Patient-derived xenografts (PDXs) of human gliomas in murine models are unmatched in representing the molecular heterogeneity of the disease, but typically do not present with MRI contrast, and thus are not phenotypical. This may pose a limit to the assessment of trial therapies. PDX preparations were tweaked by co-injecting Matrigel with neurospheres. In one of the two cell lines studied, Matrigel promoted the formation of brain tumors whose genetic composition was that of the original human GBMs and whose radiologic appearance on MRI was similar to that seen in humans. In the second cell line, no BBB breakdown occurred.