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We hypothesized that a combination of quantitative magnetic resonance imaging (MRI) sequences would detect a differential evolution of hypoxic-ischemic changes in white matter compared with gray matter in a recently developed model of unilateral mild cerebral hypoxia-ischemia in the 7-d-old rat. Using this model, which involved unilateral carotid artery occlusion and exposure to hypoxia for 45-50 min, maps of apparent diffusion coefficients of water (ADC), T1, T2, and cerebral blood flow (CBF) were acquired either before hypoxia-ischemia or at 1, 24, or 48 h and at 7 d post-hypoxia-ischemia followed by brain processing for histology. At 1 h post-hypoxia-ischemia, MRI changes in white matter ipsilateral to the hypoxia-ischemia were not as pronounced as those in gray matter. However, increases in T1, T2 and ADC and decreases in CBF within white matter enhanced over time, with changes being maximal at 48 h post-hypoxia-ischemia, whereas changes in the cortical gray matter normalized over this time. By 7 d post-hypoxia-ischemia, there were no differences in ADC, T1, T2, or CBF between hemispheres despite there being histologic changes in white matter within the hypoxic-ischemic hemisphere including increased glial proliferation and reactivity, reduced myelin basic protein, and increased cell death. The results demonstrate that increases in ADC and T2 observed subacutely in the days following hypoxia-ischemia are associated with rather selective white matter damage and suggest that diffuse white matter hyperintensities and increased ADC reported in infants are transient MRI changes post- hypoxia-ischemia.

pediatric research

Evolution of Magnetic Resonance Imaging Changes Associated with Cerebral Hypoxia-Ischemia and a Relatively Selective White Matter Injury in Neonatal Rats