Abstract: The development of novel detection devices and systems such as the AX-positron emission tomography (PET) demonstrator often introduce or increase the measurement of atypical coincidence events such as inter-crystal scattering (ICS). In more standard systems, ICS events often go undetected and the small measured fraction may be ignored. As the measured quantity of such events in the data increases, so too does the importance of considering them during image reconstruction. Generally, treatment of ICS events will attempt to determine which of the possible candidate lines of response (LoRs) correctly determine the annihilation photon trajectory. However, methods of assessment often have low success rates or are computationally demanding. In this investigation alternative approaches are considered. Experimental data was taken using the AX-PET prototype and a NEMA phantom. Three methods of ICS treatment were assessed-each of which considered all possible candidate LoRs during image reconstruction. Maximum likelihood expectation maximization was used in conjunction with both standard (line-like) and novel (V-like in this investigation) detection responses modeled within the system matrix. The investigation assumed that no information other than interaction locations was available to distinguish between candidates, yet the methods assessed all provided means by which such information could be included. In all cases it was shown that the signal to noise ratio is increased using ICS events. However, only one method, which used full modeling of the ICS response in the system matrix-the V-like model-provided enhancement in all figures of merit assessed in this investigation. Finally, the optimal method of ICS incorporation was demonstrated using data from two small animals measured using the AX-PET demonstrator.