Good spatial resolution and high sensitivity are required for detectors to be used for most of the bio-medical research and application (small animal imaging, detection of small tumors,). In this paper we report on parameter optimization of single photon gamma rays detectors. Simulations and measurements were performed for designing and building detectors for early detection of small tumors in breast and in small animal imaging. Critical parameters are: Contrast and Signal to Noise Ratio (SNR). Intrinsic performances (spatial resolution, pixel identification etc.) were optimized first. Arrays of scintillators (NaI(Tl)) of different pixel pitch (down to the present technological limits for NaI(Tl) arrays fabrication (pitch of 2 × 2 mm2,1.5 × 1.5 mm2 and 1.2 × 1.2 mm 2)) were coupled to arrays of PSPMTs with two anode readout element dimensions (6 × 6 mm2 and 3 × 3 mm2). Detectors having Field Of View of 100 × 100 mm2 and 150 × 200 mm2 were designed and built. An electronics system for reading out all the anode pad signals has been designed and constructed. Finally the collimation technique was considered. The limits of the coded aperture option have been studied. Preliminary results of these studies are presented.