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.

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.

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.

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.

A unified framework for multimodal structure-function mapping based on eigenmodes.

Characterizing the connection between brain structure and brain function is essential for understanding how behaviour emerges from the underlying anatomy. A number of studies have shown that the network structure of the white matter shapes functional connectivity. Therefore, it should be possible to predict, at least partially, functional connectivity given the structural network. Many structure-function mappings have been proposed in the literature, including several direct mappings between the structural and functional connectivity matrices. However, the current literature is fragmented and does not provide a uniform treatment of current methods based on eigendecompositions. In particular, existing methods have never been compared to each other and their relationship explicitly derived in the context of brain structure-function mapping. In this work, we propose a unified computational framework that generalizes recently proposed structure-function mappings based on eigenmodes. Using this unified framework, we highlight the link between existing models and show how they can be obtained by specific choices of the parameters of our framework. By applying our framework to 50 subjects of the Human Connectome Project, we reproduce 6 recently published results, devise two new models and provide a direct comparison between all mappings. Finally, we show that a glass ceiling on the performance of mappings based on eigenmodes seems to be reached and conclude with possible approaches to break this performance limit.

A computational Framework for generating rotation invariant features and its application in diffusion MRI.

In this work, we present a novel computational framework for analytically generating a complete set of algebraically independent Rotation Invariant Features (RIF) given the Laplace-series expansion of a spherical function. Our computational framework provides a closed-form solution for these new invariants, which are the natural expansion of the well known spherical mean, power-spectrum and bispectrum invariants. We highlight the maximal number of algebraically independent invariants which can be obtained from a truncated Spherical Harmonic (SH) representation of a spherical function and show that most of these new invariants can be linked to statistical and geometrical measures of spherical functions, such as the mean, the variance and the volume of the spherical signal. Moreover, we demonstrate their application to dMRI signal modeling including the Apparent Diffusion Coefficient (ADC), the diffusion signal and the fiber Orientation Distribution Function (fODF). In addition, using both synthetic and real data, we test the ability of our invariants to estimate brain tissue microstructure in healthy subjects and show that our framework provides more flexibility and open up new opportunities for innovative development in the domain of microstructure recovery from diffusion MRI.

On the Viability of Diffusion MRI-Based Microstructural Biomarkers in Ischemic Stroke.

Recent tract-based analyses provided evidence for the exploitability of 3D-SHORE microstructural descriptors derived from diffusion MRI (dMRI) in revealing white matter (WM) plasticity. In this work, we focused on the main open issues left: (1) the comparative analysis with respect to classical tensor-derived indices, i.e., Fractional Anisotropy (FA) and Mean Diffusivity (MD); and (2) the ability to detect plasticity processes in gray matter (GM). Although signal modeling in GM is still largely unexplored, we investigated their sensibility to stroke-induced microstructural modifications occurring in the contralateral hemisphere. A more complete picture could provide hints for investigating the interplay of GM and WM modulations. Ten stroke patients and ten age/gender-matched healthy controls were enrolled in the study and underwent diffusion spectrum imaging (DSI). Acquisitions at three and two time points (tp) were performed on patients and controls, respectively. For all subjects and acquisitions, FA and MD were computed along with 3D-SHORE-based indices [Generalized Fractional Anisotropy (GFA), Propagator Anisotropy (PA), Return To the Axis Probability (RTAP), Return To the Plane Probability (RTPP), and Mean Square Displacement (MSD)]. Tract-based analysis involving the cortical, subcortical and transcallosal motor networks and region-based analysis in GM were successively performed, focusing on the contralateral hemisphere to the stroke. Reproducibility of all the indices on both WM and GM was quantitatively proved on controls. For tract-based, longitudinal group analyses revealed the highest significant differences across the subcortical and transcallosal networks for all the indices. The optimal regression model for predicting the clinical motor outcome at tp3 included GFA, PA, RTPP, and MSD in the subcortical network in combination with the main clinical information at baseline. Region-based analysis in the contralateral GM highlighted the ability of anisotropy indices in discriminating between groups mainly at tp1, while diffusivity indices appeared to be altered at tp2. 3D-SHORE indices proved to be suitable in probing plasticity in both WM and GM, further confirming their viability as a novel family of biomarkers in ischemic stroke in WM and revealing their potential exploitability in GM. Their combination with tensor-derived indices can provide more detailed insights of the different tissue modulations related to stroke pathology.

Ensemble average propagator-based detection of microstructural alterations after stroke.

