Project Summary One of the central limitations of PET/MRI is the lack of accurate means of attenuation correction, which leads to inaccurate and inconsistent quantification of radiotracer uptake. The inconsistency of PET quantification prevents the widespread adoption of PET/MRI in clinical trials, where a precise and reproducible measurement of radiotracer uptake is required. We propose in this application to develop a standard methodology to evaluate MR based attenuation correction techniques and the related PET quantitation accuracy in order to qualify PET/MRI scanners for clinical trials and clinical work. This work will be done in three specific aims. First, we will evaluate materials and create a physical phantom for evaluation of MR based attenuation correction techniques. We will subsequently validate the phantom using a patient study to demonstrate that we can accurately estimate deviations of measured activity using the PET/MRI phantom. Finally, we will harmonize the reconstruction parameters on the two available PET/MRI scanners and evaluate the reproducibility of the quantitative accuracy across 12 PET/ MRI sites split between the two PET/MRI manufacturers. Finally we will incorporate the PET/MRI harmonization data into a global harmonization study that includes both PET/MRI and PET/CT. Through the work described, we aim to create a standardized approach to evaluate the accuracy of PET quantification in the setting of PET/MRI. A standardized methodology will incent vendors to develop attenuation correction methods that result in more consistent uptake estimates across systems, and the ability to qualify scanners will help the adoption of PET/MRI into clinical trials and clinical care.