MRI Radiomic Features of Radiation Induced Cardiac Toxicity and the Effects of c-GAS/STING Signaling

Purpose/Objective(s) The mechanism of late cardiac toxicity after radiation treatment is not well understood, and the ability to evaluate and predict this toxicity would be of great clinical value. We sought to identify radiomic features of cardiac MRI that were associated with cardiac toxicity after radiation treatment in wild type mice and a c-GAS/STING knockout model that has previously been shown to be resistant to radiation induced cardiac toxicity. Materials/Methods All protocols were approved by our institution's animal care and use committee. Cardiac irradiation was delivered to adult wild type C57BL/6 and commercially available CGAS−/- strains using a precision small animal irradiator. At 28 and 84 days after treatment, cardiac MRI was acquired with retrospective gating. The heart was segmented using open-source software. Gabor edge features, which are directionally sensitive edge detectors, were extracted for each segmented voxel using an angle of 90° and bandwidth of √2, which roughly corresponds to the voxel spacing in the MR images. The Gabor edges strengths were summarized within heart and left ventricle using first order (mean, standard deviation, skewness, and kurtosis) features. Two-tailed T tests were used to compare features between radiation treatment versus sham treatment along with the 95% confidence intervals (CI) of the difference between the group means. Results A total of 42 MRI scans were analyzed and features in the left ventricle myocardium were found to be associated with irradiation. There were significant differences in Gabor skewness (P = 0.037, CI 0.015 to 0.46) and Gabor kurtosis (P = 0.034, CI 0.13 to 3.0) in irradiated compared to sham treated wild type mice. There was no significant difference in Gabor mean edges (P = 0.060, CI -4.1 to 0.091) or Gabor SD (P = 0.25, CI -4.3 to 1.2) after irradiation. In the radioresistant CGAS−/−strain, only Gabor skewness showed a significant difference in irradiated versus sham treated mice (P = 0.007, CI 0.14 to 0.72). Conclusion We identified Cardiac MRI features that were associated with radiation induced damage. These may represent structural and/or functional changes in the left ventricle as a result of radiation induced inflammation and fibrosis. In this preliminary study, it is notable that only one of the two features associated with irradiation in wild type mice was significant in the radioresistant CGAS−/−strain. Further studies are planned to determine how these imaging features correlate with inflammation, fibrosis, and functional impairment of the heart after radiation treatment. In addition to better understanding the physiology of radiation induced cardiac toxicity, MRI radiomic analysis after cardiac exposure to radiation could be explored for clinical application.