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Background: Diffusion MR techniques are increasingly utilized in human preterm infants to reflect white matter microstructure and its integrity.Objective: To assess the relationship of the apparent diffusion coefficient (ADC), from diffusion MR imaging, to the severity of white matter injury and maturation in fixed tissue from a baboon model of premature birthMethods: Thirty-one baboons were delivered at 125 d gestational age (GA, equivalent to 28 weeks GA in the human) and were sacrificed between 139 and 160 d post-conceptional age (PCA). Support included surfactant, ventilator support, inotropic support, TPN, and physiological monitoring. Following sacrifice, the brains were immersion fixed in 10% formalin. Control data were obtained from 9 animals sacrificed immediately after delivery, from 90 to 160 d. MR data were obtained using a 4.7-T system and DTIs generated using a 2D spin echo pulse sequence. ADC values were analyzed as pairs in the frontal, central, and occipital areas. Forebrain sections were stained with H,E and glial fibrillary acidic protein to assess cerebral injury and gliosis. A white matter abnormality score (WMAS) was formulated using the presence of ventriculomegaly, areas of axonal damage, white matter gliosis and GFAP immunoreactivity in radial glial fibers. Damage was scored throughout the rostral-caudal extent of the brain; scale 0 (no abnormality) to 22 (severe abnormality).Results: On linear regression there was a direct relationship between the mean ADC and the PCA within the gestational control group (b=-0.001, p=0.01). There was also a direct relationship between ADC and WMAS for each region, which persisted when adjusted for PCA (b= 0.03, p < 0.01 central region).Conclusions: The association of white matter gliosis and axonal damage with elevated ADC values supports the hypothesis that elevated ADC values, as described in premature infants, reflect white matter injury with associated alterations in white matter microstructure.