow mapping from diffusion MRI and EEG.

The human brain can be described as a network of specialized and spatially distributed regions. The activity of individual regions can be estimated using electroencephalography and the structure of the network can be measured using diffusion magnetic resonance imaging. However, the communication between the different cortical regions occurring through the white matter, coined information flow, cannot be observed by either modalities independently. Here, we present a new method to infer information flow in the white matter of the brain from joint diffusion MRI and EEG measurements. This is made possible by the millisecond resolution of EEG which makes the transfer of information from one region to another observable. A subject specific Bayesian network is built which captures the possible interactions between brain regions at different times. This network encodes the connections between brain regions detected using diffusion MRI tractography derived white matter bundles and their associated delays. By injecting the EEG measurements as evidence into this model, we are able to estimate the directed dynamical functional connectivity whose delays are supported by the diffusion MRI derived structural connectivity. We present our results in the form of information flow diagrams that trace transient communication between cortical regions over a functional data window. The performance of our algorithm under different noise levels is assessed using receiver operating characteristic curves on simulated data. In addition, using the well-characterized visual motor network as grounds to test our model, we present the information flow obtained during a reaching task following left or right visual stimuli. These promising results present the transfer of information from the eyes to the primary motor cortex. The information flow obtained using our technique can also be projected back to the anatomy and animated to produce videos of the information path through the white matter, opening a new window into multi-modal dynamic brain connectivity.

Reducing the number of samples in spatiotemporal dMRI acquisition design.

PURPOSE: Acquisition time is a major limitation in recovering brain white matter microstructure with diffusion magnetic resonance imaging. The aim of this paper is to bridge the gap between growing demands on spatiotemporal resolution of diffusion signal and the real-world time limitations. The authors introduce an acquisition scheme that reduces the number of samples under adjustable quality loss. METHODS: Finding a sampling scheme that maximizes signal quality and satisfies given time constraints is NP-hard. Therefore, a heuristic method based on genetic algorithm is proposed in order to find suboptimal solutions in acceptable time. The analyzed diffusion signal representation is defined in the qτ space, so that it captures both spacial and temporal phenomena. RESULTS: The experiments on synthetic data and in vivo diffusion images of the C57Bl6 wild-type mouse corpus callosum reveal superiority of the proposed approach over random sampling and even distribution in the qτ space. CONCLUSIONS: The use of genetic algorithm allows to find acquisition parameters that guarantee high signal reconstruction accuracy under given time constraints. In practice, the proposed approach helps to accelerate the acquisition for the use of qτ-dMRI signal representation.

Groupwise structural parcellation of the whole cortex: A logistic random effects model based approach.

Current theories hold that brain function is highly related to long-range physical connections through axonal bundles, namely extrinsic connectivity. However, obtaining a groupwise cortical parcellation based on extrinsic connectivity remains challenging. Current parcellation methods are computationally expensive; need tuning of several parameters or rely on ad-hoc constraints. Furthermore, none of these methods present a model for the cortical extrinsic connectivity of the cortex. To tackle these problems, we propose a parsimonious model for the extrinsic connectivity and an efficient parceling technique based on clustering of tractograms. Our technique allows the creation of single subject and groupwise parcellations of the whole cortex. The parcellations obtained with our technique are in agreement with structural and functional parcellations in the literature. In particular, the motor and sensory cortex are subdivided in agreement with the human homunculus of Penfield. We illustrate this by comparing our resulting parcels with the motor strip mapping included in the Human Connectome Project data.

AxTract: Toward microstructure informed tractography.

Diffusion-weighted (DW) magnetic resonance imaging (MRI) tractography has become the tool of choice to probe the human brain's white matter in vivo. However, tractography algorithms produce a large number of erroneous streamlines (false positives), largely due to complex ambiguous tissue configurations. Moreover, the relationship between the resulting streamlines and the underlying white matter microstructure characteristics remains poorly understood. In this work, we introduce a new approach to simultaneously reconstruct white matter fascicles and characterize the apparent distribution of axon diameters within fascicles. To achieve this, our method, AxTract, takes full advantage of the recent development DW-MRI microstructure acquisition, modeling, and reconstruction techniques. This enables AxTract to separate parallel fascicles with different microstructure characteristics, hence reducing ambiguities in areas of complex tissue configuration. We report a decrease in the incidence of erroneous streamlines compared to the conventional deterministic tractography algorithms on simulated data. We also report an average increase in streamline density over 15 known fascicles of the 34 healthy subjects. Our results suggest that microstructure information improves tractography in crossing areas of the white matter. Moreover, AxTract provides additional microstructure information along the fascicle that can be studied alongside other streamline-based indices. Overall, AxTract provides the means to distinguish and follow white matter fascicles using their microstructure characteristics, bringing new insights into the white matter organization. This is a step forward in microstructure informed tractography, paving the way to a new generation of algorithms able to deal with intricate configurations of white matter fibers and providing quantitative brain connectivity analysis. Hum Brain Mapp 38:5485-5500, 2017. © 2017 Wiley Periodicals, Inc.

