Multimodal MRI of white matter development and selective motor control in preterm infants

• Corticospinal tract myelination closely tracks the emergence of selective motor control in very preterm infants. • Myelin-sensitive MRI (macromolecular proton fraction) provides a stronger structure–function link than diffusion metrics alone. • Early deviations in corticospinal and rubrospinal myelination identify atypical motor pathway development relevant to cerebral palsy. Selective motor control (SMC), the capacity to isolate joint movements, emerges in infancy and is a hallmark of typical development (TD). In infants with cerebral palsy (CP), SMC predicts future motor abilities. Although SMC is thought to reflect increasing cortical influence, its neural substrates remain poorly characterized. This study employed multimodal MRI to investigate the relationship between corticospinal tract (CST) microstructure and SMC in very preterm infants at high risk of CP. 15 very preterm infants, born before 32 weeks’ gestation with birthweight < 1500 g, underwent one or two MRI exams (total 20) between 3- and 21-week corrected age. Imaging included macromolecular proton fraction (MPF) mapping to quantify myelin, diffusion tensor imaging (DTI) to assess fractional anisotropy (FA), and g-ratio estimation. SMC was evaluated at the time of MRI. Regions of interest included the posterior limb of the internal capsule (PLIC), rubrospinal tract, and corpus callosum. Of the 15 infants studied, at the Bayley-4 assessment at 2 years, one was later diagnosed with spastic CP, one infant exhibited early motor delay but walked independently by age 2, and the remaining 13 had typical motor development. In infants with typical development, SMC scores increased with age and correlated with MPF in the PLIC (R 2 = 0.81). The rate of MPF increase in the CST outpaced that of the corpus callosum, 3.58% vs. 1.11% per week. In the infant with CP, a left hemisphere injury was associated with reduced MPF in the left CST and lower contralateral SMC, whereas rubrospinal MPF was elevated on the ipsilesional side. Early CST myelination parallels the emergence of SMC. Quantitative myelin imaging, particularly MPF, may serve as a sensitive structural biomarker of motor system maturation and emerging motor control, enabling early detection and intervention in CP.