Mapping radiation injury and recovery in bone marrow using ¹⁸F-FLT PET/CT and USPIO-MR imaging in a rat model

Abstract

We present and test the use of multimodality imaging as a topological tool to map the amount of the body exposed to ionizing radiation and the location of exposure, which are important indicators of survival and recovery. To achieve our goal, PET/CT imaging utilizing 3’-deoxy-3’-¹⁸F-fluorothymidine (¹⁸F-FLT) was used to measure cellular proliferation in bone marrow (BM), while MR imaging using ultra-small superparamagnetic iron oxide (USPIO) particles provided noninvasive information on radiation-induced vascular damage. Methods: Animals were x-ray irradiated at a dose of 7.5 Gy with one of three radiation schemes: whole body irradiation (WBI), half body shielding (HBS), or one leg shielding (1LS), and were imaged repeatedly. The spatial information from the CT scan was used to segment the region corresponding to BM from the PET scan using algorithms developed in-house, allowing for quantification of proliferating cells, and BM blood volume was estimated by measuring the changes in the T2 relaxation rates (ΔR2) collected from MR scans. Results: ¹⁸F-FLT PET/CT imaging differentiated irradiated from unirradiated BM regions. Two days post irradiation, proliferation of 1LS animals was significantly lower than sham (P = 0.0001 femurs; P <0.0001 tibias) and returned to sham levels by day 10 (P = 0.6344 femurs; P = 0.3962 tibias). The degree of shielding affected proliferation recovery, showing an increase (P = 0.0310 femurs; P = 0.5832 tibias) in the irradiated BM of HBS animals when compared to 1LS. MR imaging of irradiated spines detected radiation-induced BM vascular damage, measured by the significant increase in ΔR2 two days after WBI (P = 0.0022) and HBS (P = 0.0003) with a decreasing trend of values, returning to levels close to baseline over 10 days. Our data was corroborated using gamma counting and histopathology. Conclusion: We demonstrated that ¹⁸F-FLT PET/CT and USPIO-MRI are valuable tools in mapping regional radiation exposure and the effects of radiation on BM. Analysis of the FLT signal allowed for a clear demarcation of exposed BM regions and elucidated the kinetics of BM recovery, while USPIO-MRI was used to assess vascular damage and recovery.