Diffusion MRI microstructure models with in vivo human brain Connectome data: results from a multi-group comparison.

A large number of mathematical models have been proposed to describe the measured signal in diffusion-weighted (DW) magnetic resonance imaging (MRI). However, model comparison to date focuses only on specific subclasses, e.g. compartment models or signal models, and little or no information is available in the literature on how performance varies among the different types of models. To address this deficiency, we organized the 'White Matter Modeling Challenge' during the International Symposium on Biomedical Imaging (ISBI) 2015 conference. This competition aimed to compare a range of different kinds of models in their ability to explain a large range of measurable in vivo DW human brain data. Specifically, we assessed the ability of models to predict the DW signal accurately for new diffusion gradients and b values. We did not evaluate the accuracy of estimated model parameters, as a ground truth is hard to obtain. We used the Connectome scanner at the Massachusetts General Hospital, using gradient strengths of up to 300 mT/m and a broad set of diffusion times. We focused on assessing the DW signal prediction in two regions: the genu in the corpus callosum, where the fibres are relatively straight and parallel, and the fornix, where the configuration of fibres is more complex. The challenge participants had access to three-quarters of the dataset and their models were ranked on their ability to predict the remaining unseen quarter of the data. The challenge provided a unique opportunity for a quantitative comparison of diverse methods from multiple groups worldwide. The comparison of the challenge entries reveals interesting trends that could potentially influence the next generation of diffusion-based quantitative MRI techniques. The first is that signal models do not necessarily outperform tissue models; in fact, of those tested, tissue models rank highest on average. The second is that assuming a non-Gaussian (rather than purely Gaussian) noise model provides little improvement in prediction of unseen data, although it is possible that this may still have a beneficial effect on estimated parameter values. The third is that preprocessing the training data, here by omitting signal outliers, and using signal-predicting strategies, such as bootstrapping or cross-validation, could benefit the model fitting. The analysis in this study provides a benchmark for other models and the data remain available to build up a more complete comparison in the future.

MAPL: Tissue microstructure estimation using Laplacian-regularized MAP-MRI and its application to HCP data.

The recovery of microstructure-related features of the brain's white matter is a current challenge in diffusion MRI. To robustly estimate these important features from multi-shell diffusion MRI data, we propose to analytically regularize the coefficient estimation of the Mean Apparent Propagator (MAP)-MRI method using the norm of the Laplacian of the reconstructed signal. We first compare our approach, which we call MAPL, with competing, state-of-the-art functional basis approaches. We show that it outperforms the original MAP-MRI implementation and the recently proposed modified Spherical Polar Fourier (mSPF) basis with respect to signal fitting and reconstruction of the Ensemble Average Propagator (EAP) and Orientation Distribution Function (ODF) in noisy, sparsely sampled data of a physical phantom with reference gold standard data. Then, to reduce the variance of parameter estimation using multi-compartment tissue models, we propose to use MAPL's signal fitting and extrapolation as a preprocessing step. We study the effect of MAPL on the estimation of axon diameter using a simplified Axcaliber model and axonal dispersion using the Neurite Orientation Dispersion and Density Imaging (NODDI) model. We show the positive effect of using it as a preprocessing step in estimating and reducing the variances of these parameters in the Corpus Callosum of six different subjects of the MGH Human Connectome Project. Finally, we correlate the estimated axon diameter, dispersion and restricted volume fractions with Fractional Anisotropy (FA) and clearly show that changes in FA significantly correlate with changes in all estimated parameters. Overall, we illustrate the potential of using a well-regularized functional basis together with multi-compartment approaches to recover important microstructure tissue parameters with much less variability, thus contributing to the challenge of better understanding microstructure-related features of the brain's white matter.

Comparison of sampling strategies and sparsifying transforms to improve compressed sensing diffusion spectrum imaging.

