Advances in ultrasound (US) imaging have developed from improved electronics, software, miniaturization, transducer design, fabrication, and construction. These advances have lead to the development of important and commonplace clinical modalities including intracavitary, endoluminal and intravascular US. Trans-urethral ultrasound (TUUS) is an unrealized clinical modality worthy and ready for development. The major goal of this research is to develop and validate a TUUS device to improve imaging and image guided therapy for prostate diseases. Significant preliminary results have demonstrated the potential of TUUS for enhancing image guidance of prostate cancer therapy. Specifically, the use of TUUS to improve guidance of radioactive seed implantation, also known as permanent prostate brachytherapy, has been demonstrated. The research plan includes Specific Aims in the following areas: (1) design, build and test TUUS catheters specifically for prostate applications, (2) evaluate and optimize TUUS as the preferred prostate imaging modality for guidance of minimally invasive prostate cancer therapy, particularly permanent prostate brachytherapy, and (3) develop and evaluate TUUS as a diagnostic imaging tool. The research team includes collaborators from Mayo Clinic, Siemens AG, Ultrasound Division, and Ascension Technology Corporation (ATC). Significant prior efforts of the team include research and commercial development of an intracardiac ultrasound catheter and 3D image processing software. Design specifications for the TUUS catheter are based on clinical results from the Mayo Clinic. Design and fabrication of the ultrasound catheters will be completed by Siemens. Magnetic positional tracking devices and sensors to be included in the catheter allowing 3D US will be provided by ATC and integrated into the device by Siemens. Laboratory and clinical evaluation of the device will be conducted at the Mayo Clinic by a multidisciplinary team of scientists and clinicians. Clinical tests will include TUUS during permanent prostate brachytherapy and cryotherapy. Diagnostic evaluation will include imaging of patients with locally advanced prostate cancer immediately prior to prostatectomy and correlation with subsequent detailed histopathology. Successful completion of the proposed research will yield a new imaging tool with likely immediate commercial potential that significantly improves image guided prostate diagnosis, biopsy and therapy.