Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography ☆ Serena J. Counsell, a, ⁎ Leigh E. Dyet, b David J. Larkman, a Rita G. Nunes, a James P. Boardman, a,b Joanna M. Allsop, a Julie Fitzpatrick, a Latha Srinivasan, a,b Frances M. Cowan, b Joseph V. Hajnal, a Mary A. Rutherford, a,b and A. David Edwards a,b a Robert Steiner MR Unit, Imaging Sciences Department, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, DuCane Road, London, W12 0HS, UK b Department of Paediatrics, Imaging Sciences Department, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, DuCane Road, London, W12 0HS, UK Received 10 July 2006; revised 25 September 2006; accepted 29 September 2006 Available online 15 December 2006 Our aim was to investigate the feasibility of studying white matter tracts and connections between the thalamus and the cortex in 2-year- old infants who were born preterm by probabilistic magnetic resonance (MR) tractography. Using this approach, we were able to visualize and quantify connectivity distributions in a number of white matter tracts, including the corticospinal tracts, optic radiations, fibers of the genu and splenium of the corpus callosum, superior longitudinal fasciculus and inferior fronto-occipital fasciculus, and to map the distribution within thalamus of fibers connecting to specific cortical regions. In eleven infants with no MR evidence of focal cerebral lesions and appropriate neurodevelopment as shown by general quotient (GQ) scores above 100, we mapped cortical connections to the thalamus that appeared similar to those reported in adults. However, in a proof-of- principle experiment, we examined one further child with marked white matter abnormalities and found that the volume and pattern of thalamo-cortical connections were severely disrupted. This technique promises to be a useful tool for assessing connectivity in the developing brain and in infants with lesions. © 2006 Elsevier Inc. All rights reserved. Introduction The incidence of preterm birth is increasing (Langhoff-Roos et al., 2006) and now accounts for 13% of all births in the UK (< 37 weeks gestation) (Perinatal Survey Office, 1999). Survivors of preterm birth have a high incidence of cognitive impairment and behavioral problems compared to infants who were born at term (Bhutta et al., 2002; Marlow et al., 2005). Quantitative magnetic resonance imaging (MRI) studies have demonstrated abnormalities in the size and/or rate of growth in most brain regions studied in the preterm brain (Ajayi-Obe et al., 2000; Counsell et al., 2003, 2006; Huppi et al., 1998; Inder et al., 1999, 2005; Kapellou et al., 2006; Neil et al., 1998). Some studies have suggested that development of structures such as cerebellum, thalamus and basal ganglia is particularly impaired in the presence of white matter injury (Boardman et al., 2006; Srinivasan et al., 2006), suggesting that at least part of the reason for reduced growth may be disrupted neural connectivity in preterm infants. There is, therefore, a compelling need for reproducible and objective techniques which are able to assess connectivity directly in these infants. Diffusion tensor imaging (DTI) tractography provides a poten- tially valuable tool to assess connectivity in vivo. Prior to DTI tractography, information regarding brain connectivity was derived from dissection of the brain (Talairach and Tournoux, 1988) and histology of main fiber tracts (Burgel et al., 1997, 1999). However, in coherently organized cerebral white matter, water molecules preferentially diffuse along the direction of a white matter tract (Moseley et al., 1990). In DTI tractography, it is assumed that the eigenvector associated with the largest eigenvalue is aligned with the direction of the fiber bundle. By determining the direction of preferred direction of diffusion, it is possible to delineate white matter tracts in the brain. A number of studies have assessed white matter connectivity in infants and children using DTI tractography. These studies have investigated changes associated with normal maturation (Berman et al., 2005; Dubois et al., 2006; Partridge et al., 2005; Yoo et al., 2005) and pathology (Hoon et al., 2002; Partridge et al., 2006; Seghier et al., 2005; Thomas et al., 2005), but have not been able to map the detailed connections of important structures such as the thalamus, largely because of the technical difficulty of delineating tracts in areas of low anisotropy. Recently, a probabilistic technique which overcomes this problem has allowed definition of the tracts connecting cortex and thalamus and the in vivo description of the www.elsevier.com/locate/ynimg NeuroImage 34 (2007) 896 – 904 ☆ This work was presented at the annual general meeting of the International Society for Magnetic Resonance in Medicine, Seattle, WA, USA, 2006. ⁎ Corresponding author. E-mail address: serena.counsell@imperial.ac.uk (S.J. Counsell). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2006.09.036