PURPOSE: Diffusion Spectrum Imaging enables to reconstruct the ensemble average propagator (EAP) at the expense of having to acquire a large number of measurements. Compressive sensing offers an efficient way to decrease the required number of measurements. The purpose of this work is to perform a thorough experimental comparison of three sampling strategies and six sparsifying transforms to show their impact when applied to accelerate compressive sensing-diffusion spectrum imaging. METHODS: We propose a novel sampling scheme that assures uniform angular and random radial q-space samples. We also compare and implement six discrete sparse representations of the EAP and thoroughly evaluate them on synthetic and real data using metrics from the full EAP, kurtosis, and orientation distribution function. RESULTS: The discrete wavelet transform with Cohen-Daubechies-Feauveau 9/7 wavelets and uniform angular sampling in combination with random radial sampling showed to be better than other tested techniques to accurately reconstruct the EAP and its features. CONCLUSION: It is important to jointly optimize the sampling scheme and the sparsifying transform to obtain accelerated compressive sensing-diffusion spectrum imaging. Experiments on synthetic and real human brain data show that one can robustly recover both radial and angular EAP features while undersampling the acquisition to 64 measurements (undersampling factor of 4).

Towards quantitative connectivity analysis: reducing tractography biases.

Diffusion MRI tractography is often used to estimate structural connections between brain areas and there is a fast-growing interest in quantifying these connections based on their position, shape, size and length. However, a portion of the connections reconstructed with tractography is biased by their position, shape, size and length. Thus, connections reconstructed are not equally distributed in all white matter bundles. Quantitative measures of connectivity based on the streamline distribution in the brain such as streamline count (density), average length and spatial extent (volume) are biased by erroneous streamlines produced by tractography algorithms. In this paper, solutions are proposed to reduce biases in the streamline distribution. First, we propose to optimize tractography parameters in terms of connectivity. Then, we propose to relax the tractography stopping criterion with a novel probabilistic stopping criterion and a particle filtering method, both based on tissue partial volume estimation maps calculated from a T1-weighted image. We show that optimizing tractography parameters, stopping and seeding strategies can reduce the biases in position, shape, size and length of the streamline distribution. These tractography biases are quantitatively reported using in-vivo and synthetic data. This is a critical step towards producing tractography results for quantitative structural connectivity analysis.

Non-Negative Spherical Deconvolution (NNSD) for estimation of fiber Orientation Distribution Function in single-/multi-shell diffusion MRI.

Spherical Deconvolution (SD) is commonly used for estimating fiber Orientation Distribution Functions (fODFs) from diffusion-weighted signals. Existing SD methods can be classified into two categories: 1) Continuous Representation based SD (CR-SD), where typically Spherical Harmonic (SH) representation is used for convenient analytical solutions, and 2) Discrete Representation based SD (DR-SD), where the signal profile is represented by a discrete set of basis functions uniformly oriented on the unit sphere. A feasible fODF should be non-negative and should integrate to unity throughout the unit sphere S(2). However, to our knowledge, most existing SH-based SD methods enforce non-negativity only on discretized points and not the whole continuum of S(2). Maximum Entropy SD (MESD) and Cartesian Tensor Fiber Orientation Distributions (CT-FOD) are the only SD methods that ensure non-negativity throughout the unit sphere. They are however computational intensive and are susceptible to errors caused by numerical spherical integration. Existing SD methods are also known to overestimate the number of fiber directions, especially in regions with low anisotropy. DR-SD introduces additional error in peak detection owing to the angular discretization of the unit sphere. This paper proposes a SD framework, called Non-Negative SD (NNSD), to overcome all the limitations above. NNSD is significantly less susceptible to the false-positive peaks, uses SH representation for efficient analytical spherical deconvolution, and allows accurate peak detection throughout the whole unit sphere. We further show that NNSD and most existing SD methods can be extended to work on multi-shell data by introducing a three-dimensional fiber response function. We evaluated NNSD in comparison with Constrained SD (CSD), a quadratic programming variant of CSD, MESD, and an L1-norm regularized non-negative least-squares DR-SD. Experiments on synthetic and real single-/multi-shell data indicate that NNSD improves estimation performance in terms of mean difference of angles, peak detection consistency, and anisotropy contrast between isotropic and anisotropic regions.

Constrained diffusion kurtosis imaging using ternary quartics & MLE.

PURPOSE: Diffusion kurtosis imaging (DKI) is a recent improvement over diffusion tensor imaging that characterizes tissue by quantifying non-gaussian diffusion using a 3D fourth-order kurtosis tensor. DKI needs to consider three constraints to be physically relevant. Further, it can be improved by considering the Rician signal noise model. A DKI estimation method is proposed that considers all three constraints correctly, accounts for the signal noise and incorporates efficient gradient-based optimization to improve over existing methods. METHODS: The ternary quartic parameterization is utilized to elegantly impose the positivity of the kurtosis tensor implicitly. Sequential quadratic programming with analytical gradients is employed to solve nonlinear constrained optimization efficiently. Finally, a maximum likelihood estimator based on Rician distribution is considered to account for signal noise. RESULTS: Extensive experiments conducted on synthetic data verify a MATLAB implementation by showing dramatically improved performance in terms of estimation time and quality. Experiments on in vivo cerebral data confirm that in practice the proposed method can obtain improved results. CONCLUSION: The proposed ternary quartic-based approach with a gradient-based optimization scheme and maximum likelihood estimator for constrained DKI estimation improves considerably on existing DKI methods.

A robust variational approach for simultaneous smoothing and estimation of DTI.

Estimating diffusion tensors is an essential step in many applications - such as diffusion tensor image (DTI) registration, segmentation and fiber tractography. Most of the methods proposed in the literature for this task are not simultaneously statistically robust and feature preserving techniques. In this paper, we propose a novel and robust variational framework for simultaneous smoothing and estimation of diffusion tensors from diffusion MRI. Our variational principle makes use of a recently introduced total Kullback-Leibler (tKL) divergence for DTI regularization. tKL is a statistically robust dissimilarity measure for diffusion tensors, and regularization by using tKL ensures the symmetric positive definiteness of tensors automatically. Further, the regularization is weighted by a non-local factor adapted from the conventional non-local means filters. Finally, for the data fidelity, we use the nonlinear least-squares term derived from the Stejskal-Tanner model. We present experimental results depicting the positive performance of our method in comparison to competing methods on synthetic and real data examples.

Design of multishell sampling schemes with uniform coverage in diffusion MRI.

PURPOSE: In diffusion MRI, a technique known as diffusion spectrum imaging reconstructs the propagator with a discrete Fourier transform, from a Cartesian sampling of the diffusion signal. Alternatively, it is possible to directly reconstruct the orientation distribution function in q-ball imaging, providing so-called high angular resolution diffusion imaging. In between these two techniques, acquisitions on several spheres in q-space offer an interesting trade-off between the angular resolution and the radial information gathered in diffusion MRI. A careful design is central in the success of multishell acquisition and reconstruction techniques. METHODS: The design of acquisition in multishell is still an open and active field of research, however. In this work, we provide a general method to design multishell acquisition with uniform angular coverage. This method is based on a generalization of electrostatic repulsion to multishell. RESULTS: We evaluate the impact of our method using simulations, on the angular resolution in one and two bundles of fiber configurations. Compared to more commonly used radial sampling, we show that our method improves the angular resolution, as well as fiber crossing discrimination. DISCUSSION: We propose a novel method to design sampling schemes with optimal angular coverage and show the positive impact on angular resolution in diffusion MRI.

Identifying subcortical connectivity during brain tumor surgery: a multimodal study.

Bipolar direct electrical stimulation (DES) of an awake patient is the reference technique for identifying brain structures to achieve maximal safe tumor resection. Unfortunately, DES cannot be performed in all cases. Alternative surgical tools are, therefore, needed to aid identification of subcortical connectivity during brain tumor removal. In this pilot study, we sought to (i) evaluate the combined use of evoked potential (EP) and tractography for identification of white matter (WM) tracts under the functional control of DES, and (ii) provide clues to the electrophysiological effects of bipolar stimulation on neural pathways. We included 12 patients (mean age of 38.4 years) who had had a dMRI-based tractography and a functional brain mapping under awake craniotomy for brain tumor removal. Electrophysiological recordings of subcortical evoked potentials (SCEPs) were acquired during bipolar low frequency (2 Hz) stimulation of the WM functional sites identified during brain mapping. SCEPs were successfully triggered in 11 out of 12 patients. The median length of the stimulated fibers was 43.24 ± 19.55 mm, belonging to tracts of median lengths of 89.84 ± 24.65 mm. The electrophysiological (delay, amplitude, and speed of propagation) and structural (number and lengths of streamlines, and mean fractional anisotropy) measures were correlated. In our experimental conditions, SCEPs were essentially limited to a subpart of the bundles, suggesting a selectivity of action of the DES on the brain networks. Correlations between functional, structural, and electrophysiological measures portend the combined use of EPs and tractography as a potential intraoperative tool to achieve maximum safe resection in brain tumor surgery.

