Automated tractography in patients with temporal lobe epilepsy using TRActs Constrained by UnderLying Anatomy (TRACULA)

Barbara A.K Kreilkamp,Bernd Weber,Mark P Richardson,Simon S Keller

doi:10.1016/j.nicl.2017.01.003

Abstract

PurposeA detailed understanding of white matter tract alterations in patients with temporal lobe epilepsy (TLE) is important as it may provide useful information for likely side of seizure onset, cognitive impairment and postoperative prognosis. However, most diffusion-tensor imaging (DTI) studies have relied on manual reconstruction of tract bundles, despite the recent development of automated techniques. In the present study, we used an automated white matter tractography analysis approach to quantify temporal lobe white matter tract alterations in TLE and determine the relationships between tract alterations, the extent of hippocampal atrophy and the chronicity and severity of the disorder.MethodsWe acquired preoperative T1-weighted and DTI data in 64 patients with well-characterized TLE, with imaging and histopathological evidence of hippocampal sclerosis. Identical acquisitions were collected for 44 age- and sex-matched healthy controls. We employed automatic probabilistic tractography DTI analysis using TRActs Constrained by UnderLying Anatomy (TRACULA) available in context of Freesurfer software for the reconstruction of major temporal lobe tract bundles. We determined the factors influencing probabilistic tract reconstruction and investigated alterations of DTI scalar metrics along white matter tracts with respect to hippocampal volume, which was automatically estimated using Freesurfer's morphometric pipelines. We also explored the relationships between white matter tract alterations and duration of epilepsy, age of onset of epilepsy and seizure burden (defined as a function of seizure frequency and duration of epilepsy).ResultsWhole-tract diffusion characteristics of patients with TLE differed according to side of epilepsy and were significantly different between patients and controls. Waypoint comparisons along each tract revealed that patients had significantly altered tissue characteristics of the ipsilateral inferior-longitudinal, uncinate fasciculus, superior longitudinal fasciculus and cingulum relative to controls. Changes were more widespread (ipsilaterally and contralaterally) in patients with left TLE while patients with right TLE showed changes that remained spatially confined in ipsilateral tract regions. We found no relationship between DTI alterations and volume of the epileptogenic hippocampus. DTI alterations of anterior ipsilateral uncinate and inferior-longitudinal fasciculus correlated with duration of epilepsy (over and above effects of age) and age at onset of epilepsy. Seizure burden correlated with tissue characteristics of the uncinate fasciculus.ConclusionThis study shows that TRACULA permits the detection of alterations of DTI tract scalar metrics in patients with TLE. It also provides the opportunity to explore relationships with structural volume measurements and clinical variables along white matter tracts. Our data suggests that the anterior temporal lobe portions of the uncinate and inferior-longitudinal fasciculus may be particularly vulnerable to pathological alterations in patients with TLE. These alterations are unrelated to the extent of hippocampal atrophy (and therefore potentially mediated by independent mechanisms) but influenced by chronicity and severity of the disorder.

Highlights

IntroductionExtrahippocampal abnormalities have been frequently described in temporal lobe epilepsy (TLE), including cortical and subcortical gray matter alterations demonstrated using morphometric techniques (see reviews by Bernhardt et al, 2013; Keller and Roberts, 2008; Richardson, 2012; Bonilha and Keller, 2015) and white matter tract alterations using diffusion tensor imaging (DTI) and tractography (see reviews by Rodríguez-Cruces and Concha, 2015; Gross, 2011)
We investigated the relationships between extent of hippocampal atrophy, as quantified using Freesurfer morphometric tools, temporal lobe white matter tract alterations, and various clinical aspects of temporal lobe epilepsy (TLE)
We found that whole-tract fractional anisotropy (FA)/mean diffusivity (MD) abnormalities were observed in most temporal lobe tracts investigated, the effects being observed bilaterally, but most strongly ipsilaterally

Summary

Introduction

Extrahippocampal abnormalities have been frequently described in TLE, including cortical and subcortical gray matter alterations demonstrated using morphometric techniques (see reviews by Bernhardt et al, 2013; Keller and Roberts, 2008; Richardson, 2012; Bonilha and Keller, 2015) and white matter tract alterations using diffusion tensor imaging (DTI) and tractography (see reviews by Rodríguez-Cruces and Concha, 2015; Gross, 2011). The recent revision of seizure disorder definitions to acknowledge the importance of networks for the onset of focal seizures (Berg and Scheffer, 2011) has encouraged a new direction of imaging research to model neuroimaging data in context of structural and functional networks and connectivity (Richardson, 2012). Reconstruction of white matter tracts from DTI data represent the most frequently applied technique of generating structural connectivity in the human brain (Jellison et al, 2004; Mori et al, 2009)

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