Abstract: Positron emission tomography (PET) is a widely used technique in medical imaging and in studying small animal models of human disease. In the conventional approach, the 511 keV annihilation photons emitted from a patient or small animal are detected by a ring of scintillators such as LYSO read out by arrays of photodetectors. Although this has been successful in achieving similar to 5 mm FWHM spatial resolution in human studies and similar to 1 mm resolution in dedicated small animal instruments, there is interest in significantly improving these figures. Silicon, although its stopping power is modest for 511 keV photons, offers a number of potential advantages over more conventional approaches including the potential for high intrinsic spatial resolution in 3D. To evaluate silicon in a variety of PET “magnifying glass” configurations, an instrument was constructed that consists of an outer partial-ring of PET scintillation detectors into which various arrangements of silicon detectors are inserted to emulate dual-ring or imaging probe geometries. Measurements using the test instrument demonstrated the capability of clearly resolving point sources of Na-22 having a 1.5 mm center-to-center spacing as well as the 1.2 mm rods of a F-18-filled resolution phantom. Although many challenges remain, silicon has potential to become the PET detector of choice when spatial resolution is the primary consideration. (C) 2012 Elsevier B.V. All rights reserved.