PROJECT SUMMARY The U.S. Preventative Task Force found current ultrasound-based screening methods unreliable, causing unnecessary biopsies and failing to detect clinically significant Prostate Cancer (PCa) in patients with an elevated prostate-specific antigen (PSA). Millions of men in the U.S. alone are currently at elevated risk for PCa, but there are no effective alternatives for screening. Although MRI as a second-line screening and screening of high-risk men is gradually increasing, MRI sensitivity and specificity are currently inadequate for large-scale clinical use. Thus, there is a critical need for new and more accurate non-invasive approaches to guide the biopsies for confirming PCa. Quantitative MRI Solutions (QMIS), LLC has developed MR Virtual Pathology of the Prostate (MVP2) – a new quantitative MRI analysis and interpretation software tool for PCa screening and diagnosis. MVP2 uses compartmental analysis of hybrid-multidimensional MRI (HM-MRI) data to quantify volume fractions of three tissue spaces: lumen, stroma, and epithelium. This provides novel HM-MRI-based markers of PCa as high epithelial and low stromal and luminal fractions indicate PCa. In our previously funded NCI Phase I STTR, we accomplished all technical and logistical R&D goals. Specifically, we successfully developed and optimized the underlying compartment model to maximize agreement between MVP2 and the gold standard quantitative histology as well as evaluation of tissue composition by expert pathologists. We demonstrated the accuracy of MVP2 compared with clinical evaluation based on Prostate Imaging Reporting and Data System (PIRAD). In addition, we developed and tested a user-friendly interface for the efficient execution of our software. Our software solution is consistent with FDA requirements. The outcome of Phase I is the proven feasibility of MVP2 software for clinical screening and diagnosis of PCa. The goals of this Phase II proposal include a) ensure successful commercialization at scale by developing and testing a cloud-based MVP2 that works with leading MRI scanner brands, b) demonstrate the clinical efficacy of MVP2 for guiding biopsy via multicenter clinical trial, and c) demonstrate that MVP2 works with scanners from the 3 major manufacturers. The results from Phase II will provide strong evidence for the clinical efficacy of PCa screening with MVP2’. This will make QMIS highly competitive in the vast market for PCa screening. MVP2 will help to improve outcomes for millions of men at risk of PCa, leading to reduced misdiagnosis and overtreatment, increased survival due to early detection, and effective screening even with sub-optimal physician training.