Background: The brain energy metabolism of severely birth asphyxiated human neonates, measured by 31P-Magnetic Resonance Spectroscopy(31P-MRS), shows a secondary energy failure (SEF) 2-4 days after hypoxic-ischemic (HI) insult. The prognostic value of neonatal 31P-MRS, given by trough values of energy metabolites, critically depends on the correct time point and placement of measurement within the brain. Quantitative maps of the apparent diffusion coefficient (ADC) are faster to obtain on routine MR Systems compared to 31P-MRS and provide spatially higher resolved information about the postischemic brain. Aim: To test if ADC maps, obtainable early after HI, are a reliable and predictive parameter of post HI brain outcome in rats. Methods: Right sided HI brain damage was produced in two groups of 7d rats (unilateral carotid artery ligation and exposure to 8% 02 for 1.5h). Group 1 (n = 8) was kept normothermic (37 °C) and group 2(n = 8) hypothermic (30 °C) for 24h after HI. 31P-MRS, DWI and T2-WI were acquired and quantitative ADC maps were processed continuously up to 4 days .Results and Discussion: The evolution of Pcr/Pi revealed partial recovery within 10h after HI, followed by a SEF at 24h, which was profound in normothermic but mild in hypothermic animals. The final extent of brain damage was correctly predicted by the ratio Pcr/Pi. During HI both groups showed declined ADC in the affected region (primary cytotoxic edema), which normalized within 2h after HI. After a second decline, trough ADC was measured between 10h and 25h post HI. At 15h 80% and at 24h of the maximal extent of the cytotoxic edema was visible. The ADC values were comparable in the core region in both groups, whereas they were 20% higher in the penumbra of hypothermic animals. The maximal edema occupied 45% of the brain in normothermic and 22% in the hypothermic group. Finally, the ADC increased in the core regions saturating at values of free water at 4 to 6 days. The sizes of the final infarcts were 35% in the normothermic compared to 15% in the hypothermic group. Conclusions: 1. In all animals primary cytotoxic edema marked brain area at risk. 2. The spatial distribution of trough values of ADC at 15h became necrotic after 4 to 6 d. 3. At equal primary lesions, the size of the final infarcts were 50% smaller in hypothermic compared to normothermic animals. 4. The ADC maps predicted the final infarct size 10 to 15h earlier, could be detected longer and permitted higher spatial resolution compared to 31P-MRS.