The Pixelated Emission Detector for RadiOisotopes (PEDRO) is a hybrid imaging system designed for the measurement of single photon emission from small animal models. The proof-of-principle device consists of a Compton-camera situated behind a mechanical collimator and is intended to provide optimal detection characteristics over a broad spectral range, from 30 keV to 511 keV.An automated routine has been developed for the optimization of the mechanical collimator which consists of pinholes and open slits. The optimization was tested with a Geant4 model of the experimental prototype. The data were blurred with the expected position and energy resolution parameters and a Bayesian interaction ordering algorithm was applied. The results show that the optimization technique allows the large-area slits to sample fully the primary field of view (FoV). The slits were found to provide truncation of the back-projected cones of response and also an increase in the success rate of the interaction ordering algorithm. These factors resulted in an increase in the contrast and signal-to-noise ratios of the reconstructed image estimates.Index Terms-Compton scattering enhancement, multiple pinhole, PEDRO.