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Single Photon Emission Computed Tomography(SPECT)suffers limited detection efficiency and spatial resolution due to the need for collimators and un-direct conversion of scintillation detectors.Various materials and configurations of collimators and detectors have been investigated in many years.The main thrust of our study is to quantitatively analyze how geometry and materials of the pixel-geometry-matching(PGM)collimators and the notably direct-conversion solid-state Cadmium Zinc Telluride(CZT)detectors impact the essential merits of the front-end system using Geant4 Monte Carlo simulations.The large-detection-area(20.48mm x 20.48mm)CZT-based detectors,being currently built for our project,with a small pixel pitch(1.6 mm)can greatly improve the sensitivity as well as the energy resolution than the conventional ones,and such enable multi-tracers imaging.The PGM collimator has a higher intrinsic resolution due to the small pixels and thus a better spatial resolution and its made in tungsten alloy to decrease the rate of penetration compared with the lead-based and reduce the manufacturing cost compared with the tungsten-based.The energy-independent SPECTthat will not require changes of collimators for different photon energies can be realized,at least for potential applications(breast,brain,and prostate)of small volume SPECT applications targeted by the proposed imaging system.Simultaneous multi-isotope imaging allows the exploration of various molecular and physiological functions under the identical conditions.The results of simulated studies for sensitivity,spatial resolution,scatter,penetration,uniformity and energy spectra,crosstalk in various settings of design parameters are shown to test and verify the potential performancesof such collimator-detector system.The preliminary outcomes are very encouraging and demonstrate the potential for improving performances of the energy-independent cameras using a combination of CZT detectors and pixel-geometry-matching collimators.