Altered brain growth dynamics causing excessive white matter (WM) connections in some portions of the brain and underconnectivity in others, is a recently proposed etiological model for autism spectrum disorders (Courchesne et al, 2007). WM maturation and WM connectivity can be studied with diffusion tensor imaging (DTI), which allows reconstruction of WM fiber tracts (fiber tractography, FT). However, FT results highly depend on the manual delineation of regions-of-interest (ROI) and the algorithm settings, often rendering the reproducibility and reliability questionable. Predefining these ROI on a fractional anisotropy (FA) atlas in standard space has already been shown to improve the reliability of FTresults (Wakana et al, 2008).
When studying neurodevelopmental diseases, the availability of reliable data processing techniques and normative data from healthy controls is essential for the interpretation of pathological findings.
The aim of our study was to obtain normative DTI data by studying laterality and age-related maturational WM changes in 42 normal subjects aged 0 to 18 years using tractography-derived tract segmentations in a standard DTI atlas space.
DTI data were acquired at 3T using a SE-EPI sequence with 45 directions of diffusion (b = 800 s/mm2). First, a DTI atlas containing full diffusion information was generated using DTI data of 36 healthy volunteers (age range = 19-24 years) and both affine and non-rigid coregistration of the DTI data (Van Hecke et al, 2007). On the resulting DTI atlas, we performed deterministic FT of 11 bilateral and 4 unilateral WM tracts using robust ROI definition protocols (Wakana et al, 2008; Stieltjes et al,2003). Tract masks were derived from the tract reconstructions and were used to extract mean FA- and MD-values for each tract in 42 individual DTI datasets of children aged 4 months-18 years. WM maturation was assessed by evaluating the effect of age on FA or mean diffusivity (MD) using Pearson correlation tests. WM asymmetry was evaluated by performing paired t-tests on the left and right mean FA- or MD-values obtained in the bilateral WM tracts after correction for age. Statistical threshold for significance was set at p<0.05 and Bonferroni correction was applied to account for multiple testing.
Significant increase of FA and decrease of MD with age was found in all of the 26 tract masks. The decrease of FA was shown to be mainly due to the decrease of perpendicular diffusivity with age. In 6 out of 11 bilateral tracts, significant asymmetry of FA and MD was demonstrated.
We have generated a DTI atlas containing the full diffusion information in standard coordinate space, from which tract masks can be derived. Using these tract masks, we observed maturational changes in most of the major WM tracts in healthy children, providing normative data for the study of neurodevelopmental disorders. Furthermore, major functional pathways in the language, motor, and limbic system, showed significant asymmetry in terms of the observed diffusion metrics. Tract masks may thus be helpful in delineating how typical developmental trajectories are altered in individuals with developmental disorders, such as autism spectrum disorders.