009. Microstructural periventricular white matter injury in post-hemorrhagic hydrocephalus

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Authors: Albert M Isaacs, MD PhD

The neurological deficits of post-hemorrhagic hydrocephalus (PHH) have been linked to periventricular white matter injury. To improve understanding of PHH-related injury, diffusion basis spectrum imaging (DBSI) was applied in neonates, modeling white matter pathologies, associating with ventricular size, and examining MRI findings in the context of post-mortem white matter histology.Methods: A prospective cohort of 95 preterm infants underwent term equivalent MRI, including infants with PHH, high-grade intraventricular hemorrhage without hydrocephalus (IVH), and controls (VPT). DBSI metrics extracted from the corpus callosum, corticospinal tracts, and optic radiations included fiber axial and radial diffusivities, fiber fractional anisotropy, fiber density, cellular infiltration, and vasogenic edema. Measures were compared across groups and correlated with ventricular size. Corpus callosum postmortem immunohistochemistry in PHH and control infants assessed intra/extra-fiber pathologies.
Overall, 68 VPT, 15 IVH, 12 PHH infants were assessed. PHH had the most severe white matter abnormalities, with no consistent differences between IVH and VPT groups. Key tract-specific white matter injury patterns in PHH included reduced fiber density in the setting of axonal and/or myelin injury, increased cellular infiltration, vasogenic edema, and inflammation. Axonal injury was highest in the corpus callosum; both axonal and myelin injury were observed in the corticospinal tracts; and axonal and myelin integrity were preserved in the setting of increased cellular infiltration and edema in the optic radiations. Increasing ventricular size correlated with worse DBSI metrics. On histology, PHH infants had high cellularity, variable cytoplasmic vacuolation, and low synaptophysin marker intensity.
PHH was associated with diffuse white matter injury, including tract-specific patterns of axonal and myelin injury, fiber loss, cellular infiltration, and inflammation. Larger ventricular size was associated with greater disruption. Postmortem immunohistochemistry confirmed MRI findings. These results demonstrate DBSI provides an innovative approach for investigating neuropathological effects of PHH on neonatal brain development.