Identification and interpretation of microstructural abnormalities in motor pathways in adolescents born preterm

There has been extensive interest in assessing the long-term effects of preterm birth on brain white matter microstructure using diffusion MRI. Our aim in this study is to explore diffusion MRI differences between adolescents born preterm and term born controls, with a specific interest in characterising how such differences are manifested in white matter regions containing predominantly single or crossing fibre populations. Probabilistic high angular resolution tractography together with large deformation spatial normalisation were used to objectively investigate diffusion tensor parameters at regular intervals along fibre tracts of 45 adolescents born before 33 weeks of gestation and 30 term-born typically developing adolescents. Diffusion parameters were significantly different between preterms and controls at several levels along the cortico-spinal, thalamo-cortical and transcallosal pathways. Within the predominantly single fibre regions of the corpus callosum and internal capsule, in the preterms mean diffusivity (MD) was found to be increased while fractional anisotropy (FA) was decreased compared to controls. In contrast, however, where these pathways traversed the centrum semiovale, FA and MD were both significantly increased. The major contributor to reduced FA in preterms in predominantly single fibre regions was the increased radial eigenvalue (i.e. increased radial diffusivity). In predominantly crossing-fibre regions, the tensor eigenvalues are not meaningful, and the observed increase in FA is likely to be due to a decrease in anisotropy in one of the contributing fibre bundles. Similar differences (although less pronounced) were observed after excluding preterms with radiological signs of preterm brain injury from the sample. In summary, white matter microstructure was found to be altered in motor pathways in adolescents born preterm. Disruption of white matter (WM) microstructure in a single fibre region with resulting higher radial diffusivity leads to lower FA, whereas selective disruption of one fibre population in a crossing fibre region is observed to lead to higher FA. These findings challenge the common simplistic interpretation of FA as a measure of WM tract integrity.