The applicants proposed to improve the performance and lower the cost of positron emission tomography (PET) for clinical and research applications in oncology. A prototype PET has been developed. This tomographic system has achieved a high resolution of 2.8 mm, compared to the 4.6 mm currently available in the highest resolution human PET camera. The camera has convertible modes of operation: (a) A high sensitivity brain and animal mode, (b) a whole-body tumor localization mode and (c) a breast mode with 8x the sensitivity of regular PET. This camera uses a higher resolution and lower cost PET detector design, which, when coupled with the convertible geometry, has the potential of lowering the high PET production cost by 30%. The high-sensitivity, high-resolution, small-animal mode is for evaluating new experimental therapies and new diagnostic ligands and for extending our understanding of cancer through studies of animal tumor models. The high-resolution, high-sensitivity brain mode would be useful for detecting small lesions, for a more sensitive differentiation of recurring tumors from necrosis, and for studies of small structures in the brain. The whole-body mode would be useful for tumor localization, cancer staging, and cardiac functional studies. The breast mode, with 2.8 mm resolution and 8x, the detection sensitivity improves the specificity and sensitivity of breast cancer diagnosis, which can reduce unnecessary biopsy for women with false-positive mammograms. It is also useful for diagnosing early/small breast tumors, especially in younger, high-risk women and women with implants, which present difficulties for x-ray mammography. The applicants propose to: (1) Quantitatively evaluate the prototype PET for human cancer application under realistic clinical conditions. (2) Demonstrate on the experimental PET an improved detector design which may improve human-PET resolution to 2.4 mm together with higher sensitivity. (3) Implement and test a novel position -decoding electronics that resolves signal-pileups in detectors, so that the camera can operate at Sx higher count-rates (or injected dose) with minimum count-loss and resolution-loss. (4) Use the prototype as an experimental imaging platform to find the optimal septa design for difficult 3-D image acquisition (traditionally septa-less). Optimal septa improve lesion detection by balancing sensitivity and scatter/accidental noises. (5) Develop and test a new coincidence acquisition method that can automatically change the energy thresholds and timing window to minimize scatter and accidental fractions during a scan. The method can dynamically maximize image quality as imaging condition changes when the camera is scanning different parts of the body. The novel PET imaging technology described in aims (2-5) is applicable to any existing PET camera design. The experimental PET platform provides a unique flexible way to conclusively test and demonstrate these novel PET imaging concepts in the form of actual images