PROJECT SUMMARY While the technological enterprise of magnetic resonance imaging (MRI) generates a host of biomarkers of the tumor environment, in particular for breast cancer, precious few (and typically only first-order markers) have been tested beyond single site studies with single workflow processing. To address both the need for advanced tissue characterization and multi-site translation, we propose a multi-site study of intravoxel incoherent motion (IVIM) MRI in breast cancer to determine its maximum translational prognostic benefit. The IVIM model, which includes separate markers of tissue cellularity, vascular volume, and micro-vascular flow, has been successfully applied in a range of cancers, including breast cancer by the project teams of this proposal. This project will determine inherent variability of the technique with hardware variation (3 vendors) and software platforms (6 packages), in a 5 site retrospective analysis of clinical breast cancer IVIM data. We will then conduct a prospective two-site IVIM longitudinal study of patients undergoing neoadjuvant chemotherapy to determine the best pre- or mid-treatment biomarkers to predict therapeutic response. At each stage, performance will be evaluated both within each site and in the combined cohort, with the goal of identifying biomarkers that are both useful and broadly translatable.