Project Summary Abstract The goal is to identify and characterize prostate cancer objectively and accurately using a rapid quantitative Magnetic Resonance Imaging (MRI) approach. The standard-of-care in patients being evaluated for suspicion of prostate cancer is systematic sampling of the entire gland with 12 biopsy cores, without an identified focus suspicious for cancer on imaging. Current qualitative MR images, while mostly successful in highlighting prostate cancer, may look different from scanner to scanner, or even when repeated on the same scanner. This variability adds complexity to an already subjective interpretive process of detecting cancer and discriminating between clinically significant and indolent disease. Thus, more robust and standardized MRI methods to detect and characterize clinically significant prostate cancer are needed. This project plans to address this issue with following specific aims: (1) A rapid high-resolution 3D MRF acquisition will be developed and optimized for prostate cancer assessment by innovating reduced field-of-view imaging, 3D Cartesian sampling, and advanced reconstruction in MRF. The proposal MRF acquisition will enable accurate T1 and T2 mapping over the prostate gland with an isotropic submillimeter resolution (0.8 mm3) in an acquisition time of less than 5 minutes. (2) Contrast-weighted images synthesized using MRF-based T1 and T2 maps will replace conventional qualitative images for detecting prostate cancer. (3) MRF-based T1 and T2 with apparent diffusion coefficient will be validated to separate cancer from non-cancer and differentiate cancers with different grades. (4) Microstructural signatures of prostate cancer derived from MRF will provide information about subvoxel components (epithelium, stroma, lumen, and their volume fractions) to reveal occult cancers and enable the discrimination of different grades of cancer. This project will advance prostate imaging by providing reproducible and repeatable non-invasive quantitative imaging metrics. These innovations will replace conventional contrast-weighted imaging with a single rapid high-resolution standard MRF protocol, provide an objective identification of prostate cancer and grading, and improve the classification of prostate cancer using microstructural signatures, thus reducing unnecessary biopsies and facilitating appropriate treatment selection.