MRI is a useful technology for longitudinal assessments, which are critical for understanding vascular changes in the brain. Exposure to high-altitude (HA), hypoxic conditions, e.g. by military personnel, can result in physiological changes and ultimately degradation of neurobehavioral performance. We utilized in vivo MR imaging in mice to examine changes in brain vasculature, myelination and structure and to provide longitudinal insights into pathological changes caused by long-term exposure to HA. We observed changes in T2 that reflect edema/inflammation, fractional anisotropy changes that suggest changes in white matter myelination, and rCBF and VDi imaging indicating adaptations to HA conditions.