COMMIT: Convex Optimization Modeling for Microstructure Informed Tractography

Tractography is a class of algorithms aiming at in vivo mapping the major neuronal pathways in the white matter from diffusion MRI data. These techniques offer a powerful tool to noninvasively investigate at the macroscopic scale the architecture of the neuronal connections of the brain. However, unfortunately, the reconstructions recovered with existing tractography algorithms are not really quantitative even though diffusion MRI is a quantitative modality by nature. As a matter of fact, several techniques have been proposed in recent years to estimate, at the voxel level, intrinsic microstructural features of the tissue, such as axonal density and diameter, by using multicompartment models. In this article, we present a novel framework to reestablish the link between tractography and tissue microstructure. Starting from an input set of candidate fiber-tracts, which are estimated from the data using standard fiber-tracking techniques, we model the diffusion MRI signal in each voxel of the image as a linear combination of the restricted and hindered contributions generated in every location of the brain by these candidate tracts. Then, we seek for the global weight of each of them, i.e. the effective contribution or volume, such that they globally fit the measured signal at best. We demonstrate that these weights can be easily recovered by solving a global convex optimization problem and using efficient algorithms. The effectiveness of our approach has been evaluated both on a realistic phantom with known ground-truth and in vivo brain data. Results clearly demonstrate the benefits of the proposed formulation, opening new perspectives for a more quantitative and biologically-plausible assessment of the structural connectivity of the brain.

Global tractography with embedded anatomical priors for quantitative connectivity analysis

Alessandro Daducci, Alia Lemkaddem, Didrik Hans Malcolm Skiöldebrand, Jean-Philippe Thiran

Tractography algorithms provide us with the ability to non-invasively reconstruct fiber pathways in the white matter (WM) by exploiting the directional information described with diffusion magnetic resonance. These methods could be divided into two major classes, local and global. Local methods reconstruct each fiber tract iteratively by considering only directional information at the voxel level and its neighborhood. Global methods, on the other hand, reconstruct all the fiber tracts of the whole brain simultaneously by solving a global energy minimization problem. The latter have shown improvements compared to previous techniques but these algorithms still suffer from an important shortcoming that is crucial in the context of brain connectivity analyses. As no anatomical priors are usually considered during the reconstruction process, the recovered fiber tracts are not guaranteed to connect cortical regions and, as a matter of fact, most of them stop prematurely in the WM; this violates important properties of neural connections, which are known to originate in the gray matter (GM) and develop in the WM. Hence, this shortcoming poses serious limitations for the use of these techniques for the assessment of the structural connectivity between brain regions and, de facto, it can potentially bias any subsequent analysis. Moreover, the estimated tracts are not quantitative, every fiber contributes with the same weight toward the predicted diffusion signal. In this work, we propose a novel approach for global tractography that is specifically designed for connectivity analysis applications which: (i) explicitly enforces anatomical priors of the tracts in the optimization and (ii) considers the effective contribution of each of them, i.e., volume, to the acquired diffusion magnetic resonance imaging (MRI) image. We evaluated our approach on both a realistic diffusion MRI phantom and in vivo data, and also compared its performance to existing tractography algorithms.

2014

Whole-brain structural connectivity in temporal lobe epilepsy: a Diffusion Spectrum Imaging study

Alessandro Daducci, Alessandra Griffa, François Lazeyras, Alia Lemkaddem, Jean-Philippe Thiran

Introduction: Medial Temporal Lobe Epilepsy (mTLE) with hippocampal sclerosis is the most frequent cause of drug-resistant focal epilepsy in adults. These patients suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor Imaging and functional MRI studies. Diffusion spectrum imaging (DSI) is a new diffusion imaging technique with high angular resolution for improving the mapping of white matter tracts [1]. In this study, we used DSI to investigate the whole brain effect of TLE as reflected by topological measures of the structural connectivity network. Methods: Eight patients with right-sided mTLE and hippocampal sclerosis and 25 controls underwent our DSI protocol at 3T using a 32 channel coil: DSI (voxel size 2.2x2.2x3mm; 44 slices, 257 diffusion directions; max b-value = 6400 s/mm2), 3D T1-weighted MPRAGE and 3D T2-weighted images. The analysis was performed using the Connectome Mapper. The cortical and subcortical grey matters were parcellated into 86 Regions of Interest (ROI) with anatomical landmarks using Freesurfer 5.0. The ROIs were coregistered to the diffusion data by using a nonlinear registration between T1 and T2, then T2 to the diffusion space. The Diffusion Tool Kit was used for the reconstruction of the diffusion Orientation Distribution Function in each voxel. Streamline fibre-tracking was then performed from each voxel in the white matter areas using an in-house streamline-based algorithm. Two scalar maps, the Fractional Anisotropy and the Generalized Fractional Anisotropy were calculated. For each patient, the connectivity between every region pair was estimated was used to construct a connectivity matrix (the adjacency matrix of the structural network). Finally we used topological measures in order to reduce the data and obtain whole-brain characteristics of the network [2]: characteristic Path Length (L), Clustering Coefficient (C) and Small Worldness (S) where S=(C/Crand)/(L/ Lrand) with Crand and Lrand are computed for a random network. Significant differences between the mTLE and control groups were assessed using a Wilcoxon rank-sum test. Results: In patients, we found a higher characteristic path length (0.0288), with a lower clustering coefficient (0.0079) and reduced small-worldness (p=0.000058) compared to controls. Network nodes that contributed significantly to these alterations were located within as well as outside the temporal lobe in both hemispheres, although with a predominance for the ipsilateral hemisphere and bilateral limbic structures. The pattern of significant nodes showed concordance with brain regions known to be involved in epileptic networks in patients with mTLE. Conclusions: Our results show a reduced efficiency of structural brain networks and altered connectivity patterns that are concordant with the mapping of functional epileptic networks [3] and altered functional connectivity [4] in patients with mTLE. Therefore, the network in mTLE is less segregated than in controls with reduced global interactions between the nodes and reduced specialised communities. Further studies are needed to establish the relevance of these findings with respect to the propagation of epileptic activity, cognitive deficits in mTLE and outcome of epilepsy surgery in individual patients.

2012

AxTract: Toward microstructure informed tractography

Alessandro Daducci, Maxime Descoteaux, Gabriel Girard, Jean-Philippe Thiran

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. (C) 2017 Wiley Periodicals, Inc.

Wiley-Blackwell2017