A Framework for Detection and Observation of Radiation Chemistry Species on an MR-LINAC

Abstract

Radiation therapy, used in over half of cancer treatments, aims to target tumors while preserving healthy tissue. Existing techniques lack the ability to measure tissue damage during therapy, causing potential over- or under-irradiation, leading to severe side effects. Radiation inflicts DNA damage via direct and indirect mechanisms, the extents of each are inconsistent between patients, causing differences in response to radiation. Magnetic resonance-linear accelerators (MR-linacs) are promising to evaluate indirect DNA damage by measuring radiation chemistry species (RCS) produced during irradiation. In this work, MRI methods were developed to observe free radical production, radiation chemistry was modeled for select RCS scavengers and verified experimentally. These methods were then employed to measure MRI signal changes for complex combinations of RCS scavengers and radiosensitizing nanoparticles. Radiation chemistry experimental T1 changes were used to fit the relaxivity of the superoxide free radical and this value was assumed for all subsequent calculations. MRI T1 changes due to free radical production by radiation are presented in solutions consisting of water, 10 mM coumarin, 20 μM mito-TEMPO, 5 mM glutathione, a 20 μM mito-TEMPO and 5 mM glutathione mixture, 10 μM gold nanoparticles and 60 μM phosphate buffered saline. Radiation chemistry simulations completed for water and 10 mM coumarin show good agreement with their respective experimental T1 changes. Largest T1 changes and largest rates of production of superoxide were found in the 20 μM mito-TEMPO and 5 mM glutathione mixture, while smallest T1 changes and smallest rates of production of superoxide were found in the 20 μM mito-TEMPO solution. The main conclusions of this work show that a framework to detect T1 changes due to the production of free radical species during imaging and irradiation on a MR-linac has been developed, with the predominant source of T1 change over time due to free radicals attributed to the production of superoxide.