Microstructural changes of white matter assessed with diffusional kurtosis imaging in extremely preterm infants with severe intraventricular hemorrhage

Abstract

ObjectiveIntraventricular hemorrhage (IVH) is a serious neurological complication in premature infants. This study aimed to investigate the white matter impairments and neurodevelopmental outcomes of severe IVH in extremely preterm infants with gestation age less than 28 weeks.MethodsWe retrospectively evaluated the extremely preterm infants between 2017 and 2020. Neurodevelopmental outcomes were evaluated with the Bayley Scales of Infant and Toddler Development-III at 2 years of corrected age. Diffusional kurtosis imaging (DKI) was employed to evaluate the microstructural changes in white matter tracts. Mean kurtosis (MK) and fractional anisotropy (FA) values of DKI were measured in the brain regions including posterior limbs of the internal capsule (PLIC) and the corpus callosum at term equivalent age.ResultsOf 32 extremely preterm infants with severe IVH during the follow-up period, 18 cases were identified as neurodevelopmental impairments. The delay rates of motor and language were 58.4% and 52.7%. The cases with neurodevelopmental impairments had lower MK and FA values in both bilateral PLIC and the corpus callosum. The analysis of multivariable regression models predicting motor and language outcomes at 2 years of corrected age, showed that the decreases of MK values in both PLIC and the corpus callosum at the term equivalent age contributed to a significantly increased risk of neurodevelopmental impairments (all p < 0.05). During follow-up period, obvious loss of nerve fiber bundles was observed with DKI tractography.ConclusionMotor and language abilities at age 2 years were associated with MK values of DKI at the term equivalent age in both PLIC and the corpus callosum of extremely preterm infants with severe IVH. The evaluation of white matter microstructural changes with MK values might provide feasible indicators of neurodevelopmental outcomes of extremely preterm infants with severe intraventricular hemorrhage.

Associations between diffusion kurtosis imaging metrics and neurodevelopmental outcomes in neonates with low-grade germinal matrix and intraventricular hemorrhage

“…Our investigation identified significant deviations in MK within the thalamus and RK within the caudate nucleus, all of which emerged as pivotal factors associated with adverse outcomes in both MDI and PDI. This aligns seamlessly with existing literature that underscores the impact of low-grade GMH-IVH on macroscopic thalamus and caudate nucleus development, thereby contributing to compromised neurodevelopmental outcomes 12 , 26 , 27 . Supporting our findings, Han Y et al highlighted a correlation between neurodevelopmental outcomes and RK values in the caudate nucleus among neonates with encephalopathy 21 .…”

“…Additionally, RK evaluation may serve as a novel method for assessing the integrity of cell membranes and surrounding myelin sheaths 7 . Intriguingly, simultaneous decreases in MK and RK have been observed in other regions of brain injury resulting from axonal loss, followed by a decrease in the extracellular matrix and glial cells 12 , 24 , 25 . On the other hand, the lack of significant changes in FA values suggests that MK and RK metrics can reflect subtle differences, likely indicating milder microstructural alterations, such as minimal fiber loss without gross tissue damage 7 .…”

“…Its applications extend to various conditions, including prematurity 9 , spinal cord imaging 10 , and acute bilirubin encephalopathy 11 . Associations with neurodevelopmental outcomes have been explored, revealing adverse motor and language abilities in preterm infants with severe intraventricular hemorrhage 12 . Notably, these findings suggest a potential relationship between regional DKI-derived metrics and neurodevelopmental outcomes in preterm infants with severe intraventricular hemorrhage, yet few studies have specifically evaluated the correlation between DKI-derived metrics and neurodevelopmental outcomes in neonates with low-grade GMH-IVH.…”