Purpose: Using magnetic resonance (MR) and isotopic imaging to investigate the cerebral alterations after high-dose single-fraction irradiation on a pig model. We assessed the nuclear magnetic resonance (NMR) relaxation times as early markers of radiation injury to the healthy brain.Methods and Materials: A total of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T 1 -weighted scans, T 2 -weighted scans, and scintigrams were performed on all animals to study neurological abnormalities, cerebral blood flow, and blood-brain barrier (BBB) integrity. T 1 and T 2 relaxation times were measured in selected regions of interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T 1 after irradiation/T 1 before irradiation, and a ratio T 2 after irradiation/T 2 before irradiation, were calculated, pooled for each dose group, and followed as a function of time after irradiation.Results: Scintigraphy visualized the brain perfusion defect and BBB disruption in all irradiated brains. The ratio T 2 after irradiation/T 2 before irradiation was proportional to the effective dose received. The T 2 ratio kinetics could be analyzed in three phases: an immediate and transient phase, two long-lasting phases, which preceded compression of the irradiated lateral ventricle, and edema and necrosis at later stages of radiation injury, respectively. The magnetic resonance imaging (MRI) observations correlated well with histological analysis.Conclusion: The results show that quantitative imaging is a sensitive in vivo method for early detection of cerebral radiation injury. The reliability and dose dependence of T 2 relaxation time may offer new opportunities to detect and understand brain pathophysiology after high-dose single-fraction irradiation.