At present it is not possible to reliably identify patients that will benefit from oncolytic virus treatments. Conventional modalities such as computed tomography (CT), which measure tumor size, are unreliable due to inflammation-induced tumor swelling. We hypothesized that magnetic resonance imaging (MRI) and spectroscopy (MRS) might be useful in this regard. However, little previous data exists and neither oncolytic adenovirus nor immunocompetent models have been assessed by MRS. Here we provide evidence that in T2 weighted MRI a hypointense core area, consistent with coagulative necrosis, develops in immunocompetent Syrian hamsters carcinomas that respond to oncolytic adenovirus treatment. The same phenomenon was observed in a neuroblastoma patient while he responded to the treatment. With relapse at a later stage, however, the tumor of this patient became moderately hyperintense. We found that MRS of taurine, choline and unsaturated fatty acids can be useful early indicators of response and provide detailed information about tumor growth and degeneration. In hamsters, calprotectin positive inflammatory cells (heterophils, macrophages) were found in abundance particularly surrounding necrotic areas in carcinomas and T cells were significantly increased in sarcomas, when these had been treated with a GM-CSF producing virus, suggesting a possible link between oncolysis, necrosis (seen as a hypointense core in MRI) and/or immune response. Our study indicates that both MRI and MRS could be useful in the estimation of oncolytic adenovirus efficacy at early timepoints after treatment. © 2013 Wiley Periodicals, Inc.