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

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 with 3?-deoxy-3?-18Ffluorothymidine (¹⁸F-FLT) was used to measure cellular proliferation in bone marrow (BM), whereas MRI using ultra-small superparamagnetic iron oxide (USPIO) particles provided noninvasive information on radiationinduced vascular damage. Methods: Animals were x-ray-irradiated at a dose of 7.5 Gy with 1 of 3 radiation schemes-whole-body irradiation, half-body shielDing (HBS), or 1-leg shielDing (1LS)-and 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 (DR2) collected from MR scans. Results: ¹⁸F-FLT PET/CT imaging differentiated irradiated from unirradiated BM regions. Two days after irradiation, proliferation of 1LS animals was significantly lower than sham (P 5 0.0001, femurs; P , 0.0001, tibias) and returned to sham levels by day 10 (P 5 0.6344, femurs; P5 0.3962, tibias). The degree of shielDing affected proliferation recovery, showing an increase in the irradiated BM of the femurs, but not the tibias, of HBS animals when compared with 1LS (P 5 0.0310, femurs; P 5 0.5832, tibias). MRI of irradiated spines detected radiation-induced BM vascular damage, measured by the significant increase in DR2 2 d after wholebody irradiation (P 5 0.0022) and HBS (P 5 0.0003) with a decreasing trend of values, returning to levels close to baseline over 10 d. Our data were corroborated using ?-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 ¹⁸F-FLT signal allowed for a clear demarcation of exposed BM regions and elucidated the kinetics of BM recovery, whereas USPIOMRI was used to assess vascular damage and recovery.