PURPOSE: New analytical reconstruction techniques of diffusion weighted signal have been proposed. A previous work evidenced the exploitability of some indices derived from the simple harmonic oscillator-based reconstruction and estimation (3D-SHORE) model as numerical biomarkers of neural plasticity after stroke. Here, the analysis is extended to two additional indices: return to the plane/origin (RTPP/RTOP) probabilities. Moreover, several motor networks were introduced and the results were analyzed at different time scales. METHODS: Ten patients underwent three diffusion spectrum imaging (DSI) scans [1 week (tp1), 1 month (tp2) and 6 months (tp3) after stroke]. Ten matched controls underwent two DSI scans 1 month apart. 3D-SHORE was used for reconstructing the signal and the microstructural indices were derived. Tract-based analysis was performed along motor cortical, subcortical and transcallosal networks in the contralesional area. RESULTS: The optimal intra-class correlation coefficient (ICC) was obtained in the subcortical loop for propagator anisotropy (ICC [Formula: see text] 0.96), followed by generalized fractional anisotropy (ICC [Formula: see text] 0.94). The new indices reached the highest stability in the transcallosal network and performed well in the cortical and subcortical networks with the exception of RTOP in the cortical loop (ICC [Formula: see text] 0.59). They allowed discriminating patients from controls at the majority of the timescales. Finally, the regression model using indices calculated along the subcortical loop at tp1 resulted in the best prediction of clinical outcome. CONCLUSIONS: The whole set of microstructural indices provide measurements featuring high precision. The new indices allow discriminating patients from controls in all networks, except for RTPP in the cortical loop. Moreover, the 3D-SHORE indices in subcortical connections constitute a good regression model for predicting the clinical outcome at 6 months, supporting their suitability as numerical biomarkers for neuronal plasticity after stroke.

What lies beneath? Diffusion EAP-based study of brain tissue microstructure.

Diffusion weighted magnetic resonance signals convey information about tissue microstructure and cytoarchitecture. In the last years, many models have been proposed for recovering the diffusion signal and extracting information to constitute new families of numerical indices. Two main categories of reconstruction models can be identified in diffusion magnetic resonance imaging (DMRI): ensemble average propagator (EAP) models and compartmental models. From both, descriptors can be derived for elucidating the underlying microstructural architecture. While compartmental models indices directly quantify the fraction of different cell compartments in each voxel, EAP-derived indices are only a derivative measure and the effect of the different microstructural configurations on the indices is still unclear. In this paper, we analyze three EAP indices calculated using the 3D Simple Harmonic Oscillator based Reconstruction and Estimation (3D-SHORE) model and estimate their changes with respect to the principal microstructural configurations. We take advantage of the state of the art simulations to quantify the variations of the indices with the simulation parameters. Analysis of in-vivo data correlates the EAP indices with the microstructural parameters obtained from the Neurite Orientation Dispersion and Density Imaging (NODDI) model as a pseudo ground truth for brain data. Results show that the EAP derived indices convey information on the tissue microstructure and that their combined values directly reflect the configuration of the different compartments in each voxel.

Sparse Reconstruction Challenge for diffusion MRI: Validation on a physical phantom to determine which acquisition scheme and analysis method to use?

Diffusion magnetic resonance imaging (dMRI) is the modality of choice for investigating in-vivo white matter connectivity and neural tissue architecture of the brain. The diffusion-weighted signal in dMRI reflects the diffusivity of water molecules in brain tissue and can be utilized to produce image-based biomarkers for clinical research. Due to the constraints on scanning time, a limited number of measurements can be acquired within a clinically feasible scan time. In order to reconstruct the dMRI signal from a discrete set of measurements, a large number of algorithms have been proposed in recent years in conjunction with varying sampling schemes, i.e., with varying b-values and gradient directions. Thus, it is imperative to compare the performance of these reconstruction methods on a single data set to provide appropriate guidelines to neuroscientists on making an informed decision while designing their acquisition protocols. For this purpose, the SPArse Reconstruction Challenge (SPARC) was held along with the workshop on Computational Diffusion MRI (at MICCAI 2014) to validate the performance of multiple reconstruction methods using data acquired from a physical phantom. A total of 16 reconstruction algorithms (9 teams) participated in this community challenge. The goal was to reconstruct single b-value and/or multiple b-value data from a sparse set of measurements. In particular, the aim was to determine an appropriate acquisition protocol (in terms of the number of measurements, b-values) and the analysis method to use for a neuroimaging study. The challenge did not delve on the accuracy of these methods in estimating model specific measures such as fractional anisotropy (FA) or mean diffusivity, but on the accuracy of these methods to fit the data. This paper presents several quantitative results pertaining to each reconstruction algorithm. The conclusions in this paper provide a valuable guideline for choosing a suitable algorithm and the corresponding data-sampling scheme for clinical neuroscience applications.

From time series to biological network regulations: an evolutionary approach.

In this paper we present a new methodology, based on genetic algorithms and multiple linear regression, for discovering regulation mechanisms responsible for observed time series in biological networks. The modeling framework employed is called Metabolic P systems; they are deterministic and time-discrete dynamical systems proposed as an effective alternative to ordinary differential equations for modeling biochemical systems. Our methodology is here successfully applied to the mitotic oscillator in early amphibian embryos. Starting from the time series of substances involved in this system, we are able to reconstruct an MP system reproducing the observed dynamics, where the regulatory components were discovered by our evolutionary methodology. In particular, genetic algorithms are used as a variable selection technique to identify the best representation of any regulation function in terms of some given primitive functions.