Advanced Imaging Tools to Assess Cancer Therapeutics in Pediatric Patients Imaging tests are essential for cancer diagnoses in children. However, computed tomography (CT) and positron emission tomography (PET)/CT are associated with considerable radiation exposure. Several large population studies have demonstrated that cumulative radiation doses from CT scans significantly increase the risk of children developing leukemia, thyroid cancer, and brain cancer later in life. Thus, there is an urgent need to reduce the radiation exposure of children caused by medical imaging procedures. To this end, we have developed a radiation-free imaging test for pediatric tumor staging, based on advanced whole body diffusion-weighted magnetic resonance imaging (WB-DW MRI) technology. Our team was the first to integrate tumor physiology information (proton diffusion) with an MRI technique for anatomical orientation (nanoparticle- enhanced T1-weighted MRI), based on the concept of integrated PET/CT scans (Lancet Oncology). While DW MRI has demonstrated high sensitivity and specificity for cancer detection, the value of DW MRI for cancer therapy monitoring in children has not yet been extensively studied. Current approaches for assessing tumor therapy responses in children often measure changes in tumor metabolism using PET after the injection of radioactive glucose (18F-FDG). Previous comparisons of WB-DW MRI and 18F-FDG PET for cancer therapy monitoring have been inconclusive, possibly because the scans were not obtained at the same time. Thus, apparent differences may be due to differences in the timing of the scan. We are in a unique position to address this problem by simultaneously measuring therapy-induced changes in tumor metabolism and diffusion in children. These measurements have only recently become possible due to novel integrated PET/MRI technology, which is available at our pediatric hospital. The overall goal of our project is to compare the diagnostic value of DW MRI with that of 18F-FDG PET-based imaging tests for tumor therapy response assessment in children with cancer. In our pursuit of an improved and immediately clinically applicable approach for a minimally invasive imaging test, we will first apply artificial intelligence algorithms to develop ultra-low-dose 18F-FDG PET/MR scans. Next, we will determine the value of ultra-low- dose 18F-FDG PET and DW-MRI scans for monitoring tumor response to classical chemotherapy: We will determine which pediatric tumor type should be monitored with 18F-FDG PET only, DW-MRI only or a combined approach. Finally, we will determine the value of ultra-low-dose 18F-FDG PET and advanced DW- MRI techniques for monitoring tumor response to immunotherapies. Both radiation-free WB-DW MRI and ultra- low-dose 18F-FDG PET/MRI entail significantly less radiation exposure than traditional 18F-FDG PET/CT scans. The results of this project will yield customized cancer therapy response assessments for children with substant...