Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging

Focal epilepsy is increasingly recognized as the result of an altered brain network, both on the structural and functional levels and the characterization of these widespread brain alterations is crucial for our understanding of the clinical manifestation of seizure and cognitive deficits as well as for the management of candidates to epilepsy surgery. Tractography based on Diffusion Tensor Imaging allows non-invasive mapping of white matter tracts in vivo. Recently, diffusion spectrum imaging (DSI), based on an increased number of diffusion directions and intensities, has improved the sensitivity of tractography, notably with respect to the problem of fiber crossing and recent developments allow acquisition times compatible with clinical application. We used DSI and parcellation of the gray matter in regions of interest to build whole-brain connectivity matrices describing the mutual connections between cortical and subcortical regions in patients with focal epilepsy and healthy controls. In addition, the high angular and radial resolution of DSI allowed us to evaluate also some of the biophysical compartment models, to better understand the cause of the changes in diffusion anisotropy. Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

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

Brain network analysis of patients with Temporal Lobe Epilepsy

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

Patients with Temporal Lobe Epilepsy (TLE) suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor MR Imaging, volumetric and functional MRI studies. Diffusion Spectrum Imaging (DSI) is a diffusion imaging technique with high angular resolution for improving the mapping of white matter pathways. In this study, we used DSI, connectivity matrices and topological measures to investigate how the alteration in structural connectivity influences whole brain structural networks. Eleven patients with right-sided TLE and hippocampal sclerosis and 18 controls underwent our DSI protocol at 3T. The cortical and subcortical grey matters were parcellated into 86 regions of interest and the connectivity between every region pair was estimated using global tractography and a connectivity matrix (the adjacency matrix of the structural network). We then compared the networks of patients and controls using topological measures. In patients, we found a higher characteristic path length and a lower clustering coefficient compared to controls. Local measures at node level of the clustering and efficiency showed a significant difference after a multiple comparison correction (Bonferroni). These significant nodes were located within as well outside the temporal lobe, and the localisation of most of them was consistent with regions known to be part of epileptic networks in TLE. Our results show altered connectivity patterns that are concordant with the mapping of functional epileptic networks in patients with TLE. Further studies are needed to establish the relevance of these findings for the propagation of epileptic activity, cognitive deficits in medial TLE and outcome of epilepsy surgery in individual patients.

2013

Whole-brain structural connectivity in patients with focal epilepsy studied with MRI diffusion spectrum imaging (DSI)

Leila Cammoun, Tobias Kober, François Lazeyras, Alia Lemkaddem, Reto Meuli, Christoph Michel, Jean-Philippe Thiran

In patients with focal epilepsy, diffusion MRI often reveals structural changes extending beyond visible lesions or show structural abnormalities even when the clinical scans are normal. MR Tractography based on diffusion tensor imaging allows non-invasive mapping of white matter tracts in vivo. Recently, Diffusion Spectrum Imaging (DSI), based on an increased number of diffusion directions and intensities, has improved the sensitivity of tractography, notably with respect to the problem of fibre crossing and recent development allow acquisition times compatible with clinical application. We used DSI tractography and parcelation of the grey matter in regions of interest to build whole-brain connectivity matrices describing the mutual connections between cortical regions at different spatial resolutions in patients with focal epilepsy and healthy controls. The combination with other imaging modalities (EEG source imaging, PET, SPECT, EEG-fMRI) localising cortical regions corresponding to the irritative zone (IZ) or seizure onset zone (OZ) allows to reconstruct tracts of interest to map the connectivity of the IZ/OZ, as well as physiological close by tracts subserving normal neurological/cognitive functions. We here present our preliminary results on patients with lesional and cryptogenic epilepsy showing that this new analysis strategy allows investigating focal connectivity changes at a whole-brain level with unprecedented sensitivity. This opens new avenues for the understanding of epileptic networks and for clinical management of candidates for epilepsy surgery.