The performances of standard gamma-cameras are limited by the well-known trade-off between spatial resolution and sensitivity resulting from the collimator. To overcome this limitation, we have previously proposed a new approach named HiSens, which consists in the association of a pixelated CZT detector, new collimation geometry and dedicated reconstruction algorithms. Two maj or characteristics of the CZT detector are taken advantage of in this architecture: the availability of the depth of interaction (DOl) information and the fine pixelization.In this paper, we consider a configuration using a high sensitivity collimator: the septa height· of the collimator is reduced to ensure a gain in efficiency by a factor of five compared with the Anger Camera (10-4 efficiency). Using DOl information, CZT detector is divided in several virtual layers providing distinct images, which can be combined within a dedicated OSEM reconstruction scheme. Moreover, two possible pixelizations of the CZT detector are studied: one and four pixels per collimator hole. The ultimate aim of this study is to increase the global system efficiency while preserving the spatial resol ution.A complete evaluation of the performance of this architecture has been performed, based on a simple analytical model, on Monte Carlo simulations of the system, and on experimental data.Simulation results show that CZT detector over-pixelization improves the contrast without introducing additional noise. They are confirmed by the experimental validation: contribution of the detector over-pixelization is crucial for improved image quality.