Radionuclide-guided intraoperative probes increase the specificity of tissue biopsies, enable minimal- access incisions, reduce inpatient hospital utilization, and contribute to improved patient recovery. At present, most such probes on the market are non-imaging, and provide no ancillary information of surveyed areas, such as clear delineations of malignant tissues. Our goal is to develop a revolutionary new imaging probe, the Imaging Beta ProbeTM (IBPTM), intended for rapid localization of lesions by sensing gamma rays, followed by real-time high-sensitivity imaging of short-range beta particles or positrons. This ergonomically designed probe will be small and easy to use during surgery, and is made possible by the recent development of position- sensitive solid-state photomultiplier (PS-SSPM) and hybrid scintillation technologies at RMD. The probe will provide continuous real-time audio and/or video feedback of emissions from surveyed areas to the surgeon for rapid and accurate delineation and precise excision of lesions, with minimal sacrifice of surrounding healthy tissue. After excision of suspect tissue, the IBPTM will allow the surgeon to check the tumor bed and margins for any remaining cancerous and pre-cancerous tissue, fine tumors or other tissues (e.g., endometrial) capable of uptake of the administered tracer, that are otherwise obscured by background radiation. Our motivation in pursuing our proposed Imaging Beta Probe design is that it will provide the first radical change in probe technology in decades and, most importantly, significant improvement in and broadening of the clinical capabilities of intraoperative and external diagnostic probes. Development of this technology provides an imaging tool for surgeons to detect PET-positive lesions intraoperatively, which will advance their ability to confirm data provided by PET scans with biopsy material. Furthermore, these tools may allow a surgeon to perform a PET-guided exploration and therapeutic excision of a small lesion that would otherwise be undiscovered by conventional exploration or treated by a harsh empiric regimen of chemotherapy or radiation.