Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography Michel Thiebaut de Schotten a,b,c, ⁎, Dominic H. ffytche a,b , Alberto Bizzi d , Flavio Dell'Acqua a,b,g , Matthew Allin e , Muriel Walshe e,f , Robin Murray f , Steven C. Williams b , Declan G.M. Murphy a , Marco Catani a,b a Natbrainlab, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College London, London, UK b Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK c CENIR—Centre de Neuroimagerie de Recherche, Hôpital de la Salpêtrière, 75651 Paris, France d Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Milan, Italy e Department of Psychiatry, Institute of Psychiatry, King's College London, London, UK f Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK g NIHR Specialist Biomedical Research Center for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, London, UK abstract article info Article history: Received 3 April 2010 Revised 18 June 2010 Accepted 25 July 2010 Available online 2 August 2010 Keywords: Diffusion tensor imaging Tractography White matter connections Atlas Brain asymmetries Inter-subject variability The purpose of this study is to create a white matter atlas of the human brain using diffusion tensor imaging (DTI) tractography and to describe the constant and variable features of the major pathways. DTI was acquired from 40 healthy right-handed adults and reconstructed tracts mapped within a common reference space (MNI). Group effect maps of each tract defined constant anatomical features while overlap maps were generated to study inter-subject variability and to compare DTI derived anatomy with a histological atlas. Two patients were studied to assess the localizing validity of the atlas. The DTI-derived maps are overall consistent with a previously published histological atlas. A statistically significant leftward asymmetry was found for the volume and number of streamlines of the cortico-spinal tract and the direct connections between Broca's and Wernicke's territories (long segment). A statistically significant rightward asymmetry was found for the inferior fronto-occipital fasciculus and the fronto-parietal connections (anterior segment) of the arcuate fasciculus. Furthermore, males showed a left lateralization of the fronto-temporal segment of the arcuate fasciculus (long segment), while females had a more bilateral distribution. In two patients with brain lesions, DTI was acquired and tractography used to show that the tracts affected by the lesions were correctly identified by the atlas. This study suggests that DTI-derived maps can be used together with a previous histological atlas to establish the relationship of focal lesions with nearby tracts and improve clinico-anatomical correlation. © 2010 Elsevier Inc. All rights reserved. Introduction Until the advent of diffusion tensor imaging (DTI), our knowledge of white matter anatomy was based on a small number of influential 19th and early 20th century post-mortem dissection atlases (Burdach, 1819; Déjerine, 1895). In common with their contemporary counterparts (Talairach and Tournoux, 1988), these atlases emphasize the constant or average anatomy of representative subjects at the expense of normal variability between subjects. Few post-mortem histological studies addressed the variability of the tracts between the two hemispheres and reported asymmetries for the cortico-spinal tract (CST) (Flechsig, 1876; Yakovlev and Rakic, 1966; Rademacher et al., 2001), the optic radiations (Bürgel et al., 1999), and the uncinate (Highley et al., 2002). Bürgel et al. (2006) showed that a significant inter-subject variability also exists for each tract within the single hemispheres. Little is known about whether such anatomical variability differs between genders and extends to other tracts underlying complex cognitive functions. Diffusion tensor imaging has allowed the study of the in vivo anatomy of white matter tracts in the human brain (Catani et al., 2002; Mori et al., 2002, 2005; Wakana et al., 2004; Catani and Thiebaut de Schotten, 2008; Ciccarelli et al., 2008; Lawes et al., 2008) and addressed some of the questions that were difficult to answer with post-mortem dissections such as the location, asymmetry and inter-subject variability of white matter tracts (Ciccarelli et al., 2003; Barrick et al., 2007; Catani et al., 2007; Wakana et al., 2007; Verhoeven et al., 2010). In the recent years several groups have used DTI to produce group atlases of the major white matter tracts (Hua et al., 2008; Lawes et al., 2008; Verhoeven et al., 2010; Wassermann et al., 2010). These atlases contain maps of the major white matter tracts that have a good correspondence with post-mortem blunt NeuroImage 54 (2011) 49–59 ⁎ Corresponding author. Natbrainlab, Department of Forensic and Neurodevelop- mental Sciences, Institute of Psychiatry, 16 De Crespigny Park, SE5 8AF London UK. E-mail address: michel.thiebaut@gmail.com (M. Thiebaut de Schotten). 1053-8119/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2010.07.055 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg