Project Summary/Abstract Physical Sciences Inc. (PSI), in collaboration with the Department of Radiology at Brigham and Women's Hospital (BWH), proposes to develop an automated Smart Multi-grid-guidance Template (SMT) technology that will enable magnetic resonance imaging (MRI)-guided transperineal focal therapy improvement of prostate cancer (PCa). Focal therapy that targets localized PCa lesions is a growing therapeutic option for PCa patients with unifocal, low- and intermediate-risk cancer. Various energy therapy modalities, such as cryoablation, laser ablation, radiofrequency ablation, high-intensity focused ultrasound, have been clinically investigated with regards to improving post-treatment preservation of sexual and urinary function while focally treating PCa. Although these PCa focal therapy modalities have widely been utilized in conjunction with the imaging- guided approaches for precise localization of PCa lesions, accurate placement of the therapy needles within the PCa lesions remains a major challenging problem in improving the PCa therapy success rate. Therefore, there is a clinical need for a technology that can provide highly accurate placement of multiple therapy needles onto the targeted PCa lesions during focal therapy. During Phase I, PSI/BWH team will focus on the validation of the potential impact of the SMT system on focal cryoablation therapy. A preclinical prototype of the SMT system will be developed, optimized on a prostate phantom, and then its accuracy for needle placement will be tested ex vivo on excised animal prostate glands. Additionally, its capability to provide real- time needle monitoring and accurate placement of multiple therapy needles will be evaluated in vivo on a large animal model during MRI-guided focal cryoablation procedures. Based on the Phase I results and conclusions, a robust SMT system with improved performance for clinical use in various focal therapy modalities will be proposed to be developed and validated on human patients in Phase II.