Neural micro and macrostructural correlates of visual outcomes in children with unilateral cerebral palsy: A fixel-based study

Children with unilateral cerebral palsy (uCP) present with brain damage, predominantly lateralized to one hemisphere, and white matter (WM) lesions, which are known to affect visual functions. However, the relation between WM tract damage and visual outcomes remains unclear. Additionally, no prior study comprehensively investigated hemispheric-specific differences in WM visual pathways between children with left- and right-sided uCP. Therefore, this exploratory study aims to investigate differences in micro- and macrostructural properties of the visual pathways between children with left- and right-sided uCP and their relation to visual outcomes, using fixel-based analysis of diffusion MRI (dMRI). dMRI data and visual assessments, including visual acuity and stereoacuity (i.e., geniculostriate functions), motor-free visual perception, visuomotor integration, and functional vision, were analysed in 36 children with uCP (aged 7-15, 9 males, 17 left-sided, 15 preterm). Apparent fiber density (AFD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) were calculated for 17 WM tracts related to visual functions. Differences between children with left- and right-sided uCP were investigated using the Mann-Whitney <i>U</i>-test (<i>r</i>) on the AFD and one-way analysis of covariance (ANCOVA) (<i>η_p ²</i> ) on the FC and FDC, with age and intracranial volume as covariates. Correlations between visual outcomes and WM properties of the visual tracts were studied using (semi-partial) Spearman Rank correlations (<i>r_s</i> ). Children with left-sided uCP showed significantly lower fixel metrics in the right superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and optic radiation. Children with right-sided uCP had lower AFD, FC, and FDC in the left superior longitudinal fasciculus only. Reduced geniculostriate visual functions and more impairments in functional vision were associated with lower fiber density (AFD), reduction in bundle size (FC), and their combination (FDC) of several WM tracts. Lower performance on motor-free visual perception and visuomotor integration showed more associations with lower fiber density (AFD). While the primary analyses were exploratory and uncorrected for multiple comparison, false discovery rate (FDR) correction was additionally performed for transparency: several differences in FC and FDC between children with left- and right-sided uCP, and correlations between AFD and visual function, remained significant and are reported in the Supplementary Materials. In conclusion, our exploratory study highlights that fixel-based analysis can provide further insights into hemispheric differences in the visual system and the complex relations between visual functions and brain damage in children with uCP. Based on our results, future studies could refine regression models to target key WM tracts linked to visual outcomes, identifying potential biomarkers to predict visual impairments and enable early tailored support in children with uCP.