A Riemannian Revisiting of Structure-Function Mapping Based on Eigenmodes.

Understanding the link between brain structure and function may not only improve our knowledge of brain organization, but also lead to better quantification of pathology. To quantify this link, recent studies have attempted to predict the brain's functional connectivity from its structural connectivity. However, functional connectivity matrices live in the Riemannian manifold of the symmetric positive definite space and a specific attention must be paid to operate on this appropriate space. In this work we investigated the implications of using a distance based on an affine invariant Riemannian metric in the context of structure-function mapping. Specifically, we revisit previously proposed structure-function mappings based on eigendecomposition and test them on 100 healthy subjects from the Human Connectome Project using this adapted notion of distance. First, we show that using this Riemannian distance significantly alters the notion of similarity between subjects from a functional point of view. We also show that using this distance improves the correlation between the structural and functional similarity of different subjects. Finally, by using a distance appropriate to this manifold, we demonstrate the importance of mapping function from structure under the Riemannian manifold and show in particular that it is possible to outperform the group average and the so-called glass ceiling on the performance of mappings based on eigenmodes.

An Anisotropic 4D Filtering Approach to Recover Brain Activation From Paradigm-Free Functional MRI Data.

Context: Functional Magnetic Resonance Imaging (fMRI) is a non-invasive imaging technique that provides an indirect view into brain activity via the blood oxygen level dependent (BOLD) response. In particular, resting-state fMRI poses challenges to the recovery of brain activity without prior knowledge on the experimental paradigm, as it is the case for task fMRI. Conventional methods to infer brain activity from the fMRI signals, for example, the general linear model (GLM), require the knowledge of the experimental paradigm to define regressors and estimate the contribution of each voxel's time course to the task. To overcome this limitation, approaches to deconvolve the BOLD response and recover the underlying neural activations without a priori information on the task have been proposed. State-of-the-art techniques, and in particular the total activation (TA), formulate the deconvolution as an optimization problem with decoupled spatial and temporal regularization and an optimization strategy that alternates between the constraints. Approach: In this work, we propose a paradigm-free regularization algorithm named Anisotropic 4D-fMRI (A4D-fMRI) that is applied on the 4D fMRI image, acting simultaneously in the 3D space and 1D time dimensions. Based on the idea that large image variations should be preserved as they occur during brain activations, whereas small variations considered as noise should be removed, the A4D-fMRI applies an anisotropic regularization, thus recovering the location and the duration of brain activations. Results: Using the experimental paradigm as ground truth, the A4D-fMRI is validated on synthetic and real task-fMRI data from 51 subjects, and its performance is compared to the TA. Results show higher correlations of the recovered time courses with the ground truth compared to the TA and lower computational times. In addition, we show that the A4D-fMRI recovers activity that agrees with the GLM, without requiring or using any knowledge of the experimental paradigm.

DORIS: A diffusion MRI-based 10 tissue class deep learning segmentation algorithm tailored to improve anatomically-constrained tractography.

Modern tractography algorithms such as anatomically-constrained tractography (ACT) are based on segmentation maps of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). These maps are generally estimated from a T1-weighted (T1w) image and then registered in diffusion weighted images (DWI) space. Registration of T1w to diffusion space and partial volume estimation are challenging and rarely voxel-perfect. Diffusion-based segmentation would, thus, potentially allow not to have higher quality anatomical priors injected in the tractography process. On the other hand, even if FA-based tractography is possible without T1 registration, the literature shows that this technique suffers from multiple issues such as holes in the tracking mask and a high proportion of generated broken and anatomically implausible streamlines. Therefore, there is an important need for a tissue segmentation algorithm that works directly in the native diffusion space. We propose DORIS, a DWI-based deep learning segmentation algorithm. DORIS outputs 10 different tissue classes including WM, GM, CSF, ventricles, and 6 other subcortical structures (putamen, pallidum, hippocampus, caudate, amygdala, and thalamus). DORIS was trained and validated on a wide range of subjects, including 1,000 individuals from 22 to 90 years old from clinical and research DWI acquisitions, from 5 public databases. In the absence of a "true" ground truth in diffusion space, DORIS used a silver standard strategy from Freesurfer output registered onto the DWI. This strategy is extensively evaluated and discussed in the current study. Segmentation maps provided by DORIS are quantitatively compared to Freesurfer and FSL-fast and the impacts on tractography are evaluated. Overall, we show that DORIS is fast, accurate, and reproducible and that DORIS-based tractograms produce bundles with a longer mean length and fewer anatomically implausible streamlines.