Structural brain connectivity in children after neonatal stroke: A whole-brain fixel-based analysis

INTRODUCTION: Neonatal arterial ischemic stroke (NAIS) has been shown to affect white matter (WM) microstructure beyond the lesion. Here, we employed fixel-based analysis, a technique which allows to model and interpret WM alterations in complex arrangements such as crossing fibers, to further characterize the long-term effects of NAIS on the entire WM outside the primary infarct area. MATERIALS AND METHODS: 32 children (mean age 7.3 years (SD 0.4), 19 male) with middle cerebral artery NAIS (18 left hemisphere, 14 right hemisphere) and 31 healthy controls (mean age 7.7 years (SD 0.6), 16 male) underwent diffusion MRI scans and clinical examination for manual dexterity. Microstructural and macrostructural properties of the WM were investigated in a fixel-based whole-brain analysis, which allows to detect fiber-specific effects. Additionally, tract-averaged fixel metrics in interhemispheric tracts, and their correlation with manual dexterity, were examined. RESULTS: Significantly reduced microstructural properties were identified, located within the parietal and temporal WM of the affected hemisphere, as well as within their interhemispheric connecting tracts. Tract-averaged fixel metrics showed moderate, significant correlation with manual dexterity of the affected hand. No increased fixel metrics or contralesional alterations were observed. DISCUSSION: Our results show that NAIS leads to long-term alterations in WM microstructure distant from the lesion site, both within the parietal and temporal lobes as well as in their interhemispheric connections. The functional significance of these findings is demonstrated by the correlations with manual dexterity. The localization of alterations in structures highly connected to the lesioned areas shift our perception of NAIS from a focal towards a developmental network injury.