ABSTRACT: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), T 1 , T 2 , 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 T 1 , T 2 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, T 1 , T 2 , 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 T 2 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. I mprovements in neonatal medicine have been accompanied by an increase in the survival of small premature infants, with substantial numbers having adverse neurologic sequelae related to cerebral white matter injury (1-3). Although the pathogenesis may be uncertain, such brain injury can be a result of hypoxic-ischemic damage to the white matter consisting of focal cystic lesions deep in the periventricular white matter or a more diffuse noncystic white matter injury. Diagnosis of such white matter injury at an early acute stage is necessary for developing optimal clinical management and treatment strategies.Despite MRI techniques gaining acceptance for their evaluation of cerebral hypoxic-ischemic injury in neonates, information on the acute hypoxic-ischemic MRI changes and their evolution in immature white matter compared with gray matter remains limited (3-8). In general, MRI studies have shown that diffusion weighted imaging (DWI) is able to detect acute changes in the cerebral white matter of preterm infants where these changes are often not demonstrated on conventional MRI, i.e. T 1 or T 2 (5,9). In addition, more recent studies in term infants with hypoxic-ischemic encephalopathy show that the ADC of water is decreased in severely damaged white matter within the first week after birth and then tends to increase after the first week (7,8,10).Our recent study in neonatal rats has demonstrate...

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