Exploring white matter abnormalities in different subtypes of spastic cerebral palsy using fixel-based analysis

Purpose To examine the white matter integrity in participants with cerebral palsy (CP) and among its different subtypes through diffusion MRI. Methods 34 participants with CP (19 boys, 15 girls; mean age: 13.9 ± 3.6 years) and 27 typically developing (TD) participants (14 boys, 13 girls; mean age: 14.5 ± 3.2 years) were enrolled. Diffusion-weighted and T2-weighted images were obtained. Clinical assessments included Gross Motor Function Classification System, Manual Ability Classification System, and Bimanual Fine Motor Function test. Diffusion-weighted images were analyzed by fixel-based analysis and Tract-based spatial statistics. Lesion map was calculated from the T2-weighted images. Differences in fixel-based metrics between CP or its subtype to TD participants, and among different subtypes, were evaluated through connectivity-based fixel enhancement and non-parametric permutation testing. The association of fixel-based metrics with clinical assessment scores was examined through general linear model. Results White matter damage can be noticed in CP participants, including corpus callosum, corticospinal tract, thalamic radiation, and optic radiation, when compared to TD participants. Fixel-based analysis detected additional regions in genu of corpus callosum. Fixel-based metrics in thalamic radiation and corticospinal tract were related to the severity of the motor impairment. Participants with diplegia had damage in the body of the corpus callosum and optic radiation when compared to those with hemiplegia. Conclusion Fixel-based analysis is sensitive to identify subtle white matter alterations that vary by CP subtype. The microstructural and macrostructural integrity of the corticospinal tract and thalamic radiation could be considered as promising image-based biomarkers to enhance clinical assessment.