Light crosstalk between optically separated elements of an 8 ×8 lutetium-yttrium oxyorthosilicate (LYSO) scintillation crystal matrix has been studied. The investigation was motivated by a desire to optimize the performance of the Small Animal Fast Insert for MRI (SAFIR) collaboration’s forthcoming SAFIR-II Positron Emission Tomography (PET) system. Including the originally devised inter-crystal optical separation layer comprising bonded 3M Enhanced Specular Reflector (ESR) foils, a total of four different optical separation layers have been evaluated. The alternative options included additional aluminum separators sandwiched between ESR foils, barium sulfate powder coatings of the crystals paired with interjacent ESR foils, and non-bonded ESR foils. Any other differences in materials, manufacturing, assembly and readout electronics have, to the best of our knowledge, been precluded. To quantify light crosstalk for a 511keV photon, the number, distribution, and energy of all incidental hits registered in 18 F measurements at activities