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One of the most promising high resolution PET detector designs comprises an array of small, optically isolated scintillator crystals each coupled to an independent photosensor, such as an avalanche photodiode (APD). However, cross-talk between crystals (due to Compton scatter, photoelectron escape, or incomplete optical isolation) can significantly degrade performance, and is expected to increase as crystals become narrower to improve spatial resolution. Various measures of cross-talk have been determined for different configurations of 4x8 blocks of 2 mm × 2 mm lutetium oxyorthosilicate (LSO) crystals coupled to matched Hamamatsu APD arrays. Results indicate that ignoring crosstalk signals could lead to a ∼30% loss in coincidence sensitivity for a tomograph using these detectors, and a decrease in energy resolution of ∼2 percentage points. Spatial and time resolution would not be significantly affected with most practical front-end architectures.