Influence of Dose Uniformity when Replicating a Gamma Knife Mouse Model of Radiation Necrosis with a Preclinical Irradiator.

A common mouse model used for studying radiation necrosis is generated with the gamma knife, which has a non-uniform dose distribution. The goal of this study was to determine whether the lesion growth observed in this mouse model is a function of non-uniform dose distribution and/or lesion progression. Here, a model similar to the gamma knife mouse model was generated; using a preclinical irradiator, mice received single-fraction doses from 50 to 100 Gy to a sub-hemispheric portion of the brain. The development of necrosis was tracked for up to 26 weeks with a 7T Bruker magnetic resonance imaging (MRI) scanner using T2 and post-contrast T1 imaging. MRI findings were validated with histology, specifically H&E staining. Single small beam 50 Gy irradiations failed to produce necrosis in a 26-week span, while doses from 60 to 100 Gy produced necrosis in a timeframe ranging from 16 weeks to 2 weeks, respectively. Postmortem histology confirmed pathological development in regions corresponding with those that showed abnormal signal on MRI. The growth of the necrotic lesion observed in this gamma knife model was due in part to a non-uniform dose distribution rather than to the increased severity of the lesion. Interpretation of results from the gamma knife model must take into consideration the potential effect of nonuniform dose distribution, particularly with regards to the timing of interventions. There are time points in this model at which pre-onset, onset and post-onset of radiation necrosis are all represented in the irradiated field.