Ependymoma (EPN) is an aggressive pediatric brain tumor, for which the benefits of chemotherapy in pediatric patients have not been defined. EPN treated with surgery and radiation recur in 23-66% of patients. Our group has previously established aggressive behaviors of EPN, including high tumor cellularity, cytological anaplasia, high mitotic index, tumor necrosis, and the presence of inflammatory cells such as M2-type myeloid cells. Here we report on an advanced 9.4 Tesla MRI protocol for characterizing the cellular and vascular phenotype and treatment response to chemo-radiation therapy (CRT) in an orthotopic mouse model of patient derived xenografts (PDX) of pediatric EPN . Female severely immune deficient (SCID) mice were used for intracranial inoculation of disaggregated tumors from pediatric EPN patients (n=22). High-resolution T2w-MRI was able to detect cerebellar microlesions as small as 0.2 mm diameter; the median tumor volumes at the baseline were 21±12 mm3. Using diffusion-weighted based cell-size imaging, iron-oxide based vessel-size imaging and quantitative T2-maps, the EPN-specific phenotype was characterized by an increased cell size (S=14 microns), increased vessel density index (Q=0.54), and low ADC values (0.63x10-3). Once the intracranial tumors reached at least 5 mm3, animals were treated with CRT (10 Gy radiation plus 30 mg/kg 5-fluorouracil, n=6). CRT resulted in a tumor shrinkage, tumor necrosis with decreased cell sizes and increased ADC values, and a dramatic vascular-inflammatory response (decreased Q and DT2 values with the injection of iron oxide nanoparticles as macrophage-specific contrast). In summary, orthotopically implanted PDX EPN in mice closely mimic histological features, anatomical location and radiological features of the primary tumors. A significant decrease in vessel size density and an increase in inflammatory cells were seen as soon as 2 days after CRT. The late response (2 weeks post CRT) is characterized by decreased cellularity, cell size, and tumor volumes.